Abstract: The main objective of present investigation is to formulate the sustained release
tablet of Rosiglitazone Maleate using 32 factorial design. Rosiglitazone Maleate, an oral antidiabetic
agent. The SR tablets of Rosiglitazone Maleate were prepared employing different
concentrations of HPMCK15M and Carboplol934P in different combinations as a rate
retardants by Direct Compression technique using 32 factorial design. The quantity/
concentration of Polymers , HPMCK15M and Carboplol934P required to achieve the desired
drug release was selected as independent variables, X1 and X2 respectively whereas, time
required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were
selected as dependent variables. Totally nine formulations were designed and are evaluated
for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it
was concluded that all the formulation were found to be with in the Pharmacopoeial limits
and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic
models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r)
were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 25%
HPMCK15M and 20% Carboplol934P, is the most similar formulation (similarity factor
f2=93.1376, dissimilarity factor f1= 1.7642 & No significant difference, t= 0.06949) to
marketed product (AVANDIA). The selected formulation (F5) follows Higuchi’s kinetics,
and the mechanism of drug release was found to be Fickian Diffusion (n= 0.417).
ABSTRACT
The main objective of present investigation is to formulate the sustained release tablet of Metoprolol Succinate
using 32 factorial design. Metoprolol Succinate, is a selective β1blocker, to treat Hypertension & Heart Failure. The
SR tablets of Metoprolol Succinate were prepared employing different concentrations of HPMCK15M and
HPMCK100M in different combinations as a rate retardants by Direct Compression technique using 32 factorial
design. The quantity of rate retarders, HPMCK15M and HPMCK100M required to achieve the desired drug release
was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution
(t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Totally nine formulations were
designed and are evaluated for hardness, friability, thickness, % drug content, In-vitro drug release. From the
Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the Invitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like
intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 10% HPMCK15M and 10%
HPMCK100M, is the most similar formulation (f2=92.38 & No significant difference, t= 0.0216) to marketed
product (Metocard). The selected formulation (F5) follows Higuchi’s kinetics, the mechanism of drug release was
found to be Super case II transport (Non-Fickian, n= 0.981).
The main objective of present investigation is to formulate the floating tablets of
Ranitidine.HCl using 32 factorial design. Ranitidine.HCl, H2-receptor antagonist belongs to
BCS Class-III. The Floating tablets of Ranitidine.HCl were prepared employing different
concentrations of HPMCK4M and Guar Gum in different combinations as a release rate
modifiers by Direct Compression technique using 32 factorial design. The concentration of
Polymers , HPMCK4M and Guar Gum required to achieve desired drug release was selected
as independent variables, X1 and X2 respectively whereas, time required for 10% of drug
dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables.
Totally nine formulations were designed and are evaluated for hardness, friability, thickness,
% drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all
the formulation were found to be within the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated.
Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed
polynomial equations were verified by designing 2 check point formulations(C1, C2).
According to SUPAC guidelines the formulation (F5) containing combination of 22.5%
HPMCK4M and 22.5% Guar Gum, is the most similar formulation (similarity factor f2=85.01,
dissimilarity factor f1= 15.358 & No significant difference, t= 0.169) to marketed product
(ZANTAC). The selected formulation (F5) follows Higuchi’s kinetics, and the mechanism of
drug release was found to be Non-Fickian Diffusion (n= 0.922).
ABSTRACT
The main objective of present research work is to formulate the of Domperidone Maleate floating tablets.
Domperidone Maleate, an antiemetic and a prokinetic agent belongs to BCS Class-II and Indicated for treatment of
upper gastrointestinal motility disorders by blocking the action of Dopamine. The Floating tablets of Domperidone
Maleate were prepared employing different concentrations of HPMCK4M and Guar Gum in different combinations
as a release rate modifiers by Direct Compression technique using 32 factorial design. The concentration of
HPMCK4M and Guar Gum was selected as independent variables, X1 and X2 respectively whereas, time required
for drug dissolution t10%, t50%,t75%,t90%were selected as dependent variables. Totally nine formulations were designed
and are evaluated for hardness, friability, thickness, Assay, Floating Lag time, In-vitro drug release. From the
Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like
intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 18.75% HPMCK4M and
18.75% Guar Gum, is the most similar formulation (similarity factor f2=89.03, dissimilarity factor f1= 11.539& No
significant difference, t= 0.169) to marketed product (DOMSTAL OD). The selected formulation (F5) follows
Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.925).
Keywords: Domperidone Maleate, 32Factorial Design, Gastro retentive Floating Tablet, HPMCK100M, Sodium
bicarbonate, Floating Lag Time, SUPAC, Non-Fickian Diffusion Mechanism.
ABSTRACT
The main objective of present investigation is to formulate the sustained release tablet of Zidovudine using 32
factorial design. Zidovudine, antiretroviral drug belongs to BCS Class I. The SR tablets of Zidovudine were
prepared employing different concentrations of Carboplol974P and Xanthan gum in different combinations as a
rate retardants by Direct Compression technique using 32 factorial design. The quantity of rate retarders,
Carboplol974P and Xanthan gum required to achieve the desired drug release was selected as independent
variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%)
and 90% (t90%) were selected as dependent variables. Totally nine formulations were designed and are evaluated
for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it was concluded that all
the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all
formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) &
regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations(C1, C2). According to
SUPAC guidelines the formulation (F5) containing combination of 5% Carboplol974P and 5% Xanthan gum, is the
most similar formulation (f2=85.04 & No significant difference, t= 0.20046) to marketed product (Retrovir). The
selected formulation (F5) follows Higuchi’s kinetics, the mechanism of drug release was found to be Case-II
transport or typical Zero order release (Non-Fickian, n= 0.915).
Abstract
The main objective of present research work is to formulate the floating tablets of atenolol using 32 factorial design. Atenolol, β-blocker belongs to Biopharmaceutical Classification System Class-III. The floating tablets of atenolol were prepared employing different concentrations of hydroxypropyl methylcellulose (HPMC) K15M and sodium bicarbonate in different combinations by direct compression technique using 32 factorial design. The concentration of HPMC K15M and sodium bicarbonate required to achieve desired drug release was selected as independent variables, X1 and X2, respectively, whereas time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%), and 90% (t90%) were selected as dependent variables. Totally, nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, floating lag time, in vitro drug release. From the results, concluded that all the formulation were found to be within the pharmacopoeial limits and the in vitro dissolution profiles of all formulations were fitted into different Kinetic models, the statistical parameters like intercept (a), slope (b) and regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed polynomial equations was verified by designing 2 checkpoint formulations (C1, C2). According to SUPAC guidelines the formulation (F8) containing combination of 25% HPMC K15M and 3.75% sodium bicarbonate, is the most similar formulation (similarity factor f2 = 87.797, dissimilarity factor f1 = 2.248 and no significant difference, t = 0.098) to marketed product (BETACARD). The selected formulation (F8) follows Higuchi’s kinetics, and the mechanism of drug release was found to be non-Fickian diffusion (n = 1.029, Super Case-II transport).
ABSTRACT
The main objective of present research work is to formulate the floating tablets of Carvedilol Phosphate using 32 factorial design. Carvedilol Phosphate, non-selective α1-β1-blocking agent belongs to BCS Class-II and Indicated for treatment of Hypertension/moderate Heart Failure. The Floating tablets of Carvedilol Phosphate were prepared employing different concentrations of HPMCK100M and Sodium bicarbonate in different combinations by Direct Compression technique using 32 factorial design. The concentration of HPMCK100M and Sodium bicarbonate required to achieve desired drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Totally nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F8) containing combination of 25% HPMCK100M and 3.75% Sodium bicarbonate, is the most similar formulation (similarity factor f2=88.801, dissimilarity factor f1= 2.250 & No significant difference, t= 0.095) to marketed product (CARDIVAS). The selected formulation (F8) follows Higuchi’s kinetics, and the mechanism
This document describes the development and evaluation of carvedilol phosphate gastroretentive floating tablets using a 32 factorial design. Carvedilol phosphate is a drug that belongs to BCS Class II and is indicated for hypertension and heart failure. Floating tablets were prepared using varying concentrations of guar gum and sodium bicarbonate as polymers to control the release of the water soluble drug. Nine formulations were designed and evaluated for properties like drug content, floating lag time, and in vitro drug release using kinetic models. The results showed that all formulations met pharmacopeial standards and formulation F8 containing 25% guar gum and 3.75% sodium bicarbonate best matched the marketed product with respect to drug release.
ABSTRACT
The main objective of present investigation is to formulate the sustained release tablet of Metoprolol Succinate
using 32 factorial design. Metoprolol Succinate, is a selective β1blocker, to treat Hypertension & Heart Failure. The
SR tablets of Metoprolol Succinate were prepared employing different concentrations of HPMCK15M and
HPMCK100M in different combinations as a rate retardants by Direct Compression technique using 32 factorial
design. The quantity of rate retarders, HPMCK15M and HPMCK100M required to achieve the desired drug release
was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution
(t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Totally nine formulations were
designed and are evaluated for hardness, friability, thickness, % drug content, In-vitro drug release. From the
Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the Invitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like
intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 10% HPMCK15M and 10%
HPMCK100M, is the most similar formulation (f2=92.38 & No significant difference, t= 0.0216) to marketed
product (Metocard). The selected formulation (F5) follows Higuchi’s kinetics, the mechanism of drug release was
found to be Super case II transport (Non-Fickian, n= 0.981).
The main objective of present investigation is to formulate the floating tablets of
Ranitidine.HCl using 32 factorial design. Ranitidine.HCl, H2-receptor antagonist belongs to
BCS Class-III. The Floating tablets of Ranitidine.HCl were prepared employing different
concentrations of HPMCK4M and Guar Gum in different combinations as a release rate
modifiers by Direct Compression technique using 32 factorial design. The concentration of
Polymers , HPMCK4M and Guar Gum required to achieve desired drug release was selected
as independent variables, X1 and X2 respectively whereas, time required for 10% of drug
dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables.
Totally nine formulations were designed and are evaluated for hardness, friability, thickness,
% drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all
the formulation were found to be within the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated.
Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed
polynomial equations were verified by designing 2 check point formulations(C1, C2).
According to SUPAC guidelines the formulation (F5) containing combination of 22.5%
HPMCK4M and 22.5% Guar Gum, is the most similar formulation (similarity factor f2=85.01,
dissimilarity factor f1= 15.358 & No significant difference, t= 0.169) to marketed product
(ZANTAC). The selected formulation (F5) follows Higuchi’s kinetics, and the mechanism of
drug release was found to be Non-Fickian Diffusion (n= 0.922).
ABSTRACT
The main objective of present research work is to formulate the of Domperidone Maleate floating tablets.
Domperidone Maleate, an antiemetic and a prokinetic agent belongs to BCS Class-II and Indicated for treatment of
upper gastrointestinal motility disorders by blocking the action of Dopamine. The Floating tablets of Domperidone
Maleate were prepared employing different concentrations of HPMCK4M and Guar Gum in different combinations
as a release rate modifiers by Direct Compression technique using 32 factorial design. The concentration of
HPMCK4M and Guar Gum was selected as independent variables, X1 and X2 respectively whereas, time required
for drug dissolution t10%, t50%,t75%,t90%were selected as dependent variables. Totally nine formulations were designed
and are evaluated for hardness, friability, thickness, Assay, Floating Lag time, In-vitro drug release. From the
Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like
intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 18.75% HPMCK4M and
18.75% Guar Gum, is the most similar formulation (similarity factor f2=89.03, dissimilarity factor f1= 11.539& No
significant difference, t= 0.169) to marketed product (DOMSTAL OD). The selected formulation (F5) follows
Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.925).
Keywords: Domperidone Maleate, 32Factorial Design, Gastro retentive Floating Tablet, HPMCK100M, Sodium
bicarbonate, Floating Lag Time, SUPAC, Non-Fickian Diffusion Mechanism.
ABSTRACT
The main objective of present investigation is to formulate the sustained release tablet of Zidovudine using 32
factorial design. Zidovudine, antiretroviral drug belongs to BCS Class I. The SR tablets of Zidovudine were
prepared employing different concentrations of Carboplol974P and Xanthan gum in different combinations as a
rate retardants by Direct Compression technique using 32 factorial design. The quantity of rate retarders,
Carboplol974P and Xanthan gum required to achieve the desired drug release was selected as independent
variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%)
and 90% (t90%) were selected as dependent variables. Totally nine formulations were designed and are evaluated
for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it was concluded that all
the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all
formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) &
regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations(C1, C2). According to
SUPAC guidelines the formulation (F5) containing combination of 5% Carboplol974P and 5% Xanthan gum, is the
most similar formulation (f2=85.04 & No significant difference, t= 0.20046) to marketed product (Retrovir). The
selected formulation (F5) follows Higuchi’s kinetics, the mechanism of drug release was found to be Case-II
transport or typical Zero order release (Non-Fickian, n= 0.915).
Abstract
The main objective of present research work is to formulate the floating tablets of atenolol using 32 factorial design. Atenolol, β-blocker belongs to Biopharmaceutical Classification System Class-III. The floating tablets of atenolol were prepared employing different concentrations of hydroxypropyl methylcellulose (HPMC) K15M and sodium bicarbonate in different combinations by direct compression technique using 32 factorial design. The concentration of HPMC K15M and sodium bicarbonate required to achieve desired drug release was selected as independent variables, X1 and X2, respectively, whereas time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%), and 90% (t90%) were selected as dependent variables. Totally, nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, floating lag time, in vitro drug release. From the results, concluded that all the formulation were found to be within the pharmacopoeial limits and the in vitro dissolution profiles of all formulations were fitted into different Kinetic models, the statistical parameters like intercept (a), slope (b) and regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed polynomial equations was verified by designing 2 checkpoint formulations (C1, C2). According to SUPAC guidelines the formulation (F8) containing combination of 25% HPMC K15M and 3.75% sodium bicarbonate, is the most similar formulation (similarity factor f2 = 87.797, dissimilarity factor f1 = 2.248 and no significant difference, t = 0.098) to marketed product (BETACARD). The selected formulation (F8) follows Higuchi’s kinetics, and the mechanism of drug release was found to be non-Fickian diffusion (n = 1.029, Super Case-II transport).
