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.
Introduction to Nasal drug delivery system,Anatomy of Nasal cavity,Advantages n limitataions of Nasal DDS,Mechanism,factors affecting Nasal DDS,Formulation,methods to enhance Nasal DDS,Dosage forms,Evalaution
Introduction to Nasal drug delivery system,Anatomy of Nasal cavity,Advantages n limitataions of Nasal DDS,Mechanism,factors affecting Nasal DDS,Formulation,methods to enhance Nasal DDS,Dosage forms,Evalaution
It consists the details about the pharmaceutical formulations and development as well as new drug development.
It consists the different stages in clinical trials.
It have the details about new drug application process
ANDA
NDA
FDA APPROVAL
IND APPLICATION
CLINICAL TRIALS AND RESEARCH
New drug invention
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
This PPT includes a brief introduction of in silico models for simulation of GI absorption of drugs, principles involved in the dvelopment of computational models for in silico pharmacokinetic studies related to absorption of drugs from GI tract.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
ABSTRACT
Overactive bladder (OAB) is a prevalent condition which has an adverse effect on quality of life. The presence
of urgency incontinence confers significant morbidity above and beyond that of OAB sufferers who are
continent. The primary treatment for OAB and urgency incontinence is a combination of behavioral measures
and antimuscarinic drug therapy. The ideal antimuscarinic agent should effectively relieve the symptoms of
OAB, with the minimum of side effects; it should be available as a once-daily sustained release formulation
and in dosage strength that allows easy dose titration for the majority of sufferers. Solifenacin succinate was
launched in 2005 and has been shown in both short and long term clinical trials to fulfill these requirements.
Solifenacin is a competitive M3 receptor antagonist with a long half-life (45-68 hours). It is available in two
dosage strengths namely a 5 or 10 mg once-daily tablet. The efficacy and tolerability of solifenacin for the
treatment of all symptoms of OAB has been evaluated in a number of large, placebo controlled, randomized
trials. Long-term safety, efficacy, tolerability and persistence with treatment have been established in an open
label 40 week continuation study.
KEYWORDS
Solifenacin, Urinary incontinence, Overactive bladder and Wet granulation method.
It consists the details about the pharmaceutical formulations and development as well as new drug development.
It consists the different stages in clinical trials.
It have the details about new drug application process
ANDA
NDA
FDA APPROVAL
IND APPLICATION
CLINICAL TRIALS AND RESEARCH
New drug invention
Gastrointestinal absorption simulation using in silico methodology; by Dr. Bh...bhupenkalita7
This PPT includes a brief introduction of in silico models for simulation of GI absorption of drugs, principles involved in the dvelopment of computational models for in silico pharmacokinetic studies related to absorption of drugs from GI tract.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
This PPT includes what role does Dosage form impart on absorption. Why it is important in absorption. what should be its nature and type of dosage form.
ABSTRACT
Overactive bladder (OAB) is a prevalent condition which has an adverse effect on quality of life. The presence
of urgency incontinence confers significant morbidity above and beyond that of OAB sufferers who are
continent. The primary treatment for OAB and urgency incontinence is a combination of behavioral measures
and antimuscarinic drug therapy. The ideal antimuscarinic agent should effectively relieve the symptoms of
OAB, with the minimum of side effects; it should be available as a once-daily sustained release formulation
and in dosage strength that allows easy dose titration for the majority of sufferers. Solifenacin succinate was
launched in 2005 and has been shown in both short and long term clinical trials to fulfill these requirements.
Solifenacin is a competitive M3 receptor antagonist with a long half-life (45-68 hours). It is available in two
dosage strengths namely a 5 or 10 mg once-daily tablet. The efficacy and tolerability of solifenacin for the
treatment of all symptoms of OAB has been evaluated in a number of large, placebo controlled, randomized
trials. Long-term safety, efficacy, tolerability and persistence with treatment have been established in an open
label 40 week continuation study.
KEYWORDS
Solifenacin, Urinary incontinence, Overactive bladder and Wet granulation method.