ABSTRACT
The main objective of present research work is to formulate the floating tablets of Carvedilol Phosphate using 32 factorial design. Carvedilol Phosphate, non-selective α1-β1-blocking agent belongs to BCS Class-II and Indicated for treatment of Hypertension/moderate Heart Failure. The Floating tablets of Carvedilol Phosphate were prepared employing different concentrations of HPMCK100M and Sodium bicarbonate in different combinations by Direct Compression technique using 32 factorial design. The concentration of HPMCK100M and Sodium bicarbonate required to achieve desired drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Totally nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F8) containing combination of 25% HPMCK100M and 3.75% Sodium bicarbonate, is the most similar formulation (similarity factor f2=88.801, dissimilarity factor f1= 2.250 & No significant difference, t= 0.095) to marketed product (CARDIVAS). The selected formulation (F8) follows Higuchi’s kinetics, and the mechanism
This document describes the development and evaluation of carvedilol phosphate gastroretentive floating tablets using a 32 factorial design. Carvedilol phosphate is a drug that belongs to BCS Class II and is indicated for hypertension and heart failure. Floating tablets were prepared using varying concentrations of guar gum and sodium bicarbonate as polymers to control the release of the water soluble drug. Nine formulations were designed and evaluated for properties like drug content, floating lag time, and in vitro drug release using kinetic models. The results showed that all formulations met pharmacopeial standards and formulation F8 containing 25% guar gum and 3.75% sodium bicarbonate best matched the marketed product with respect to drug release.
This document describes the formulation development and evaluation of simvastatin sustained release tablets. A 32 full factorial design was used to investigate the effect of two polymers, HPMCK4M and SCMC, on drug release times (t10%, t50%, t75%, t90%). Nine formulations were prepared according to the design and evaluated for properties like hardness, friability, thickness, drug content, and in-vitro drug release. Polynomial equations were developed relating the polymer concentrations to drug release times. The formulation containing 17.5% HPMCK4M and 30% SCMC (F4) showed drug release most similar to the marketed product and followed zero-order kinetics and non-Fickian diffusion mechanisms.
Objective: The purpose of present research work is to develop the sustained release formulation for Telmisartan using 32 factorial design. Telmisartan an Antihypertensive agent, nonpeptide angiotensin-II receptor (type AT1) antagonist and BCS class-II agent. Methods: Sustained Release tablet formulations of Telmisartan were prepared using different quantities of HPMCK100M and Xanthan Gum in combinations by direct compression technique. The concentration of Polymers, HPMCK100M and Xanthan gum required to achieve the drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Nine formulations were prepared and are evaluated for various pharmacopoeial tests. Results: The results reveals that all formulations were found to be with in the pharmacopoeial limits and In vitro drug release profiles of all formulations were fitted in to various Kinetic models. The statistical parameters like intercept, slope & correlation coefficient were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial equations were checked by designing 2 check point formulations (C1, C2). Conclusion: According to SUPAC guidelines formulation (F5) containing combination of 15% HPMCK100M and 15% Xanthan gum, is the most identical formulation (similarity factor f2= 90.863, dissimilarity factor f1= 1.665 & No significant difference, t= 0.03379) to marketed product (TELVAS). Best Formulation F5 follows First order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion Anomalous Transport. (n= 0.828).
This seminar discusses modified release drug delivery systems. It begins with an introduction defining modified release as systems that provide drug release in a distinct form from conventional dosage forms, either delaying or extending release. It then covers various types of modified release systems like extended release, delayed release, repeat action and targeted release. Some key technologies for achieving extended release are also summarized, like coated granules, embedding in eroding matrices, multi-tablet systems, and osmotic pumps. The seminar concludes with discussing evaluation of these systems through in vitro/in vivo correlations and dissolution studies.
Objective: The purpose of present research work is to develop the sustained release
formulation for Olmesartan medoxomil using 32
factorial design. Olmesartan an
Antihypertensive agent, angiotensin‒II receptor (type AT1) blocker and BCS class‒II
agent.
Methods: Sustained Release tablets of Olmesartan medoxomil were prepared using
different quantities of HPMCK4M and Xanthan Gum in combinations by direct
compression technique. The concentration of Polymers, HPMCK4M and Xanthan gum
required to achieve the drug release was selected as independent variables, X1 and X2
respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75%
(t75%) and 90% (t90%) were selected as dependent variables.
Results: Nine formulations were prepared and are evaluated for various
pharmacopoeial tests. The results reveals that all formulations were found to be with
in the pharmacopoeial limits and In vitro drug release profiles of all formulations were
fitted in to various Kinetic models. The statistical parameters like intercept, slope
& correlation coefficient were calculated. Polynomial equations were developed for
dependent variables. Validity of developed polynomial equations were checked by
designing 2 check point formulations (C1
, C2
).
Conclusion: According to SUPAC guidelines formulation (F5
) containing combination
of 15% HPMCK4M and 15% Xanthan gum, is the most identical formulation (similarity
factor f2
= 91.979, dissimilarity factor f1
= 1.546 & No significant difference, t=0.0338)
to marketed product (BENICAR). Best Formulation F5 follows First order, Higuchi’s
kinetics, and the mechanism of drug release was found to be Non‒Fickian Diffusion
Anomalous Transport. (n=0.828).
The document discusses novel drug delivery systems. It describes various targeted, controlled, and modulated drug delivery systems. It discusses different routes of administration including oral, pulmonary, injectable, infusion, ocular, nasal, topical, implantable, transmucosal, transdermal, and others. It also describes carrier types such as nanoparticles, liposomes, microspheres, and monoclonal antibodies. Finally, it provides details on some specific delivery methods and technologies.
This document discusses modified-release oral dosage forms, including extended-release and delayed-release forms. It describes various technologies used to modify drug release rates, such as coatings, matrices, and osmotic pumps. It also covers terminology, drug candidates suited for modified dosing, clinical considerations, and FDA/USP regulations regarding testing, labeling and in vitro-in vivo correlations. The goal of these dosage forms is to reduce dosing frequency while maintaining therapeutic drug levels over time.
The main objective of present research investigation is to formulate
the sustained release tablet of Doxofylline using 32 factorial design.
Doxofylline, an anti-Asthmatic agent, belongs BCS class-III agent.
The SR tablets of Doxofylline were prepared employing different
concentrations of HPMC K100M and Chitosan in different
combinations by Direct Compression technique using 32 factorial
design. The concentration of Polymers, HPMC K100M and
Chitosan required to achieve the desired drug release was selected as
independent variables, X1 and X2 respectively whereas, time required
for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90%
(t90%) were selected as dependent variables. Totally nine formulations
were designed, Formulated and are evaluated for hardness, friability,
thickness, % drug content, In-vitro drug release. From the Results
it was concluded that all the formulation were found to be with
in the Pharmacopoeial limits and the In-vitro dissolution profiles
of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept, slope & regression coefficient
were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were
verified by designing 2 check point formulations (C1, C2). According
to SUPAC guidelines the formulation (F4) containing combination
of 10% HPMC K100M and 15% Chitosan, is the most similar
formulation (similarity factor f2= 64.501, dissimilarity factor f1=
6.862 & No significant difference, t= 0.23001) to marketed product
(DOXOLIN). The selected formulation (F4) follows Zero order,
Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion anomalous Super Case-II Transport (n= 0.963).
Controlled release drug delivery system (cdds)articleeshweta more
The document discusses controlled release drug delivery systems (CDDS). It notes that over the last two decades, interest in these systems has remarkably increased due to factors like high drug development costs, expiration of patents, discovery of new polymers for prolonging drug release, and improved therapeutic efficiency and safety. Controlled release aims to alter a drug's pharmacokinetics and pharmacodynamics to achieve therapeutic objectives not possible with conventional dosage forms. The technology is now also applied to veterinary drugs.
Controlled Release Drug Delivery Systems - Types, Methods and ApplicationsSuraj Choudhary
This document discusses factors affecting the design of controlled release drug delivery systems (CRDDS). It outlines several key considerations for CRDDS design including selection of the drug candidate, medical and biological rationale, and physicochemical properties. It also discusses important physicochemical factors such as solubility, partition coefficient, molecular size and diffusivity, dose size, complexation, ionization constant, drug stability, and protein binding that influence CRDDS design. Finally, it briefly describes dissolution-controlled and diffusion-controlled release approaches for developing CRDDS.
Factors affecting design of Controlled Release Drug Delivery Systems (write-up)Suraj Choudhary
This document discusses factors affecting the design of controlled release drug delivery systems (CRDDS). It outlines several key considerations including selection of the drug candidate based on properties like solubility and half-life. It also discusses medical rationales like dosing frequency and patient compliance. Biological factors that influence absorption, distribution, and elimination are examined. Physicochemical properties of the drug like solubility, molecular size, and ionization must also be considered. The document provides an in-depth overview of factors involved in developing an effective CRDDS formulation.
Ms. Prajakta Sawant presented on rate controlled drug delivery systems. She discussed how these systems aim to deliver drugs at a controlled rate over an extended period of time using mechanisms like matrix diffusion and osmosis. Rate controlled systems attempt to maintain therapeutic drug levels in the body and reduce dosing frequency. Ms. Sawant classified these systems as pre-programmed, activation-modulated, feedback-regulated, or site-targeting and provided examples of each type.
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
This document discusses modified release drug delivery systems (MRDDS), including extended release, delayed release, and targeted release dosage forms. It defines MRDDS as systems that control the time and location of drug release to accomplish therapeutic objectives. The document outlines the rationale for controlled drug delivery systems (CDDS), their advantages and disadvantages, criteria for selecting drug candidates, and important physiological and biological properties to consider for CDDS.
This document discusses rate-controlled drug delivery systems. It defines sustained release and controlled release, with controlled release implying predictability and reproducibility in drug release kinetics. An ideal controlled delivery system delivers drugs at predetermined rates for specified times. Rate-preprogrammed systems release drugs at pre-set rates through polymer membranes, matrices, or microreservoirs. Activation-modulated systems activate drug release through physical, chemical, or biochemical processes. Examples of activation methods include osmotic pressure, hydrodynamic pressure, vapor pressure, and magnetism.
Formulation and Development of Matrix tablet In Drug Delivery SystemSayan Pramanik
Formulation and Development of Matrix tablet In Drug Delivery System | What is matrix tablet | merits & demerits | Classification | formulation | Evaluation |
This document discusses controlled drug delivery systems. It begins by defining controlled drug delivery systems and their goal of releasing therapeutic doses of a drug in the desired location and time period. It then discusses various types of modified release dosage forms like sustained release, extended release, and controlled release. The document covers advantages and disadvantages of these systems as well as factors influencing their design and performance. It provides examples of commercial modified release products and discusses approaches to designing controlled release formulations.
This document provides a review of matrix drug delivery systems. It begins with an introduction to oral drug delivery and the advantages of sustained release oral dosage forms over conventional immediate release forms. It then defines matrix drug delivery systems as systems that release drugs through dissolution and diffusion mechanisms, with the drug dispersed within a hydrophilic or hydrophobic polymer matrix. The rest of the document discusses the classification, advantages, disadvantages and polymers used in matrix systems. It aims to provide an in-depth overview of matrix drug delivery for sustained drug release.
1. Classical drug delivery methods like oral and injection had problems like toxicity, reduced potency, and compliance issues.
2. Controlled drug delivery aims to deploy drugs to target sites to limit side effects, maintain therapeutic levels over time, and increase compliance.
3. Early controlled delivery systems entrapped or encapsulated drugs in polymers, releasing them through diffusion or polymer erosion. Modern methods use self-assembling polymers, liposomes, nanoparticles, and antibodies to target delivery.
Development and evaluation of xyloglucan matrix release tabs contaning glipizidesukesh
The document describes a research project that developed and evaluated matrix release tablets containing the drug glipizide using xyloglucan as a polymer. Xyloglucan was extracted from tamarind kernels and used to prepare different tablet formulations. Tablets were evaluated for dissolution, drug release, and other parameters. The best formulation was F1, which released 99% of the drug in a prolonged manner and could be used for extended release of glipizide.
INTRODUCTION
Conventional oral drug delivery systems are known to provide an immediate release of drug, in which one cannot control the release of the drug and effective concentration at the target site. The bioavailability of drug from these formulations may vary significantly, depending on factors such as physico-chemical properties of the drug, presence of excipients, various physiological factors such as the presence or absence of food, pH of the GI tract, GI motility, etc. so to overcome this limitation oral route is replied by parenteral route. This route offers the advantage of reduced dose, targeting of site and avoiding GI stability, hepatic by-pass of drug molecule. (1)
In recent years, much attention has focused on novel drug delivery systems (NDDS). There are many designing options available to control or modify the drug release from a dosage form. Numerous technologies have been used to control the systemic delivery of drugs.
Based on the mechanism of the drug release can be classified as:
Diffusion controlled (matrix and reservoir type of systems)
Dissolution controlled (surface eroding, surface swelling type of systems)
Osmotic drug delivery
Multi particulate systems
Enteric coated (pH dependent systems)
One of the most interesting one is that employs osmotic pressure as an energy source for release of drugs.
The role of drug development is to take a therapeutically effective molecule with sub-optimal physicochemical and/or physiological properties and develop an optimized product that will still be therapeutically effective with additional benefits such as:
Sustained and consistent blood levels within the therapeutic window
Enhanced bioavailability
Reduced interpatient variability
Customized delivery profiles
Decreased dosing frequency
Improved patient compliance
Reduced side effects.
Osmotically controlled oral drug delivery systems (OCODDS) utilize osmotic pressure as the energy source for the controlled delivery of drugs. Drug release from these systems is independent of pH and hydrodynamic conditions of the gastro-intestinal tract (GIT) to a large extent and release characteristics can be easily adjusted by optimizing the parameters of the delivery system.
PRINCIPLE
The flow of solvent depends on SPM characteristics and different osmosis pressures between two sides of regions.
Osmosis pressure for concentrated solution of soluble solutes commonly used in controlled release formulation are extremely high, ranging from 30 atm for sodium phosphate up to 500 atm for a lactose-fructose mixture (US patent number 4077407). These osmosis pressures can produce high water flows across semi permeable membrane.
TYPES OF PUMPS
Oral Osmotic Pumps
Elementary osmotic pump(8)
Push Pull Osmotic Pump(9)
Controlled porosity Osmotic Pumps (CPOP)(10)
OROS CT System(11)
NEED OF THE STUDY
Present investigation is to develop controlled osmotic tablet of
Advances in Technologies for Formulation Development of Sterile LiquidIshani Pandit
The presentation contains the advancements in the technologies developed in the formulation of sterile liquids as well as modern devices to administer the formulation.
This document describes the formulation development and evaluation of simvastatin sustained release tablets. A 32 full factorial design was used to investigate the effect of two polymers, HPMCK4M and SCMC, on drug release times (t10%, t50%, t75%, t90%). Nine formulations were prepared according to the design and evaluated for properties like hardness, friability, thickness, drug content, and in-vitro drug release. Polynomial equations were developed relating the polymer concentrations to drug release times. The formulation containing 17.5% HPMCK4M and 30% SCMC (F4) showed drug release most similar to the marketed product and followed zero-order kinetics and non-Fickian diffusion mechanisms.
Objective: The purpose of present research work is to develop the sustained release formulation for Telmisartan using 32 factorial design. Telmisartan an Antihypertensive agent, nonpeptide angiotensin-II receptor (type AT1) antagonist and BCS class-II agent. Methods: Sustained Release tablet formulations of Telmisartan were prepared using different quantities of HPMCK100M and Xanthan Gum in combinations by direct compression technique. The concentration of Polymers, HPMCK100M and Xanthan gum required to achieve the drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. Nine formulations were prepared and are evaluated for various pharmacopoeial tests. Results: The results reveals that all formulations were found to be with in the pharmacopoeial limits and In vitro drug release profiles of all formulations were fitted in to various Kinetic models. The statistical parameters like intercept, slope & correlation coefficient were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial equations were checked by designing 2 check point formulations (C1, C2). Conclusion: According to SUPAC guidelines formulation (F5) containing combination of 15% HPMCK100M and 15% Xanthan gum, is the most identical formulation (similarity factor f2= 90.863, dissimilarity factor f1= 1.665 & No significant difference, t= 0.03379) to marketed product (TELVAS). Best Formulation F5 follows First order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion Anomalous Transport. (n= 0.828).
This seminar discusses modified release drug delivery systems. It begins with an introduction defining modified release as systems that provide drug release in a distinct form from conventional dosage forms, either delaying or extending release. It then covers various types of modified release systems like extended release, delayed release, repeat action and targeted release. Some key technologies for achieving extended release are also summarized, like coated granules, embedding in eroding matrices, multi-tablet systems, and osmotic pumps. The seminar concludes with discussing evaluation of these systems through in vitro/in vivo correlations and dissolution studies.
Objective: The purpose of present research work is to develop the sustained release
formulation for Olmesartan medoxomil using 32
factorial design. Olmesartan an
Antihypertensive agent, angiotensin‒II receptor (type AT1) blocker and BCS class‒II
agent.
Methods: Sustained Release tablets of Olmesartan medoxomil were prepared using
different quantities of HPMCK4M and Xanthan Gum in combinations by direct
compression technique. The concentration of Polymers, HPMCK4M and Xanthan gum
required to achieve the drug release was selected as independent variables, X1 and X2
respectively whereas, time required for 10% of drug release (t10%), 50% (t50%), 75%
(t75%) and 90% (t90%) were selected as dependent variables.
Results: Nine formulations were prepared and are evaluated for various
pharmacopoeial tests. The results reveals that all formulations were found to be with
in the pharmacopoeial limits and In vitro drug release profiles of all formulations were
fitted in to various Kinetic models. The statistical parameters like intercept, slope
& correlation coefficient were calculated. Polynomial equations were developed for
dependent variables. Validity of developed polynomial equations were checked by
designing 2 check point formulations (C1
, C2
).
Conclusion: According to SUPAC guidelines formulation (F5
) containing combination
of 15% HPMCK4M and 15% Xanthan gum, is the most identical formulation (similarity
factor f2
= 91.979, dissimilarity factor f1
= 1.546 & No significant difference, t=0.0338)
to marketed product (BENICAR). Best Formulation F5 follows First order, Higuchi’s
kinetics, and the mechanism of drug release was found to be Non‒Fickian Diffusion
Anomalous Transport. (n=0.828).
The document discusses novel drug delivery systems. It describes various targeted, controlled, and modulated drug delivery systems. It discusses different routes of administration including oral, pulmonary, injectable, infusion, ocular, nasal, topical, implantable, transmucosal, transdermal, and others. It also describes carrier types such as nanoparticles, liposomes, microspheres, and monoclonal antibodies. Finally, it provides details on some specific delivery methods and technologies.
This document discusses modified-release oral dosage forms, including extended-release and delayed-release forms. It describes various technologies used to modify drug release rates, such as coatings, matrices, and osmotic pumps. It also covers terminology, drug candidates suited for modified dosing, clinical considerations, and FDA/USP regulations regarding testing, labeling and in vitro-in vivo correlations. The goal of these dosage forms is to reduce dosing frequency while maintaining therapeutic drug levels over time.
The main objective of present research investigation is to formulate
the sustained release tablet of Doxofylline using 32 factorial design.
Doxofylline, an anti-Asthmatic agent, belongs BCS class-III agent.
The SR tablets of Doxofylline were prepared employing different
concentrations of HPMC K100M and Chitosan in different
combinations by Direct Compression technique using 32 factorial
design. The concentration of Polymers, HPMC K100M and
Chitosan required to achieve the desired drug release was selected as
independent variables, X1 and X2 respectively whereas, time required
for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90%
(t90%) were selected as dependent variables. Totally nine formulations
were designed, Formulated and are evaluated for hardness, friability,
thickness, % drug content, In-vitro drug release. From the Results
it was concluded that all the formulation were found to be with
in the Pharmacopoeial limits and the In-vitro dissolution profiles
of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept, slope & regression coefficient
were calculated. Polynomial equations were developed for t10%,
t50%, t75%, t90%. Validity of developed polynomial equations were
verified by designing 2 check point formulations (C1, C2). According
to SUPAC guidelines the formulation (F4) containing combination
of 10% HPMC K100M and 15% Chitosan, is the most similar
formulation (similarity factor f2= 64.501, dissimilarity factor f1=
6.862 & No significant difference, t= 0.23001) to marketed product
(DOXOLIN). The selected formulation (F4) follows Zero order,
Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion anomalous Super Case-II Transport (n= 0.963).
Controlled release drug delivery system (cdds)articleeshweta more
The document discusses controlled release drug delivery systems (CDDS). It notes that over the last two decades, interest in these systems has remarkably increased due to factors like high drug development costs, expiration of patents, discovery of new polymers for prolonging drug release, and improved therapeutic efficiency and safety. Controlled release aims to alter a drug's pharmacokinetics and pharmacodynamics to achieve therapeutic objectives not possible with conventional dosage forms. The technology is now also applied to veterinary drugs.
Controlled Release Drug Delivery Systems - Types, Methods and ApplicationsSuraj Choudhary
This document discusses factors affecting the design of controlled release drug delivery systems (CRDDS). It outlines several key considerations for CRDDS design including selection of the drug candidate, medical and biological rationale, and physicochemical properties. It also discusses important physicochemical factors such as solubility, partition coefficient, molecular size and diffusivity, dose size, complexation, ionization constant, drug stability, and protein binding that influence CRDDS design. Finally, it briefly describes dissolution-controlled and diffusion-controlled release approaches for developing CRDDS.
Factors affecting design of Controlled Release Drug Delivery Systems (write-up)Suraj Choudhary
This document discusses factors affecting the design of controlled release drug delivery systems (CRDDS). It outlines several key considerations including selection of the drug candidate based on properties like solubility and half-life. It also discusses medical rationales like dosing frequency and patient compliance. Biological factors that influence absorption, distribution, and elimination are examined. Physicochemical properties of the drug like solubility, molecular size, and ionization must also be considered. The document provides an in-depth overview of factors involved in developing an effective CRDDS formulation.
Ms. Prajakta Sawant presented on rate controlled drug delivery systems. She discussed how these systems aim to deliver drugs at a controlled rate over an extended period of time using mechanisms like matrix diffusion and osmosis. Rate controlled systems attempt to maintain therapeutic drug levels in the body and reduce dosing frequency. Ms. Sawant classified these systems as pre-programmed, activation-modulated, feedback-regulated, or site-targeting and provided examples of each type.
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
This document discusses modified release drug delivery systems (MRDDS), including extended release, delayed release, and targeted release dosage forms. It defines MRDDS as systems that control the time and location of drug release to accomplish therapeutic objectives. The document outlines the rationale for controlled drug delivery systems (CDDS), their advantages and disadvantages, criteria for selecting drug candidates, and important physiological and biological properties to consider for CDDS.
This document discusses rate-controlled drug delivery systems. It defines sustained release and controlled release, with controlled release implying predictability and reproducibility in drug release kinetics. An ideal controlled delivery system delivers drugs at predetermined rates for specified times. Rate-preprogrammed systems release drugs at pre-set rates through polymer membranes, matrices, or microreservoirs. Activation-modulated systems activate drug release through physical, chemical, or biochemical processes. Examples of activation methods include osmotic pressure, hydrodynamic pressure, vapor pressure, and magnetism.
Formulation and Development of Matrix tablet In Drug Delivery SystemSayan Pramanik
Formulation and Development of Matrix tablet In Drug Delivery System | What is matrix tablet | merits & demerits | Classification | formulation | Evaluation |
This document discusses controlled drug delivery systems. It begins by defining controlled drug delivery systems and their goal of releasing therapeutic doses of a drug in the desired location and time period. It then discusses various types of modified release dosage forms like sustained release, extended release, and controlled release. The document covers advantages and disadvantages of these systems as well as factors influencing their design and performance. It provides examples of commercial modified release products and discusses approaches to designing controlled release formulations.
This document provides a review of matrix drug delivery systems. It begins with an introduction to oral drug delivery and the advantages of sustained release oral dosage forms over conventional immediate release forms. It then defines matrix drug delivery systems as systems that release drugs through dissolution and diffusion mechanisms, with the drug dispersed within a hydrophilic or hydrophobic polymer matrix. The rest of the document discusses the classification, advantages, disadvantages and polymers used in matrix systems. It aims to provide an in-depth overview of matrix drug delivery for sustained drug release.
1. Classical drug delivery methods like oral and injection had problems like toxicity, reduced potency, and compliance issues.
2. Controlled drug delivery aims to deploy drugs to target sites to limit side effects, maintain therapeutic levels over time, and increase compliance.
3. Early controlled delivery systems entrapped or encapsulated drugs in polymers, releasing them through diffusion or polymer erosion. Modern methods use self-assembling polymers, liposomes, nanoparticles, and antibodies to target delivery.
Development and evaluation of xyloglucan matrix release tabs contaning glipizidesukesh
The document describes a research project that developed and evaluated matrix release tablets containing the drug glipizide using xyloglucan as a polymer. Xyloglucan was extracted from tamarind kernels and used to prepare different tablet formulations. Tablets were evaluated for dissolution, drug release, and other parameters. The best formulation was F1, which released 99% of the drug in a prolonged manner and could be used for extended release of glipizide.
INTRODUCTION
Conventional oral drug delivery systems are known to provide an immediate release of drug, in which one cannot control the release of the drug and effective concentration at the target site. The bioavailability of drug from these formulations may vary significantly, depending on factors such as physico-chemical properties of the drug, presence of excipients, various physiological factors such as the presence or absence of food, pH of the GI tract, GI motility, etc. so to overcome this limitation oral route is replied by parenteral route. This route offers the advantage of reduced dose, targeting of site and avoiding GI stability, hepatic by-pass of drug molecule. (1)
In recent years, much attention has focused on novel drug delivery systems (NDDS). There are many designing options available to control or modify the drug release from a dosage form. Numerous technologies have been used to control the systemic delivery of drugs.
Based on the mechanism of the drug release can be classified as:
Diffusion controlled (matrix and reservoir type of systems)
Dissolution controlled (surface eroding, surface swelling type of systems)
Osmotic drug delivery
Multi particulate systems
Enteric coated (pH dependent systems)
One of the most interesting one is that employs osmotic pressure as an energy source for release of drugs.
The role of drug development is to take a therapeutically effective molecule with sub-optimal physicochemical and/or physiological properties and develop an optimized product that will still be therapeutically effective with additional benefits such as:
Sustained and consistent blood levels within the therapeutic window
Enhanced bioavailability
Reduced interpatient variability
Customized delivery profiles
Decreased dosing frequency
Improved patient compliance
Reduced side effects.
Osmotically controlled oral drug delivery systems (OCODDS) utilize osmotic pressure as the energy source for the controlled delivery of drugs. Drug release from these systems is independent of pH and hydrodynamic conditions of the gastro-intestinal tract (GIT) to a large extent and release characteristics can be easily adjusted by optimizing the parameters of the delivery system.
PRINCIPLE
The flow of solvent depends on SPM characteristics and different osmosis pressures between two sides of regions.