Design expert software assisted development and evaluation of cefpodoxime pro...Makrani Shaharukh
Cefpodoxime Proxetil is third generation, broad-spectrum Cephalosporin Antibiotic & it has an oral bioavailability of only 50% and biological half life 2 h so to improve it’s bioavailability sustain release matrix formulation was designed. Sustained release matrix tablets of Cefpodoxime Proxetil prepared by direct compression method based on combination of natural Acacia gum & Karaya gum polymers. 32 full factorial designs optimization study was carried out by using Design Expert Software to find the effect of independent variables, i.e., Acacia gum (X1) and Karaya gum (X2) concentration on dependent variables i.e., Hardness & % CDR. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, in-vitro drug release, kinetic studies and stability studies. FTIR and DSC studies shown there was no interaction between drug and polymers. Matrix tablet of Cefpodoxime Proxetil were formulated well in term of hardness 5.07 ± 0. 5.93 ± 0.03 kg/cm2, thickness 2.25 ± 0.1 mm to 3.33 ± 0.3 mm, weight variation were within limits. In-vitro release studies show that almost 90 % of drug was release from all the formulation were within 12 h. Formulation F5 selected as a optimized one since it showed optimum hardness & sustained drug release within 12 h in comparison to other formulation. The F5 optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. 32 full factorial design optimization technique was successfully used in this research work. Developed matrix tablets of Cefpodoxime Proxetil produced a sustained and effective drug release over a prolonged time frame that led to greater therapeutic efficacy.
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).
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.
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).
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 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).
ABSTRACT
Hyperglycemia is the technical term for high blood glucose (sugar). It
happens when the body has too little or not enough insulin or when the
body can‘t use insulin properly. The main objective of the present
research work was to develop a bilayer tablet of immediate release
Pioglitazone and controlled release Metformin Hydrochloride, which is
used as an Anti-hyperglycemic agent. Metformin Hydrochloride has
biological half-life nearly about 6 hours, so, an attempt was made in
the direction of preparation and optimization of a combination of
sustained release and immediate release in a single tablet. In controlled
release layer natural gums like xanthum gum, gum trgacanth and guar
gum were used as retarding materials and in immediate release laye
croscarmellose sodium was used as a superdisintegrent to give the faster release of
pioglitazone. The tablets were prepared by wet granulation method and by direct
compression. Granules were evaluated for precompression parameters and the tablets were
evaluated for post compression parameters.
Key Words: Bilayer tablets, Metformin Hydrochloride, pioglitazone, xanthum gum, guar
gum, gum tragacanth and crosscarmellose sodium.
Formulation and Evaluation of Floating Tablet of Metoprolol Succinateijtsrd
The aim of the present work is Formulation and Evaluation of Floating Tablet of Metoprolol Succinate. Metoprolol Succinate is a BCS class I drug used in the treatment of Angina pectoric, Heart attack, Hypertension and has short half life 3 7hours. In the present study it was planned to prepare sustained release floating tablets of Metoprolol succinate by using HPMC E5 and Gum Karaya excipients. The procured sample of drug was authenticated by pre formulation study like melting point, IR spectra, UV analysis were done. Results of pre formulation studies show that Metoprolol Succinate was pure and complies with standard. Prior to compression, the powder blend were evaluated for angle of repose, bulk density, tapped density, compressibility index, Hausners ratio. Results of pre formulation studies show that Metoprolol Succinate was pure and complies with standard. Formulations were evaluated for various evaluation parameters like hardness, thickness, weight variation, friability, drug content, floating lag time, floating time, swelling index and in vitro drug release. From the results of evaluation parameters it was observed that formulation F6 shows best results for floating lag time 4min floating time up to 12 hours and consistent drug release 96.15 as compared to other formulations. So formulation F6 was finalized as a optimized formulation for further study. On the basic of above finding it was concluded that sustained release floating drug delivery system was successfully achieved. Neeta. V. Jadhav | Prof. Mr. Prashant Khade | Dr. Ashok Bhosale "Formulation and Evaluation of Floating Tablet of Metoprolol Succinate" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-5 , August 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50409.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmaceutics/50409/formulation-and-evaluation-of-floating-tablet-of-metoprolol-succinate/neeta-v-jadhav
In the present study, a gastro retentive micro particulate system was formulated with different Polymers by using
solvent evaporation technique. A series of 8 formulations was prepared based on 23 Design of experiments. The
formulated microspheres were evaluated flow characteristics, Practical yield (up to 80 %) and Encapsulation
efficiency (up to 94%). Scanning electron Microscopy confirmed their porous and spherical structure and the
particles were of the Size range of (65-525 μm). The release of drug at 1 hour and 8 hours’ time points were
taken as the measurable parameters for running the DOE experiments. According to design space Hollow
Microspheres formulated with Drug in the range of 50 to 70 mg/unit, Ethyl cellulose 7 cps in the range of 145 to
150 mg/unit and HPMC 5 cps in the range of 0.4 to 2 mg/unit were observed to have the best floating
characteristics and in vitro dissolution profile as per the preset target product profile. Stability studies showed no
significant change in the drug content in the formulations at 3 months accelerated condition. In this study
concluded that a micro particulate floating dosage form of an anti-infective drug can be successfully designed to
give controlled release and improved oral bioavailability.