Osmosis pressure for concentrated solution of soluble solutes commonly used in controlled release formulation are extremely high, ranging from 30 atm for sodium phosphate up to 500 atm for a lactose-fructose mixture (US patent number 4077407). These osmosis pressures can produce high water flows across semi permeable membrane.
TYPES OF PUMPS
Oral Osmotic Pumps
Elementary osmotic pump(8)
Push Pull Osmotic Pump(9)
Controlled porosity Osmotic Pumps (CPOP)(10)
OROS CT System(11)
NEED OF THE STUDY
Present investigation is to develop controlled osmotic tablet of
Advances in Technologies for Formulation Development of Sterile LiquidIshani Pandit
The presentation contains the advancements in the technologies developed in the formulation of sterile liquids as well as modern devices to administer the formulation.
The document summarizes the development of an extended release formulation of bupropion hydrochloride tablets. The objectives were to develop a stable, cost-effective ER formulation and compare it to marketed products. Various ER tablet formulations were prepared using different concentrations of coating polymers and evaluated for drug release. Formulations F9 and F10, which used 8% coating of ethylcellulose 15cps, showed comparable release to the reference product over 16 hours. The developed formulation met the objectives of providing a once-daily ER tablet for bupropion hydrochloride.
The document discusses various techniques for scaling up capsule production in a pilot plant setting. It describes the basic manufacturing process for hard and soft gelatin capsules. For hard capsules, this involves mixing ingredients, granulation, capsule making, filling, and packaging. Soft capsules involve formulating liquid or semi-solid fills and using various manufacturing methods like plate, rotary die press, or bubble processes to encapsulate the fills. Key considerations for scale-up include powder flow properties and lubricant distribution for hard capsule filling.
Pilot plant scale up techniques for solid dosage formsElahehEntezarmahdi
This document discusses techniques for scaling up solid dosage form production from pilot plants. It covers key steps like material handling, blending, granulation, drying, particle size reduction, slugging, compression, coating and capsule filling. For each step, parameters important for process control are identified, such as equipment type, material properties, loading amounts, time, temperature and humidity settings. The goal of scaling up is to control these parameters to consistently produce quality products at larger volumes.
Formulation and evaluation of sustained release tablets of ambroxol hcl using...Venkatesh Pillala
This document provides an introduction and literature review for formulating and evaluating sustained release tablets of Ambroxol HCl using natural polymers. It discusses sustained release dosage forms, factors affecting oral sustained release dosage forms, parameters for drug selection, formulation methods, and mechanisms of drug release from matrix tablets. The literature review covers previous studies on formulating sustained release dosage forms for other drugs using natural polymers. The objective is stated as preparing and evaluating sustained release tablets of Ambroxol HCl to improve its oral bioavailability, reduce dosing frequency, and optimize polymer concentrations.
This document provides an overview of fundamentals of modified release formulations. It discusses different mechanisms for controlling drug release including diffusion controlled, dissolution controlled, and erosion controlled systems. It describes key aspects of reservoir and matrix devices for diffusion controlled release as well as encapsulation and matrix systems for dissolution controlled release. The document also covers erosion controlled delivery, hybrid systems, relevant mathematical models, and some examples of marketed modified release products.
The role of dissolution in the demonstration of bioequivalenceinemet
PharmaCon2007 Congress, Dubrovnik, Croatia "New Technologies and Trends in Pharmacy, Pharmaceutical Industry and Education" http://www.pharmacon2007.com
Abstract is available at http://www.pharmaconnectme.com
Accelerated Stability During Formulation Development of Early Stage Protein T...KBI Biopharma
2008 IBC Formulation Strategies for Protein Therapeutics, Accelerated Stability During Formulation Development of Early Stage Protein Therapeutics – Pros and Cons of Contrasting Approaches. Vice President, Biopharmaceutical Development
Tim Kelly, Ph.D. KBI Biopharma, Inc.
Formulation development of insoluble drugs has always been a challenge in pharmaceutical development. This presentation reviews some current options to old problem.
Scale up and post approval changes(supac)bdvfgbdhg
The document discusses guidelines for post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and composition. It outlines 3 levels of changes - minor, moderate, and major - and provides recommendations for documentation and regulatory filings required for each level of change. Major changes, such as a new manufacturing site or changes in the amount of active ingredients, require more extensive documentation including stability testing and possibly bioequivalence studies.
Oral sustained and controlled release dosage forms Dr Gajanan Sanap
This document discusses oral sustained and controlled release dosage forms. It begins with an introduction and overview of rationality in designing sustained release drug formulations. It defines sustained release as formulations that continuously release medication over an extended period after a single dose to achieve prolonged therapeutic effects. Controlled release aims to deliver drug at a predetermined rate for a specified time period to maintain constant drug levels. The document outlines the differences between controlled and sustained release. It discusses objectives and advantages of sustained release formulations as well as challenges and factors to consider in design.
This document provides an overview of aerosols for pharmaceutical use. It begins with introductions to aerosols and pharmaceutical aerosols. The main components of aerosols are then described, including propellants, containers, valves, and actuators. Various aerosol systems like solution, suspension, and foam systems are also outlined. The document concludes with sections on the formulation, manufacturing, and quality control of pharmaceutical aerosols.
This document describes various types of dosage forms including their definitions, classifications, and examples. It discusses oral dosage forms like tablets, capsules, liquids, and others. It also covers topical forms like ointments, creams, gels and more. Rectal forms like suppositories and enemas are outlined. Vaginal forms such as pessaries and rings are defined. Finally, it briefly discusses parenteral forms including intravenous and intramuscular injections. The document provides detailed information on the characteristics and uses of different dosage forms for drug delivery.
This document discusses oral drug delivery systems, specifically oral controlled release systems and gastroretentive drug delivery systems. It defines continuous and pulsatile release oral controlled release systems. Matrix systems and reservoir systems are described as the two main types of continuous release systems. Gastroretentive drug delivery systems are designed to prolong gastric residence time to allow for sustained drug release in the stomach. Approaches for prolonging gastric retention time include high density, floating, swelling/expanding, and mucoadhesive systems. Specific technologies like osmotic pumps, hollow microspheres, and alginate beads are also summarized.
This document discusses pharmaceutical technology and considerations for developing drug dosage forms. Pharmaceutical technology deals with formulating new chemical entities into safe and effective medications for patients. Medicines contain drug substances formulated with excipients into dosage forms for delivery. Different dosage forms serve various purposes like protecting drugs, masking tastes, providing liquids or controlled release. Major considerations in designing dosage forms include physicochemical properties, biochemistry, and determining the optimal product type based on development goals. Therapeutic factors are also assessed like treatment type and patient attributes to select the appropriate dosage form.
ABSTRACT
Objective: The main objective of present investigation is to formulate the controlled release tablet of Lamivudine using 3² factorial design. Lamivudine, a basic molecule and antiretroviral drug belongs to BCS Class III, having low permeability and high solubility. Methods: The controlled release tablets of lamivudine were prepared employing different concentrations of Carboplol974P and Xanthan gum in different combinations as a rate retarding agent by Direct Compression technique using 32 factorial design. The quantity/ concentration of rate retarders, Carboplol974P and Xanthan gum required to achieve the desired drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution t10%, t50%, t75%,t90% were selected as dependent variables. Results: Totally nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, in-vitro drug release. From the results it was concluded that all the formulation were found to be with in the pharmacopoeial limits and the in-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for t10%, t50%, t75%,t90%. Conclusions: According to SUPAC guidelines the formulation (F5) containing combination of 10% Carboplol974P and 10% Xanthan gum, is the most similar formulation (similarity factor f2=85.04 & No significant difference, t= 0.20046) to Innovator product (Lamivir). The selected formulation (F5) follows Higuchi’s kinetics, and the mechanism of drug release was found to be Case-II transport or typical Zero order release (Non-Fickian, n= 0.915).
This document describes the design and evaluation of atenolol gastroretentive floating tablets using a 3^2 factorial design. Nine formulations were prepared using different concentrations of HPMC K15M and sodium bicarbonate as independent variables. The dependent variables measured were the time taken for 10%, 50%, 75%, and 90% drug dissolution. Formulation F8, containing 25% HPMC K15M and 3.75% sodium bicarbonate, showed prolonged drug release similar to the marketed product and followed Higuchi kinetics with non-Fickian diffusion-controlled drug release. Polynomial equations were developed relating the independent and dependent variables.
Objective: The purpose of the present research investigation was to formulate sustained release (SR) formulations for
losartan potassium using 32
factorial designs. Methods: Losartan potassium is an antihypertensive agent, non-peptide
angiotensin-II receptor (type AT1) blocker, and BCS class-III agent. SR tablet formulations of losartan potassium were
formulated using variable quantities of hydroxymethyl propyl cellulose (HPMC) K100M and xanthan gum in combinations
by direct compression technique. The amount of polymers, HPMC K100M, and xanthan gum required to achieve the drug
release was selected as independent variables, X1
and X2
, respectively, whereas time required to release 10% (t10%), 50%
(t50%), 75% (t75%), and 90% (t90%) of drug from formulation was selected as dependent variables. Nine formulations were
prepared and evaluated for various pharmacopoeial tests. Results: The results reveal that all formulations were found to be
with in the pharmacopoeial limits and in vitro drug release profiles of all formulations were subjected to kinetic modeling.
The statistical parameters such as intercept, slope, and correlation coefficient were determined. Polynomial equations were
developed for dependent variables. Validity of developed polynomial equations was checked by designing two checkpoint
formulations (C1
and C2
). According to SUPAC guidelines, formulation (F4
) containing mixture of 15% HPMC K100M
and 20% xanthan gum is the most identical formulation (similarity factor f2 = 86.747, dissimilarity factor f1 = 1.760, and no
significant difference, t = 0.0477) to marketed product (LOSACAR). Conclusion: Best Formulation F4 follows the first-order,
Higuchi kinetics, and the mechanism of drug release was found to be non-Fickian diffusion anomalous transport (n = 0.825).
KEY WORDS: 32 factorial design, First-order kinetics, Hydroxymethyl propyl cellulose K100M, Losartan potassium,
Non-fickian diffusion mechanism, Sustained release tablet, Xanthan gum
Formulation and Evaluation of Enalapril Maleate SR Matrix TabletsBhaswat Chakraborty
1. The study developed and evaluated sustained release matrix tablets of enalapril maleate using HPMC KM and HPMC K15 M polymers by wet granulation.
2. In vitro drug release studies showed that formulations F9 and F10 best matched the target release profile, releasing drug over 5 hours.
3. Kinetic modeling showed that drug release from the HPMC matrices followed Higuchi kinetics, indicating that the release mechanism involved both diffusion and erosion of the polymer matrices.
Formulation and Evaluation of Stavudine Controlled Release Matrix TabletSunil Vadithya
The document presents a study on the formulation and evaluation of controlled release matrix tablets of Stavudine. Stavudine was selected as a model drug due to its short half-life. Hydroxypropyl methylcellulose (HPMC) and Carbopol 934 were used as release retarding polymers to develop sustained release matrix tablets. Tablets were prepared by direct compression method and evaluated for physical parameters, drug content, swelling index and in-vitro drug release up to 8 hours. The results showed that formulations containing higher proportions of polymers released the drug in a controlled manner for an extended period of time.
The main objective of the present research work is to formulate the Clopidogrel Fast Dissolving tablets. Clopidogrel, an antiplatelet drug, belongs to BCS Class-II and used to control Heart attack, Hypertension by inhibiting Platelet activation and aggregation .The Fast Dissolving tablets of Clopidogrel were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrant by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50%, t90% were selected as dependent variables. Totally nine formulations were designed and evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, and in-vitro drug release. From the Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the in-vitro dissolution profiles of all formulations were fitted into different Kinetic models, the statistical parameters like intercept (a), slope (b) and regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations was verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines, the formulation (F5) containing combination of 15% Crospovidone and 15% Croscarmellose, is the most similar formulation (similarity factor f2=91.3936, dissimilarity factor f1= 1.203& No significant difference, t= -0.00062) to marketed product (PLAVIX-75). The selected formulation (F1) follows First order, Higuchi’s kinetics, mechanism of drug release found to be Fickian Diffusion (n= 0.226).
This document discusses advances in monitoring pharmacotherapeutics and drug delivery system design. It begins with definitions of pharmacotherapy and the need for monitoring it to ensure safe and effective use of drugs. It then discusses factors like adverse drug reactions, rational drug use, and improving patient compliance. Recent advances in monitoring discussed include microscopy techniques for examining drug fate and distribution in tissues. The document also discusses trends in pharmaceutical product design like controlled release and targeted delivery systems. Specific advances highlighted include prodrug approaches, nanocarrier systems, and delivery methods like Ocusert inserts and buccal patches.
The document provides an overview of oral controlled release drug delivery systems. It discusses the anatomy and physiology related to oral drug administration. Some key advantages of controlled release oral dosage forms are enhanced bioavailability, reduced dosing frequency, and more consistent drug levels in the body. The document also covers various mechanisms for controlled release, including osmotic pumps, floating systems, and coating technologies. It provides examples of commercially available controlled release drugs and classifications of these systems.
The main aim of present research study is to formulate the floating tablets of Labetalol HCl using 32 factorial design. Labetalol HCl, non selective α, -β- adreno receptor antagonist, Indicated for treatment of Hypertension/moderate Heart Failure. The Floating tablets of Labetalol HCl were prepared employing different concentrations of HPMCK4M and sodium bicarbonate in different combinations by Direct Compression technique. The concentration of HPMCK4M and sodium bicarbonate required to achieve desired drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables. 9 formulations were designed and are evaluated for hardness, friability, thickness, % drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all the formulation were found to be within the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept, slope & regression coefficient were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations. According to SUPAC guidelines the formulation (F8) containing combination of 20% HPMCK4M and 3.75% sodium bicarbonate, is the most identical formulation which meets the objective of work. The selected formulation (F8) follows Higuchi’s kinetics, and the mechanism of drug release was found to be NonFickian Diffusion (n= 1.033, Super Case-II transport).
ABSTRACT The purpose of this study was to prepare and evaluate immediate release itraconazole pellets and comprehensive studies of the same. The itraconazole pellets is prepared using fluid bed processer with different concentration of HPMC (Hydroxy Propyl Methyl Cellulose). The physicochemical compatibility of the drug and the excipient studied by differential scanning calorimetry. The prepared pellets were physically evaluated with size, shape, bulk density, tapped density, compressibility index, hausners ratio, angle of repose, sieve analysis, surface roughness, density, moisture content, assay and drug release etc. The in vitro drug release profile from pellets shows that all the formulation release more than 75% drug within 90min. Optimized formulations were found to have HPMC concentration 2-5% of total weight of pellets to maximize high-quality surface, desired release, and size distribution within the range. These results indicate that pellets containing 10 % HPMC of total weight of pellets give better quality of itraconazole pellets for immediate release. Key Words: Itraconazole, Hydroxyl propyl methyl cellulose and Immediate release.
Background: The main objective of present research work is to formulate the Carbamazepine Fast Dissoving tablets. Carbamazepine, an
antiepileptic, belongs to BCS Class-II and used to control some types of seizures in the treatment of epilepsy and Neuropathic Pain by
blocking use-dependent sodium channels. Methods: The Fast Dissoving tablets of Carbamazepine were prepared employing different
concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Sperdisintegrants by Direct Compression technique
using 32
factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1
and X2 respectively whereas, wetting time, Disintegration time, t
50% ,t90%were selected as dependent variables. Results and Discussion:
Totally nine formulations were designed and are evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, Invitro
drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) &
regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations (C1
, C2
). According to SUPAC guidelines the
formulation (F5
) containing combination of 9.375% Crospovidone and 9.375% Croscarmellose, is the most similar formulation (similarity factor
f
2
=82.675, dissimilarity factor f1
= 2.049 & No significant difference, t= 0.041) to marketed product (TEGRETOL-100). Conclusion: The
selected formulation (F5
) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.665).
KEYWORDS: Carbamazepine, 3
2Factorial Design, Crospovidone , croscarmellose Sodium, Wetting Time, Disintegration Time.
Formulation and evaluation of lamivudine controlled release tabletsSriramNagarajan17
This document summarizes the formulation and evaluation of controlled release tablets containing the drug Lamivudine. Lamivudine tablets were prepared using different polymers like Xanthum, Guar gum, HPMC, and CMC to achieve controlled release. The tablets were evaluated for various physicochemical properties. In vitro drug release studies showed that all formulations released up to 97% of the drug over 24 hours. Formulation F5 was selected as the optimized formulation based on evaluation results and in vitro drug release profile. Kinetic studies indicated that the drug release from the optimized formulation followed zero-order kinetics.
Relation between biopharmaceutics and Dosage form design MdJahangirAlam110
This 6-page document discusses the relationship between biopharmaceutics and dosage form design. It begins by defining biopharmaceutics as the study of factors that influence the rate and amount of drug reaching systemic circulation in order to optimize drug efficacy. These factors include drug product design, stability, manufacture, release from the product, dissolution rate, and delivery to the site of action. It then discusses key concepts like absorption, distribution, elimination, and metabolism that influence this relationship. The document explains how solubility, permeability, stability, and pharmacokinetics impact drug bioavailability and effectiveness. It also notes how intended use, patient acceptability, and safety must be considered in dosage form design. In general, liquid dosage forms are more readily
This document discusses prodrug design. It defines prodrugs as pharmacologically inert derivatives that can be converted in vivo to the active drug molecule. The goals of prodrug design are to overcome undesirable drug properties related to absorption, distribution, metabolism and toxicity. Examples are given of prodrugs that increase oral absorption or provide targeted delivery to tumors. Prodrugs are evaluated based on their physicochemical properties and pharmacokinetic profile to ensure they are converted to the active drug molecule.
This document describes the formulation and evaluation of an osmotic drug delivery system for propranolol hydrochloride. Six formulations of an osmotic tablet were developed using different osmogens. The tablets were evaluated for physical properties and in vitro drug release. Formulations using mannitol as the osmogen showed controlled release for 12 hours, making it the optimized formulation. Osmotic drug delivery systems offer advantages like controlled release over an extended period, but require evaluation of factors like osmogen concentration to achieve the desired release profile.
Formulation development and evalution of matrix tablet ofGajanan Ingole
The document describes the development of a matrix tablet for oral delivery of an antihypertensive drug (NSL) using pH dependent and independent polymers. It includes sections on introduction, literature review, drug and excipient profiles, aim and objectives, rationale, materials and equipment, experimental work, results, discussion, and references. The key steps involved preformulation studies, formulation of matrix tablets, optimization studies to match the in vitro dissolution profile of a marketed reference product, and stability studies. The optimized formulation was found to release the drug in a controlled manner for 24 hours.
This document discusses the importance of preformulation studies in designing sustained release dosage forms. Preformulation studies provide important information about the drug substance including solubility, pH effects, partitioning, stability and compatibility with excipients. This information guides the selection of appropriate formulation components, manufacturing processes and container closure systems. Key preformulation tests described include determining intrinsic solubility, dissociation constant (pKa), partition coefficient, crystal properties, and dissolution rate. The results of preformulation studies help develop stable, bioavailable sustained release dosage forms that can be mass produced.
This document discusses the importance of preformulation studies in designing sustained release dosage forms. Preformulation studies provide important information about the drug substance that can be used to develop stable and bioavailable sustained release formulations. Key aspects of preformulation include determining solubility, pKa, partition coefficient, crystal properties, and compatibility with excipients. This information helps select appropriate formulation components, manufacturing processes, container closure systems and more. The overall goal of preformulation is to generate data to support the development of sustained release dosage forms that can be mass produced and provide a prolonged therapeutic effect.
Similar to Formulation Development and Evaluation of Rosiglitazone Maleate Sustained Release Tablets using 32 Factorial Design (20)
Objective: The purpose of the current research work was to study effect of formulation variables in a statistical way for the SR formulations of Valsartan sodium. Methods: Valsartan sodium is an antihypertensive agent angiotensin‒II receptor blocker belongs to BCS class‒III agent. SR tablet formulations of Valsartan sodium were formulated using variable quantities of HPMCK100M and Xanthan Gum by direct compression method. quantities of polymers was chosen as independent variables, X1 and X2 respectively whereas, time required for dissolution 10%(t10%), 50%(t50%), 75%(t75%) and 90%(t90%) of drug from formulation were chosen as dependent variables. 9 formulations were prepared and evaluated for various pharmacopoeial tests. Results: The results reveals that all formulations were found to be with in the acceptable limits and release rate profiles of all formulations were fitted to kinetic models. The statistical parameters were determined. Polynomial equations were developed for dependent variables. Validity of them was checked by countercheck formulations (C1 ,C2 ). According to SUPAC guidelines, formulation (F4) containing mixture of 12% HPMCK100M and 16% Xanthan gum, was found to be identical formulation (dissimilarity factor f1 =1.763, similarity factor f2 =86.747 & No significant difference, t=0.0478) to marketed product (VALZAAR). Conclusion: Formulation F4 follows First order kinetics, Non‒Fickian Diffusion Anomalous Transport. (n=0.826).
The main objective was to formulate fast dissolving tablets of Amisulpride using a 32 full factorial design to study the effects of different concentrations of crospovidone and croscarmellose sodium on tablet properties. Nine formulations were prepared using combinations of 9%, 7%, or 5% crospovidone and 9%, 7%, or 5% croscarmellose sodium. Tablet properties like disintegration time, wetting time, and drug release at 50% and 90% were evaluated. Formulation F1 containing 9% of each superdisintegrant showed the fastest disintegration and drug release, most similar to the marketed product. Polynomial equations were derived relating the superdisintegrant concentrations to the response variables.
ABSTRACT
Objective: Stroke is one of the leading causes of death and disabilities worldwide. Cost-effectiveness analysis helps identify neglected opportunities
by highlighting interventions that are relatively inexpensive, yet have the potential to reduce the disease burden substantially. In India, there are
wide social and economic disparities. Socioeconomic environment influences occupation, lifestyle, and nutrition of social classes which in turn would
influence the prevalence and profile of stroke. By reduction of delays in access to hospital and improving provision of affordable treatments can
reduce morbidity and mortality in patients with stroke in India. This study is designed to measure and compare the costs (resources consumed) and
consequences (clinical, economic, and humanistic) of pharmaceutical products and services and their impact on individuals, healthcare systems and
society.
Methods: The purpose of this study is to analyze and conduct a cost-effectiveness analysis for the treatment of stroke in Guntur City Hospitals.
The patients were treated either with aspirin or clopidogrel. The health outcomes were measured using Modified Rankin Scale, A prominent risk
assessment scale for stroke. The pharmacoeconomic data were computed from the patient data collection forms.
Result: The incremental cost-effectiveness ratio of aspirin and clopidogrel were calculated to be Rs. 8046.2/year.
Conclusion: The study concludes that aspirin has the increased socioeconomic impact when compared to Clopidogrel and we can see that the earlier
therapy has supported discharge, home-based rehabilitation along with reduced hospital stay and hence preferable.
Keywords: Stroke, Pharmacoeconomics, Cost-effectiveness analysis, Aspirin, Clopidogrel, Incremental cost-effectiveness ratio.
In recent years many advancement has been made in research and development of Oral Drug Delivery System. Concept of Novel Drug Delivery System arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations.
Purpose of this review is to compile the recent literature with special focus on Gastro Retentive Drug Delivery Systems to give an update
on pharmaceutical approaches used in enhancing the Gastric Residence Time (GRT). Various approaches are currently used including Gastro Retentive Floating Drug Delivery Systems(GRFDDS),swelling and expanding system, polymeric bioadhesive systems, modifiedshape
systems, high density system and other delayed gastric emptying devices. These systems are very helpful to different problem solve during the formulation of different dosage form. The present work also focuses on the polymers used in floating drug delivery systems
mostly from natural origin. Floating drug delivery systems are less dense than gastric fluids; hence remain buoyant in the upper GIT for a
prolonged period, releasing the drug at the desired/ predeterminedrate. This review article focuses on the recent technological development in floating drug delivery systems with special emphasis on the principal mechanism of floatation and advantages of achieving gastric
retention, brief collection on various polymers employed for floating drug delivery systems etc. In addition this review also summarizes the In –Vitro and In -Vivo studies to evaluate their performance and also their future potential.
This document discusses the rational use of drugs and the issues with irrational drug use. It begins by discussing how antibiotics were initially hailed as miracle drugs that saved many lives, but bacteria eventually evolved resistance. It then defines rational drug use as prescribing the correct drug, dose, and duration based on a patient's needs. Some reasons for irrational drug use include a lack of information, training, diagnostic facilities, and effective regulation. The hazards of irrational drug use include ineffective treatment, prolonged illness, increased costs, and harm to patients. It emphasizes only using antibiotics with proper dosing and duration, avoiding self-medication, and educating others. In conclusion, it states that medicines must be used properly to be effective and avoid harm.
The document discusses antidepressants in chronic pain relief. It provides background on chronic pain and classifies pain based on pathophysiology, duration, etiology, and anatomy. It then discusses the pathophysiology of nociceptive and neuropathic pain in detail. The document reviews various types of antidepressants and their mechanisms of action. It summarizes evidence from multiple studies that tricyclic antidepressants and selective serotonin reuptake inhibitors can effectively treat chronic pain conditions like diabetic neuropathy and post-herpetic neuralgia at doses lower than those used for depression. The antidepressants may relieve pain through mechanisms other than their antidepressant effects.
Background: The main aim of present research investigation is to formulate the Risperidone Fast Dissolving tablets. Risperidone, an atypical antipsychotic, belongs to BCS Class-II and used for treating schizophrenia, bipolar mania and autism by blocking D2 and 5-HT2A receptors. Methods: The Fast Dissolving tablets of Risperidone were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrants by Direct Compression technique using 32 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X1 and X2 respectively whereas, wetting time, Disintegration time, t50% ,t90%were selected as dependent variables. Results and Discussion:
Totally nine formulations were designed, preapred and are evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, In-vitro drug release. From the Results concluded that all the formulation were found to be with in the Pharmacopoeial limits and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t50%, t90%. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F5) containing combination of 10% Crospovidone and 10% Croscarmellose, is the most similar formulation (similarity factor f2= 93.556, dissimilarity factor f1= 0.976& No significant difference, t= 0.022) to marketed product (RISPERDAL-4). Conclusion: The selected formulation (F5) follows First order, Higuchi’s kinetics, mechanism of drug release was found to be Fickian Diffusion (n= 0.383).
ABSTRACT
Background:The main objective of the study is to determine the anti-arthritic effect of whole plant ethanolic extract of Polygonum glabrum
belonging to the family Polygonaceae in Female wistar rats using the Freund’s Complete Adjuvant (FCA) model . Methods:The plants areal
parts were collected near Tirupathi hills, Chittoor district of Andhra Pradesh in India. The Phytoconstituents were identified through the
chemical tests. Ethanol (95%) was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for antiarthritic
screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of P.glabrum was studied at doses
of 250 and500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, theliver enzyme levels were
determined and a radiological examination was carried out. Results and Discussion:The preliminary phytochemical analysis of the ethanolic
extract of Polygonum glabrum showed the presence of alkaloids, tannins, flavonoids and saponins. P. glabrum at 250 and 500 mg/kg
significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control
animals exhibited a significant decrease in body weight compared with control animals without arthritis. P. glabrum treated animals showed
dose dependent reduction in decrease in body weight and arthritis.At the same time, P.glabrum significantly altered the biochemical and
haematological changes induced by FCA (P < 0.05). The anti-arthritic effect of P.glabrum was comparable with that of Indomethacin.