KEYWORDS
Gastro retentive system, Ciprofloxacin Hcl, Ethyl Cellulose 7 cps, HPMC 5cps, Hollow microspheres.
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).
Similar to DEVELOPMENT OF ITRACONAZOLE IMMEDIATE RELEASE PELLETS BY USING HPMC LOADED IN GELATIN CAPSULES (20)
Skin acts as a major target as well as a principal barrier for
topical/transdermal drug delivery. Despite the many advantages of this
system, the major obstacle is the low diffusion rate of drugs across the
stratum corneum. Several methods have been tried to increase the
permeation rate of drugs temporarily. One simple and convenient
approach is application of drugs in formulation with elastic vesicles or
skin enhancers. Vesicular system is one of the most convenient
methods for transdermal delivery of active substances and in that
ethosomes are most useful vesicular systems. Ethosomal carriers are
systems containing soft vesicles, composed of hydroalcoholic or
hydro/glycolic phospholipid in which the concentration of alcohols is
relatively high. The high concentration of ethanol brings increase in fluidity of lipids hence
increase in permeability of the skin and improves the drug penetration. Ethosomal
formulation may contain many drugs such as acyclovir, salbutamol, Insulin, cyclosporine,
fluconazole, minodixil, etc. These are prepared by hot method and cold methods. The size of
Ethosomal formulation can be decreased by sonication and extrusion method. The high
concentration of ethanol makes the ethosomes unique and useful for transcellular delivery,
delivery of hormones, anti-arthritis, anti-HIV etc. Thus, it can be a logical conclusion that
ethosomal formulation possesses promising future in effective dermal/transdermal delivery of
bioactive agents.
The aim of this research work involves the design and characterization of the drug being treated Itraconazole which is a Antifungal, Antiprotozoals, Antifungal Agents, Antiprotozoal Agents as a novel vesicular carrier system (transdermal drug delivery system) in the form of Ethosomes. These Ethosomes have been planned in order to overcome all the lacunae and various problems being confronted by the patients treated by Itraconazole namely half-life even though being a highly potent drug and also possessing very poor bioavailability (20-40%).The method of preparation of Itraconazole Ethosomes involves the use of various concentrations of Ethanol, phospholipids and polymers by the cold method (Sonication) which facilitates the suitable size reduction of vesicles. The designed Itraconazole Ethosomes have been characterized and validated by the parameters/techniques namely Visualization, Vesicle size and Zeta potential studies, Scanning Electron microscopy, Entrapment efficiency, Assay, Vesicle stability study, Solubility measurement, Penetration & Permeation studies and drug stability studies. Various Ethosomal formulations were prepared of different compositions namely IF1, IF2, IF3, IF4, IF5, IF6, IF7, IF8, and IF9. Among these the best formulation based on in-vitro drug release studies by dialysis membrane revealed that IF9 was adjudged the best from among the sonicated Ethosomes. However ethosomes prepared by sonication method were more uniform and small in size which is essential for skin penetration. While comparing the entrapment efficiency, ethosomes containing 30% w/w methanol and prepared by sonication showed highest value respect to all other formulation; so it is concluded ethosomal prepared by sonication and containing 30 % w/w methanol as the best formulation considering all other aspects. The highest value of transdermal flux for sonicated ethosomes containing 30% w/w methanol is the indication of complete and rapid penetration through the skin may be because of tiny vesicular size. This is an encouraging observation for drugs which are poorly absorbed from skin. When effect of sonication was compared on ethosomal formulation, IF8 formulation possessed better or suitable characteristics (smaller size, uniform size, distribution, highest entrapment efficiency).
INTRODUCTION: This research aims at enlightens and emphasizing the most prevailing disease conditions and disorders which are most common in mahabubnagar locality ,were category A(augmented) type ADR are more followed by type C(continous).
METHODS: A retrospective research study was conducted using Naronji's and WHO standard scales have been used to categorise the ADR into category A, category B, category C and category D for the given cases.
Epidemological data like age, ADR, and disease condition prevailing in hospitalised patients are noted and categorised department wise.
ABSTRACT
The traditional medicine involves the use of different plant extracts or the bioactive constituents. The study
such as ethno medicine keenly represents one of the best avenues in searching new economic plants for
medicine. This type of study provides the health application at affordable cost. The present study carried out to
find out the phytochemical constituents in the Ficusracemosa leaves. The materials were grained and extracted
with benzene, ethanol, ethyl acetate, and methanol and petroleum ether. Photochemical analysis was carried
out according to standard procedures. Sugar, protein, alkaloids, flavonoids, sterols and glycoside were found
to be present in the extracts.