Conclusion:The whole plant extract of P.glabrum showed significant anti-arthritic activity against FCA-induced arthritis in female Wistar
rats.
ABSTRACT
Over the last decade, diabetes mellitus has emerged as an important clinical and public health
problem throughout the world. The aim of the study is perceive the Potentiality of a newer oral
Antihyperglycemic combination therapy over conventional therapy in type 2 diabetes. The
prospective study was conducted over a period of six months in the department of Medicine,
Guntur City Hospital. The prevalence of type2 diabetes was high in male 65.79 % than female
34.21%. Majority of the patients (23.68 %) belonged to age group of 51–55 years. Majority of
patients (55.26%) having a family history of Diabetes. Majority of patients receiving Combination
of Glibenclamide + Metformin (60.53%), evaluated for effect on FPG for both combinations. The
mean changes in FPG were noted. In the same way effect on HbA1c also noted. Mean changes in
for every month HbA1c will be noted. Our study reveals that Combination therapy with Metformin
plus Glimepiride is more effective than Glibenclamide plus Metformin; in improving glycemic
control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.
Aim of the study: The objective of present study is to report a rare Case of contact dermatitis that was seen in 30 years old female from Narasaraopet of Guntur district, South India. Place of study: This case was studied in the outpatient department of Dermatology, Guntur City Hospital, Guntur. Period of Study: This case was studied and investigated in detail in the month of May 2014 in the above hospital. Case Report: A young female aged 30years came with past history of Hyperthyroidism for the past 11months and Obese. She needed support to have food. On examination she had Hoarse throat, Body pains Irregular periods .along with this on application of Raw Garlic for pimples turned into Contact Dermatitis. This study was compared and well correlated with available literature. Conclusion: Since this is a rare case of Garlic Induced Hypersensitivity reaction made us interesting to study.
This study evaluated the anti-inflammatory properties of the aqueous extract of Solena amplexicaulis leaves in rats. Rats were injected with egg white to induce paw edema and treated with the extract, diclofenac sodium (standard drug), or saline (control). Paw volume was measured over 60 minutes. The extract significantly reduced paw edema compared to control, demonstrating anti-inflammatory effects comparable to diclofenac sodium. The extract likely inhibits the release of inflammatory mediators like histamine and prostaglandins. Therefore, the aqueous extract of S. amplexicaulis leaves has potent anti-inflammatory activity.
The document discusses rectal drug delivery systems. It provides a brief history of rectal medications dating back to ancient civilizations. It describes the anatomy and physiology of the human rectum, noting its length, pH, blood supply, and limited surface area available for drug absorption. Several advantages and disadvantages of the rectal route are outlined. Factors affecting drug absorption from the rectum include physiological factors of the drug and rectum as well as physicochemical properties of the drug. Common rectal dosage forms include creams, ointments, suppositories, solutions, and suspensions. The document discusses these forms in detail and provides examples of commercial rectal products.
The document discusses osmotic drug delivery systems, which use osmotic pressure to control drug release. It describes the principles of osmosis, advantages and disadvantages of osmotic systems, components of osmotic pumps like semipermeable membranes and osmogens, and various types of osmotic pumps. The document provides details on the design and working of osmotic pumps for controlled drug delivery.
This document discusses ocular drug delivery systems. It begins by noting the importance of the eye and challenges in delivering drugs to it. Topical eye drops and ointments are commonly used but much of the drug is quickly drained away. Novel delivery systems aim to increase drug absorption and targeting to the front and back segments of the eye. These include microemulsions, nanosuspensions, nanoparticles, and liposomes, which can help prolong drug residence time and enhance permeability. The document also reviews challenges in ocular delivery and strategies to improve bioavailability such as viscosity enhancers, gels, prodrugs, and bioadhesive polymers.
This document discusses nasal drug delivery systems. It covers advantages like avoidance of first-pass metabolism and rapid drug absorption. Disadvantages include potential nasal irritation and smaller absorption surface area compared to the GI tract. Factors influencing nasal absorption are drug properties, pH, and permeability enhancers. Common formulations use drugs, viscosity agents, solubilizers, and preservatives. Nasal delivery can be used for non-peptide drugs, peptides, and diagnostics by exploiting the nasal mucosa for absorption.
The document discusses buccal drug delivery using the buccal mucosa. It notes that the buccal mucosa lines the inner cheek and can be used to treat both local and systemic conditions. It then discusses the advantages of buccal delivery in avoiding first-pass metabolism and providing a less hostile environment than the GI tract. Various buccal dosage forms are described including tablets, patches, films and gels. Key factors influencing drug delivery via this route like drug properties and type of dosage form are also summarized.
This document discusses bioadhesive drug delivery systems. It begins by defining bioadhesion as the interfacial molecular forces that allow polymers to adhere to biological surfaces for extended periods of time. It then discusses various bioadhesive polymers, both natural and synthetic, that are commonly used in drug delivery formulations. These include polymers like acacia gum, alginic acid, carbomers, and hyaluronic acid. The document also outlines the three main mechanisms by which bioadhesion occurs: wetting and swelling of polymers, interpenetration of polymer chains with mucosal membranes, and formation of chemical bonds between entangled chains. Finally, it provides examples of different types of bioadhesive drug delivery formulations that can
The document discusses various topics related to tablet compression including compression, consolidation, compaction, energy involved, tablet strength parameters like crushing strength and friability, and issues like lamination. It provides details on the energy expended during different stages of compression and how lubricants can reduce this. Tablet strength is found to increase with compression force and binder concentration but decrease with porosity. Tests for evaluating tablet properties like hardness, friability and lamination tendency are also summarized.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
हिंदी वर्णमाला पीपीटी, hindi alphabet PPT presentation, hindi varnamala PPT, Hindi Varnamala pdf, हिंदी स्वर, हिंदी व्यंजन, sikhiye hindi varnmala, dr. mulla adam ali, hindi language and literature, hindi alphabet with drawing, hindi alphabet pdf, hindi varnamala for childrens, hindi language, hindi varnamala practice for kids, https://www.drmullaadamali.com
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Formulation Development and Evaluation of Rosiglitazone Maleate Sustained Release Tablets using 32 Factorial Design
1. International Journal of PharmTech Research
CODEN (USA): IJPRIF, ISSN: 0974-4304
Vol.8, No.4, pp 713-724, 2015
Formulation Development and Evaluation of Rosiglitazone
Maleate Sustained Release Tablets using 32
Factorial Design
Raghavendra Kumar Gunda
Department of Pharmaceutics, Narasaraopeta Institute of Pharmaceutical Sciences,
Narasaraopet, Guntur (Dt), Andhra Pradesh, India-522601
Abstract: The main objective of present investigation is to formulate the sustained release
tablet of Rosiglitazone Maleate using 32
factorial design. Rosiglitazone Maleate, an oral anti-
diabetic agent. The SR tablets of Rosiglitazone Maleate were prepared employing different
concentrations of HPMCK15M and Carboplol934P in different combinations as a rate
retardants by Direct Compression technique using 32
factorial design. The quantity/
concentration of Polymers , HPMCK15M and Carboplol934P required to achieve the desired
drug release was selected as independent variables, X1 and X2 respectively whereas, time
required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were
selected as dependent variables. Totally nine formulations were designed and are evaluated
for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it
was concluded that all the formulation were found to be with in the Pharmacopoeial limits
and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic
models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r)
were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 25%
HPMCK15M and 20% Carboplol934P, is the most similar formulation (similarity factor
f2=93.1376, dissimilarity factor f1= 1.7642 & No significant difference, t= 0.06949) to
marketed product (AVANDIA). The selected formulation (F5) follows Higuchi’s kinetics,
and the mechanism of drug release was found to be Fickian Diffusion (n= 0.417).
Keywords: Rosiglitazone Maleate, 32
Factorial Design, Sustained Release Tablet,
HPMCK15M , Carbopol934P, SUPAC, Fickian Diffusion Mechanism, Zero order kinetics.
Introduction
Oral administration is the most convenient, widely used route for both conventional and novel drug
delivery systems, and preferred route of drug delivery for systemic action. Tablets are the most popular oral
solid formulations available in the market and are preferred by patients and physicians alike. There are many
reasons for this, not the least of which would include acceptance by the patient and ease of administration . In
long-term therapy for the treatment of chronic disease conditions, conventional formulations are required to be
administered in multiple doses and therefore have several disadvantages1
. However, when administered orally,
many therapeutic agents are subjected to extensive presystemic elimination by gastrointestinal degradation
and/or first pass hepatic metabolism as a result of which low systemic bioavailability and shorter duration of
therapeutic activity and formation of inactive or toxic metabolites2
.
Sustained release (SR) tablet formulations are preferred for such therapy because they offer better
patient compliance, maintain uniform drug levels, reduce dose and side effects, and increase the safety margin
for high-potency drugs1
.
2. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 714
Over the past 30 years, as the expense and complications involved in marketing new drug entities have
increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, the goal in
the designing sustained / controlled drug delivery system is to reduce the dosing frequency or to increase
effectiveness of the drug by localization at the site of action, reducing the dose required, or providing uniform
drug delivery3
.
Sustained release dosage forms may be defined as any drug or dosage form modification that prolonged
but not necessarily uniform release of drug. The goal of a sustained release dosage form is to maintain
therapeutic blood or tissue levels of the drug for an extended period. This is usually accomplished by attempting
to obtain zero-order release from the dosage form. Zero-order release constitutes the drug release from the
dosage form that is independent of the amount of drug in the delivery system (i. e., constant release rate).
Sustained release systems generally do not attain this type of release and usually try to mimic zero-order release
by providing drug in a slow first-order fashion (i. e., concentration dependent). Systems that are designated as
prolonged release can also be considered as attempts at achieving sustained release delivery4,5
.
Sustained release tablet allowing a 2 fold or greater reduction in frequency of administration of a drug
in comparison with the frequency required by a Prompt release dosage form6,7
. Sustained release products
provide advantage over Immediate release dosage form by optimising biopharmaceutical, pharmacokinetic and
pharmacodynamic properties of drug. Sustained release dosage forms have been demonstrated to improve
therapeutic efficiency by maintenance of a steady drug plasma concentration8,9
.
Oral controlled drug delivery system represents one of the frontier areas of drug delivery system in
order to fulfill the need for a long-term treatment with anti-HIV agents, anti-Diabetics(Oral
Hypoglycaemics))10
. Among the different controlled drug delivery (CDD) systems, matrix based controlled
release tablet formulations are the most popularly preferred for its convenience to formulate a cost effective
manufacturing technology in commercial scale. Development of oral controlled release matrix tablets
containing water-soluble drug has always been a challenging because of dose dumping due to improper
formulation resulting in plasma fluctuation and accumulation of toxic concentration of drug(Peak-Valley
Concentration)11
. The use of polymers in controlling the release of drugs has become an important tool in the
formulation of pharmaceutical dosage forms. Over many years, numerous studies have been reported in the
literature on the application of hydrophilic polymers in the development of controlled release matrix systems
for various drugs 12,13,14
.
Since the early 1950s, the application of polymeric materials for medical purposes is growing very fast.
Polymers have been used in the medical field for a large extent 15
. Natural polymers remain attractive primarily
because they are inexpensive, readily available, be capable of chemical modifications, non-carcinogenicity,
mucoadhesivity, biodegradable, biocompatible, high drug holding capacity and high thermal stability and easy
of compression 16
. This led to its application as excipient in hydrophilic drug delivery system. The various
natural gums and mucilages have been examined as polymers for sustained drug release in the last few decades
for example; guar gum, tragacanth gum, xanthan gum, pectin, alginates etc. In the development of a sustained
release tablet dosage form. Availability of wide variety of polymer and frequent dosing interval helps the
scientist to develop sustained release product. cellulose derivatives such as carboxymethyl cellulose (CMC),
sodium carboxymethyl cellulose, hydroxyproyl cellulose (HPC), and hydroxypropyl methyl cellulose (HPMC)
have been extensively studied as polymer in the controlled release tablet formulations17
. These polymers are
most preferred because of its cost effectiveness, broad regulatory acceptance, non-toxic and easy of
compression. These dosage forms are available in extended release, targeted release, delayed release, prolonged
action dosage form. Some factors like molecular size, diffusivity, pKa-ionization constant, release rate, dose
and stability, duration of action, absorption window, therapeutic index, protein binding, and metabolism affect
the design of sustained release formulation. The future of sustained release products is promising in some area
like chronopharmacokinetic system, targeted drug delivery system, mucoadhesive system, particulate system
that provide high promise and acceptability.
Developing oral-sustained release formulations for highly water-soluble drugs with constant rate of
release has become a challenge to the pharmaceutical technologists. Fast release drug generally causes toxicity
if not formulated as extended release dosage form. Among various formulation approaches, in controlling the
release of water-soluble drugs, the development of sustained release coated granules has a unique advantage of
lessening the chance of dose dumping which is a major problem when highly water-soluble drug is formulated
as matrix tablets. Most of the researchers have worked on matrix tablets and multilayered matrix tablets.
Among numerous approaches to oral SR formulation, matrix system of dosage form proves to be potential
3. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 715
because of its simplicity, ease of manufacturing, low cost, high level of reproducibility, stability, ease of scale
up, and process validation 18
.
Oral sustained release dosage form by direct compression technique is a simple approach of drug
delivery systems that proved to be rational in the pharmaceutical arena for its ease, compliance, faster
production, avoid hydrolytic or oxidative reactions occurred during processing of dosage forms19
.
The selection of the drug candidates for sustained release system needs consideration of several
biopharmaceutical, pharmacokinetic and pharmacodynamic properties of drug molecule20
.
In the present study, a sustained release dosage form of Rosiglitazone Maleate has been developed that
makes less frequent administering of drug.
Rosiglitazone is an antidiabetic agent belongs to the class of Thiazolidinediones, used in management
of type-two diabetes mellitus. Rosiglitazone maleate has a half life of (3‐4hr) and it reaches a peak plasma
concentration after 1hrs and which is absorbed from gastrointestinal tract but solubility decreases with
increasing pH in the physiologic range21,22
. After 8 to 12 weeks of Rosiglitazone monotherapy, the dose may be
doubled in case of insufficient response and this leads to higher incidence of dose dependent side effects. Such
as gastro-intestinal disturbances, headache, altered blood lipids, oedema, hypoglycaemia. Further, adverse
events of clinical significance which are reported frequently with conventional instant release dosage forms of
the drug are oedema, anaemia and weight gain . Thus, there is a need to maintain Rosiglitazone at its steady
state plasma concentration. Hence, the study was carried out to formulate and evaluate sustained release dosage
form of Rosiglitazone Maleate as a model drug and had a aim that final batch formulation parameters should
shows prolong drug release.
Development of dosage form depends on chemical nature of the drug/polymers, matrix structure,
swelling, diffusion, erosion, release mechanism and the in vivo environment.
It is an important issue is to design an optimized formulation with an appropriate dissolution rate in a
short time period and minimum trials. Many statistical experimental designs have been recognized as useful
techniques to optimize the process variables. For this purpose, response surface methodology (RSM) utilizing a
polynomial equation has been widely used. Different types of RSM designs include 3-level factorial design,
central composite design (CCD), Box-Behnken design and D-optimal design. Response surface methodology
(RSM) is used when only a few significant factors are involved in experimental optimization. The technique
requires less experimentation and time, thus proving to be far more effective and cost-effective than the
conventional methods of formulating sustained release dosage forms23,24,25,26
.
Hence an attempt is made in this research work to formulate Sustained release (SR) Tablets of
Rosiglitazone Maleate using HPMCK15M andCarbopol934P . Instead of normal and trial method, a standard
statistical tool design of experiments is employed to study the effect of formulation variables on the release
properties.
Large scale production needs more simplicity in the formulation with economic and cheapest dosage
form. The SR tablets formulation by direct compression method is most acceptable in large scale production.
A 32
full factorial design was employed to systematically study the drug release profile . A 32
full
factorial design was employed to investigate the effect of two independent variables (factors), i.e the amounts of
HPMCK15M and Carbopol 934P on the dependent variables, i.e. t10%, t50%, t75%, t90%, ( Time taken to release
10%,50%75%,90% respectively)
Materials and Methods
Materials used in this study were obtained from the different sources. Rosiglitazone Maleate was a gift
sample from Aurobindo pharma Ltd, Hyderabad, India. HPMCK15M, Carbopol934P, Di Calcium Phosphate
and Micro Crystalline Cellulose were procured from Loba Chemie Pvt.Ltd, Mumbai. Other excipients such as
Aerosil and magnesium stearate were procured from S.D. Fine Chem. Ltd., Mumbai.
4. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 716
Formulation Development of Rosiglitazone Maleate Sustained Release Tablets:
The factorial design is a technique that allows identification of factors involved in a process and
assesses their relative importance. In addition, any interaction between factors chosen can be identified.
Construction of a factorial design involves the selection of parameters and the choice of responses27
.
A selected three level, two factor experimental design (32
factorial design) describe the proportion in
which the independent variables HPMCK15M and Carbopol934P were used in formulation of Rosiglitazone
Maleate sustained release (SR) Tablets. The time required for 10% (t10%), 50% (t50%), 75% (t75%) and 90% (t90%)
drug dissolution were selected as dependent variables. Significance terms were chosen at 95% confidence
interval (p<0.05) for Final Equations. Polynomial equations were developed for t10%, t50%, t75%, t90%, (step-wise
backward Linear Regression Analysis).
The three levels of factor X1 (HPMCK15M) at a concentration of 20%, 25%, 30%. three levels of
factor X2 (Carbopol934P) at a concentration of 15%, 20%, 25%.(% with respect to total tablet weight) was
taken as the rationale for the design of the Rosiglitazone Maleate SR tablet formulation. Totally nine
Rosiglitazone Maleate sustained release tablet formulations were prepared employing selected combinations of
the two factors i.e X1, X2 as per 32
Factorial and evaluated to find out the significance of combined effects of
X1, X2 to select the best combination and the concentration required to achieve the desired prolonged/ sustained
release of drug from the dosage form.
Preparation of Rosiglitazone Maleate Sustained Release Tablets:
All ingredients were collected and weighed accurately. Sift Rosiglitazone Maleate with
Microcrystalline Celulose and polymers through sieve no. 44# and then rinse with remaining excipients. Sift
colloidal silicon dioxide (Aerosil-200) and magnesium stearate separately, through sieve no. 60#. Pre-blend all
ingredients (except lubricant- magnesium stearate) in blender for 15 minutes. Add magnesium stearate and then
again blend for 5-6 minutes. Lubricated powder was compressed by using rotary tablet punching machine
(RIMEK), Ahmedabad). Compressed tablets were examined as per official standards and unofficial tests.
Tablets were packaged in well closed light resistance and moisture proof containers.
Experimental Design:
Experimental design utilized in present investigation for the optimization of polymer concentration
such as, concentration of HPMCK15M was taken as X1 and concentration of Carbopol934P was taken as X2.
Experimental design was given in the Table 1. Three levels for the Concentration of HPMCK15M were
selected and coded as -1= 20%, 0=25%, +1=30%. Three levels for the Concentration of Carbopol934P were
selected and coded as -1= 15%, 0=20%, +1=25%. Formulae for all the experimental batches were given in
Table 2 28,29
.
Table 1: Experimental Design Layout
Formulation Code X1 X2
F1 1 1
F2 1 0
F3 1 -1
F4 0 1
F5 0 0
F6 0 -1
F7 -1 1
F8 -1 0
F9 -1 -1
5. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 717
Table 2: Formulae for the Preparation of Rosiglitazone Maleate Sustained Release Tablets as per
Experimental Design
Name of Ingredients
Quantity of Ingredients per each Tablet (mg)
F1 F2 F3 F4 F5 F6 F7 F8 F9
Rosiglitazone Maleate 16 16 16 16 16 16 16 16 16
Microcrystalline Cellulose 30 30 30 30 30 30 30 30 30
HPMCK15M 120 120 120 100 100 100 80 80 80
Carbopol934P 100 80 60 100 80 60 100 80 60
Di Calcium Phosphate 127 147 167 147 167 187 167 187 207
Aerosil 2 2 2 2 2 2 2 2 2
Magnesium Stearate 5 5 5 5 5 5 5 5 5
Total Weight 400 400 400 400 400 400 400 400 400
Evaluation of Rosiglitazone Maleate Sustained Release Tablets:
Hardness29
The hardness of the tablets was tested by diametric compression using a Monsanto Hardness Tester. A
tablet hardness of about 2-4 kg/cm2
is considered adequate for mechanical stability.
Friability21
The friability of the tablets was measured in a Roche friabilator (Camp-bell Electronics, Mumbai).
Tablets of a known weight (W0) or a sample of 20 tablets are dedusted in a drum for a fixed time (100
revolutions) and weighed (W) again. Percentage friability was calculated from the loss in weight as given in
equation as below. The weight loss should not be more than 1 %
Friability (%) = [(Initial weight- Final weight) / (Initial weight)] x 100
Content Uniformity29
In this test, 20 tablets were randomly selected and the percent drug content was determined, the tablets
contained not less than 85% or more than 115% of the labelled drug content can be considered as the test was
passed.
Assay22
The drug content in each formulation was determined by triturating 20 tablets and powder equivalent to
average weight was added in 100ml of 0.1N Hydrochloric acid, followed by stirring. The solution was filtered
through a 0.45μ membrane filter, diluted suitably and the absorbance of resultant solution was measured
spectrophotometrically at 318nm using 0.1 N Hydrochloric acid as blank.
Thickness 29
Thickness of the all tablet formulations were measured using vernier calipers by placing tablet between
two arms of the vernier calipers.
In-vitro Dissolution Study:
The In-vitro dissolution study for the Rosiglitazone Maleate sustained release tablets were carried out
in USP XXIII type-II dissolution test apparatus (Paddle type) using 900 ml of 0.1 N HCl as dissolution medium
at 50 rpm and temperature 37±0.5°C. At predetermined time intervals, 5 ml of the samples were withdrawn by
means of a syringe fitted with a pre-filter, the volume withdrawn at each interval was replaced with same
quantity of fresh dissolution medium. The resultant samples were analyzed for the presence of the drug release
by measuring the absorbance at 318 nm using UV Visible spectrophotometer after suitable dilutions. The
determinations were performed in triplicate (n=3).
Kinetic modeling of drug release:
The dissolution profile of all the formulations was fitted in to zero-order, first-order, Higuchi and
Korsmeyer-peppas models to ascertain the kinetic modeling of drug release30,31,32,33
.
6. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 718
Results and Discussion:
Sustained release tablets of Rosiglitazone Maleate were prepared and optimized by 32
factorial design in
order to select the best combination of different rate retarding agents, HPMCK15M, Carbopol934P and also to
achieve the desired prolong/sustained release of drug from the dosage form. The two factorial parameters
involved in the development of formulations are, quantity of HPMCK15M & Carbopol934P polymers as
independent variables (X1, X2), and In vitro dissolution parameters such as t10%, t50% , t75% & t90% as dependent
variables. Totally nine formulations were prepared using 3 levels of 2 factors and all the formulations
containing 16 mg of Rosiglitazone Maleate were prepared as a sustained release tablet dosage form by Direct
Compression technique as per the formulae given in Table 2.
All the prepared tablets were evaluated for different post compression parameters, drug content, mean
hardness, friability, mean thickness, mean diameter as per official methods and results are given in Table 3. The
hardness of tablets was in the range of 5.17-5.50 Kg/cm2
. Weight loss in the friability test was less than 0.67%.
Drug content of prepared tablets was within acceptance range only. Results for all Post-compression
parameters were tabulated or shown in Table 3. In-vitro Dissolution studies were performed for prepared tables
using 0.1 N HCl as a dissolution media at 50 rpm and temperature 37±0.5°C. The In-vitro dissolution profiles
of tablets are shown in Fig.1 and the dissolution parameters are given in Table 4. Cumulative % Drug release of
Factorial Design Formulations F1-F9 at 12Hr were found to be in the range of 80.010-90.500 %. From the result
it reveals that the release rate was higher for formulations containing Low level of HPMCK 15M/
Carbopol934P compared with other Formulations containing Higher level, due to High concentration of
polymer drug may have entrapped within a polymer matrix causing a decrease in rate of drug release.
Therefore, required release of drug can be obtained by manipulating the composition of HPMCK15M and
Carbopol934P.
Table 3: Post-Compression Parameters for the Formulations
S.
No
Formulation
Code
Hardness
(kg/cm2
)
Diameter
(mm)
Thickness
(mm)
Friability
(%)
Weight
Variation
Drug
Content
(%)1 F1 5.30 13.66 6.30 0.212 400.97 98.32
2 F2 5.28 13.62 6.29 0.215 400.80 98.23
3 F3 5.17 13.53 6.22 0 .217 399.93 97.88
4 F4 5.20 12.98 6.16 0.225 400.067 97.44
5 F5 5.37 12.90 6.12 0.667 400.617 97.36
6 F6 5.40 12.87 6.10 0.258 400.217 97.00
7 F7 5.50 11.47 5.80 0.175 400.817 96.40
8 F8 5.40 12.86 6.08 0.208 400.45 96.65
9 F9 5.50 12.20 5.93 0.080 400.033 96.04
Table 4: Regression Analysis Data of 32
Factorial Design Formulations of Rosiglitazone Maleate
F1 to F9 are factorial formulations, r-correlation coefficient, a-Intercept, b-Slope and MP-Marketed Product.
S.
No
Form
ulati
on
Code
Kinetic Parameters
Zero Order First Order Higuchi Korsmeyer-Peppas
a b r a b r a b r a b r
1 F1 7.446 7.795 0.986 2.106 0.064 0.977 24.47 28.353 0.928 0.126 1.774 0.990
2 F2 6.682 7.790 0.987 2.105 0.065 0.978 23.82 28.390 0.931 0.259 1.636 0.993
3 F3 5.465 7.967 0.987 2.109 0.070 0.978 23.34 29.189 0.936 0.396 1.510 0.994
4 F4 5.182 8.057 0.988 2.111 0.073 0.979 23.43 29.598 0.939 0.375 1.549 0.991
5 F5 4.390 8.127 0.988 2.112 0.075 0.980 23.06 29.972 0.943 0.417 1.517 0.989
6 F6 3.226 8.184 0.989 2.118 0.080 0.979 22.17 30.246 0.946 0.548 1.384 0.991
7 F7 3.250 8.197 0.987 2.113 0.079 0.981 22.36 30.353 0.946 0.510 1.428 0.989
8 F8 2.219 8.256 0.989 2.122 0.083 0.979 21.58 30.622 0.950 0.601 1.339 0.991
9 F9 1.419 8.452 0.988 2.133 0.091 0.979 21.54 31.484 0.953 0.626 1.332 0.988
10 MP 3.762 8.155 0.988 2.113 0.077 0.980 22.63 30.133 0.945 0.474 1.461 0.990
7. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 719
Much variation was observed in the t10% , t50%, t75% and t90% due to formulation variables. Formulation F5
containing 100 mg of HPMCK15M, 80 mg of Carbopol934P showed promising dissolution parameter (t10%=
0.609 h, t50% = 4.007 h, t75% = 8.014 h, t90% = 13.315 h). The difference in burst effect of the initial time is a result
of the difference in the viscosity of the polymeric mixtures. Dortunc and Gunal have reported that increased
viscosity resulted in a corresponding decrease in the drug release, which might be due to the result of thicker gel
layer formulation34
.
Fig.1 Comparative Zero Order Plots for F1-F9 Fig.2 Comparative First Order Plots for F1-F9
Fig.3 Comparative Higuchi Plots for F1-F9 Fig.4 Comparative Korsmeyer-Peppas Plots for F1-F9
The In -vitro dissolution data of Rosiglitazone Maleate SR formulations was subjected to goodness of
fit test by linear regression analysis according to zero order and first order kinetic equations, Higuchi’s and
Korsmeyer-Peppas models to assess the mechanism of drug release. The results of linear regression analysis
including regression coefficients are summarized in Table 4 and plots shown in fig.1,2,3,4. It was observed
from the above that dissolution of all the tablets followed zero order kinetics with co-efficient of determination
(R2
) values above 0.986. The values of r of factorial formulations for Higuchi’s equation was found to be in the
range of 0.928-0.953, which shows that the data fitted well to Higuchi’s square root of time equation
confirming the release followed diffusion mechanism. Kinetic data also treated for Peppas equation, the slope
(n) values ranges from 0.126- 0.626 that shows Fickian diffusion mechanism. Polynomial equations were
derived for t10%, t50%, t75% and t90% values by backward stepwise linear regression analysis. The dissolution data
(Kinetic parameters) of factorial formulations F1 to F9 are shown in Table 5.
8. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 720
Table 5: Dissolution Parameters of Rosiglitazone Maleate Sustained Release Tablets 3² Full Factorial
Design Batches
Polynomial equation for 3² full factorial designs is given in Equation
Y= b0+b1 X1+b2 X2+b12 X1X2+b11 X1²+b22 X2²…
Where, Y is dependent variable, b0 arithmetic mean response of nine batches, and b1 estimated co-
efficient for factor X1. The main effects (X1 and X2) represent the average result of changing one factor at a
time from its low to high value. The interaction term (X1X2) shows how the response changes when two factors
are simultaneously changed. The polynomial terms (X1² and X2²) are included to investigate non-linearity.
Validity of derived equations was verified by preparing Two Check point Formulations of Intermediate
concentration(C1, C2).
The equations for t10%, t50% t75% and t90% developed as follows,
Y1= 0.612+0.072X1+0.0325X2-0.005X1X2+0.01067 X1
2
-0.01084X2
2
(for t10%)
Y2= 4.026+0.471X1+0.214X2-0.029 X1X2+0.0696 X1
2
-0.0688 X2
2
(for t50%)
Y3= 8.053+0.943X1+0.429X2-0.058 X1X2+0.140 X1
2
-0.138 X2
2
(for t75%)
Y4 = 13.380+1.567X1+0.712X2-0.097 X1X2+0.232 X1
2
-0.229 X2
2
(for t90%)
Table 6: Dissolution Parameters for Predicted and Observed Values for Check Point Formulations
Formulation
Code
Predicted Value Actual Observed Value
t10% (h) t50% (h) t75% (h)) t90% (h) t10% (h) t50% (h) t75% (h)) t90% (h)
C1 0.53 3.50 6.99 11.05 0.54 3.49 7.01 11.06
C2 0.69 4.52 9.04 15.04 0.69 4.53 9.06 15.05
The positive sign for co-efficient of X1 in Y1, Y2, Y3 and Y4 equations indicates that, as the
concentration of HPMCK15M increases, t10%, t50%, t75% and t90% value increases. In other words the data
demonstrate that both X1 (amount of HPMCK15M) and X2 (amount of Carbopol934P) affect the time required
for drug release (t10%, t50%, t75% and t90%). From the results it can be concluded that, and increase in the amount of
the polymer leads to decrease in release rate of the drug and drug release pattern may be changed by appropriate
selection of the X1 and X2 levels. The Dissolution parameters for predicted from the polynomial equations
derived and those actual observed from experimental results are summarised in Table 6. The closeness of
Predicted and Observed values for t10%, t50%, t75% and t90% indicates validity of derived equations for dependent
variables. The Contour Plots were presented to show the effects of X1 and X2 on t10%, t50%, t75% and t90%. The final
best (Optimised) formulation (F5) is compared with marketed product (AVANDIA)shows similarity factor (f2)
93.1376, difference factor (f1) 1.7642 (There is no significant difference in drug release because tcal is<0.05).
S.No
Formulation
Code
Kinetic Parameters
t10% (h) t50% (h) t75% (h)) t90% (h)
1 F1 0.711 4.680 9.360 15.552
2 F2 0.700 4.606 9.212 15.306
3 F3 0.650 4.277 8.554 14.212
4 F4 0.630 4.148 8.295 13.783
5 F5 0.609 4.007 8.014 13.315
6 F6 0.575 3.785 7.569 12.576
7 F7 0.581 3.825 7.650 12.711
8 F8 0.548 3.604 7.208 11.975
9 F9 0.502 3.306 6.611 10.985
10 MP 0.594 3.906 7.813 12.981
9. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 721
Fig.5 linear Contour Plot for t10% Fig.6 Contour Plot for t10%
Fig.7 linear Contour Plot for t50% Fig.8 Contour Plot for t50%
Fig.9 linear Contour Plot for t75% Fig.10 Contour Plot for t75%
10. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 722
Fig.11 linear Contour Plot for t90% Fig.12 Contour Plot for t90%
Conclusion
The present research work envisages the applicability of rate retarding agents such as HPMCK15M and
Carbopol934P in the design and development of sustained release tablet formulations of Rosiglitazone Maleate
utilizing the 32
factorial design. From the results it was clearly understand that as the retardant concentration
increases the release rate of drug was retarded and both of these polymers can be used in combination since do
not interact with the drug which may be more helpful in achieving the desired sustained release of the drug for
longer periods. The optimized formulation followed Higuchi’s kinetics while the drug release mechanism was
found to be Fickian Diffusion, Zero order release type, controlled by diffusion through the swollen matrix. On
the basis of evaluation parameters, the optimized formulation F5 may be used once a day administration in the
management of Type-II Diabetes mellitus.
Acknowledgements:
The author would like to thank Management, Principal, Teaching, Non-teaching Staff of Narasaraopeta
Institute of Pharmaceutical Sciences, Narasaraopet, Guntur (D.t), A.P., India for providing support for
successful completion of research work.
References
1. Swati Jain, Neelesh Kumar Mehra, Akhlesh Kumar Singhai and Gaurav Kant Saraogi. Development
and evaluation of sustained release matrix tablet of lamivudine. IJPSR, 2011; Vol. 2(1): 454-461
2. R. Ruben Singh. Design, Formulation And In Vitro Evaluation Of Lamivudine Hcl Sustained Release
Tablets. International Journal of Research in Pharmaceutical and Nano Sciences, 2014; 3(2): 113 – 121.
3. Y. Ganesh kumar, j. Sreekanth, d. Satyavati. Formulation development and in vitro evaluation of
sustained release matrix tablets of bosentan by using synthetic polymers. Int J Pharm Pharm Sci,2014;
6( 11): 111-118
4. Bankar GS, Rhodes CT. Eds. Modern Pharmaceutics. 3
rd
edn. Marcel Dekker, Inc. New York; 1996. p.
668-9.
5. Lachmann L, Lieberman HA, Kanig JL. The Theory & Practice of Industrial Pharmacy. Varghese
Publishing House, Bombay, 3rd Edition; 1991. p. 430.
6. VNL. Sirisha*, Y. Kiran Kumarrao and M. Chinna Eswaraiah. Formulation and Evaluation of
Lamivudine and Zidovudine Extended Release Tablets. International Journal of Research in
Pharmaceutical and Biomedical Sciences, 2012; 3 (4): 1759-1763.
7. John C and Morten C. The Science ofDosage Form Design, Aulton: Modified release peroral dosage
forms, (2nded) Churchill Livingstone. 2002:290-300.
11. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 723
8. Turner S, Federici C, Hite M, Fassihi R. Formulation development and human in vitro - in vivo
correlation for a novel, monolithic controlled- release matrix system of high load and highly water
soluble drug Niacin, Drug Dev Ind Pharm, 30(8), 2004, 797-807.
9. Fernandes CM, Ramos P, Amilcar CF, Veiga FB. Hydrophilic and hydrophobic cyclodextrins in a new
sustained release oral formulation of Nicardipine: In vitro evaluation and bioavailability studies in
rabbits, J. Control.Release, 88(1), 2003, 127-134.
10. Atul K, Ashok KT, Narendra KJ, Subheet J. Formulation and in vitro, in vivo evaluation of extended-
release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix
formers. AAPS Pharm Sci Tech 2006;7 Suppl 1:E1-E9.
11. Al-saidan SM, Krishnaiah YSR, Patro S, Satyaranayana V. In vitro and in vivo evaluation of guar gum
matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. AAPS Pharm Sci
Tech 2005;6 Suppl 1:E14-E21.
12. Ravi PR, Ganga S, Saha RN. Design and study of lamivudine oral controlled release tablets. AAPS
Pharm Sci Tech 2007;8 Suppl 4:167-75.
13. Badshah A, Subhan F, Shah NH, Bukhari NI, Saeed M Shah KU. Once daily controlled release matrix
tablet of prochlorperazine maleate: Influence of Ethocel® and/or Methocel® on in vitro drug release
and bioavailability. Drug Dev Ind Pharm 2012;38 Suppl 2:190-9.
14. Singh B, Rani A, Babita, Ahuja N, Kapil R. Formulation optimization of hydrodynamically balanced
oral controlled release bioadhesive tablets of tramadol hydrochloride. Sci Pharm 2010;78 Suppl 2:303-
23..
.
15. Ravi PR, Ganga S, Saha RN. Design and study of lamivudine oral controlled release tablets. J
American Association of Pharm Scientists Pharm Sci Tech 2007;8 (4):1-9.
16. Prakash P, Porwal M, Saxena A. Role of natural polymers in sustained release drug delivery
system:application and recent approaches. Int Res J of Pharmacy 2011;2(9):6-11.
17. Nelson kenneth, varadarajan parthasarathy, chikkanna narendra, prakasam kalyani. Development and
evaluation of oral controlled release matrix tablets of lamivudine optimization and in vitro-in vivo
studies . Int j pharm pharm sci 2015: 7 (1):95-101
18. Abdul S.Althaf, Design and Study of Lamivudine Oral Sustained Release Tablets, Der Pharmacia
Sinica, 2010;1(2): 61-76.
19. Amidon, GL and R Löbenberg. Modern Bioavailability, Bioequivalence and Biopharmaceutics
Classification system. New Scientific Approaches to International Regulatory Standards. Eur. J.
Pharm. Biopharm 2000; 50: 3–12.
20. Rhodes C.T., Robinson J.R., Sustained and controlled drug delivery system; In Banker GS, editor,
Modern Pharmaceutics, 4th ed., USA:Marcel Dekker.2003; pp 503-505.
21. Dhankhar Neelam, Kumar Sunil, Goyal Surinder, Ramana Jaspreet, Mishra Sushmita. Formulation and
In-Vitro Evaluation of Gastro Retentive Rosiglitazone Maleate Floating Tablet.International Journal of
Research in Pharmacy and Science. 2011:1(2):57-66.
22. Kavitha K, Puneeth K P, Tamizh mani T. Development and evaluation of Rosiglitazone Maleate
Floating Tablets. International journal of applied pharmaceutics, 2010;2(2):6-10.
23. M.A.Shende, R.P.Marathe, S.B. Khetmalas, P. N. Dhabale. Studies on development of Sustained
release Diltiazem hydrochloride matrices through jackfruit mucilage. International journal of pharmacy
and pharmaceutical sciences, 2014; 6, (7): 72-78.
24. Swarbrick J, Boylan JC. Optimization techniques in formulation and processing, Encyclopedia of
Pharmaceutical technology. New York:Marcel Dekker;1994. p. 70.
25. Montgomery DC. Introduction to factorial deigns. Design and Analysis of Experiments. 5th ed. Wiley
India Pvt. Ltd:New Delhi;2004. p. 170-217.
26. Schwartz BJ, Connor RE. Optimization technique in pharmaceutical formulations and processing. J
Drugs and Pharm Sci in Modern Pharmaceutics 1996;72(3):727-54.
27. A. A. Kharia, s. N. Hiremath, a. K. Singhai, l. K. Omray and s. K. Jain. Design and Optimization of
Floating Drug Delivery System of Acyclovir, Indian J. Pharm. Sci., 2010, 72 (5): 599-606.
28. Ramesh C. Nagarwal. In Situ Forming Formulation: Development, Evaluation, and Optimization Using
33
Factorial Design, AAPS PharmSciTech, 2009; Vol. 10, No. 3, 977-984.
29. Raghavendra Kumar Gunda, J. N. Suresh Kumar, Ch Ajay Babu and M. V. Anjaneyulu. Formulation
Development and Evaluation of Lamotrigine Sustained Release Tablets Using 32
Factorial Design,
IJPSR, 2015; Vol. 6(4): 1746-1752.
12. Raghavendra Kumar Gunda /Int.J. PharmTech Res. 2015,8(4),pp 713-724. 724
30. K.P.R.chowdary, optimization of valsartan tablet formulation by 23
factorial design, JGTPS, 2014;
Volume 5, Issue 1,1374-1379 .
31. Notari RE. Biopharmaceutics and clinical pharmacokinetics. 4th ed. New York: Marcel Dekker Inc;
1987. p. 6-21.
32. Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid
drugs dispersed in solid matrices. J Pharm Sci 1963; 51:1145-9.
33. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv 1985;
60:110-1.
34. Dortunc B, Gunal N. Release of acetazolamide from swellable HPMC matrix tablets. Drug Dev Ind
Pharm 1997; 23:1245-9.
*****