KEY WORDS
Ficusracemosa (linn.)moraceae, Pharmacological and Phytochemical studies.
Skin acts as a major target as well as a principal barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been tried to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Vesicular system is one of the most convenient methods for transdermal delivery of active substances and in that ethosomes are most useful vesicular systems. Ethosomal carriers are systems containing soft vesicles, composed of hydroalcoholic or hydro/glycolic phospholipid in which the concentration of alcohols is relatively high. The high concentration of ethanol brings increase in fluidity of lipids hence increase in permeability of the skin and improves the drug penetration. Ethosomal formulation may contain many drugs such as acyclovir, salbutamol, Insulin, cyclosporine, fluconazole, minodixil, etc. These are prepared by hot method and cold methods. The size of Ethosomal formulation can be decreased by sonication and extrusion method. The high concentration of ethanol makes the ethosomes unique and useful for transcellular delivery, delivery of hormones, anti-arthritis, anti-HIV etc. Thus, it can be a logical conclusion that ethosomal formulation possesses promising future in effective dermal/transdermal delivery of bioactive agents.
ABSTRACT Gliclazide microspheres were prepared by ionotropic gelation method using bioadhesive polymers such as sodium alginate, carbopol 934, carbopol 971, HPMC K4M in different ratios. Totally twelve different formulations of gliclazide were prepared by using the above polymers. The microspheres were characterized for drug content, entrapment efficiency, swelling index, mucoadhesive property by In vitro wash-off test and in-vitro drug release. The results of this investigation indicate that ionic cross linking technique Ionotropic gelation method can be successfully employed to fabricate Model drug microspheres. Micrometric studies revealed that the mean particle size of the prepared microspheres was in the size range of 512-903 μm and are suitable for bioadhesive microspheres for oral administration. The in-vitro mucoadhesive study demonstrated that microspheres of Model drug using sodium alginate along with Carbopol 934 as copolymer adhered to the mucus to a greater extent than the microspheres of Model drug using sodium alginate along with Carbopol 971 and HPMC K4Mas copolymers. Analysis of drug release mechanism showed that the drug release from the formulations followed non-Fickian diffusion and the best fit model was found to be Korsmeyer-Peppas. Based on the results of evaluation tests formulation coded T4 was concluded as best formulation. Keywords: Bioadhesive Microspheres, Gliclazide, Ionotropic gelation method.
Abstract:
The Chronopharmacotherapy the drug administration is synchronised with circadian rhythms Formulation development of Microspheres is more reliable formulation as compare to single type dosage formulation due to it avoids dose dumping, as per required drug release profile is achieved For microspheres many polymers are used such as albumin, gelatine, starch, Eudragit, Polyacrylamide (“PAM”) these material loading capacity is high. Micro sponges which are Spherical are called as micro-balloons. Due to its hollow structure it shows good floating properties. In these systems use of Carbon-dioxide (CO2) as gas generating system which are used for floating purpose. The objective of present investigation is to prepared and evaluate a floating pulsatile drug delivery system of Aceclofenac. The strategy adopted for microspheres containing Aceclofenac as a material were prepared by emulsion solvent diffusion technique. Drug and polymer were mixed in dichloromethane and ethanol at 1:1 ratio. The drug and polymer solution were poured in water 50% W/V polyvinyl alcohol maintained at 30-40 C and the solution was stir at 500rpm using mechanical stirrer, The microspheres obtain were washed repeatedly with water until free from poly vinyl alcohol. The developed formulations were evaluated yield of floating microspheres particle size and shape, drug entrapment efficiency in-vitro evolution of floating ability, in-vitro drug release study. On the basis of these evolution parameters it was found that optimised floating pulsatile release formulation F7 showed higher drug entrapment efficiency floating time 6.8 minutes and the drug and polymer 32 1:3 ratio the particle size was increased.
Key Words: Chronopharmacotherapy, Floating pulsatile drug delivery, Aceclofenac.
ABSTRACT
The aim of the present research work was to enhance the solubility of
Carvedilol by solid dispersion method and to formulate a mouth
dissolving tablet. Drugs are more frequently taken by oral
administration. The solubility of Carvedilol enhanced with different
ratios of PVP by the solvent evaporation method .In-vitro release
profile of solid dispersion obtained in SGF without enzymes and Ph
6.8 phosphate buffer indicate that 100% drug release found within 20
min. These solid dispersion were directly compressed into tablets using
Crospovidone, sodium starch glycol ate, croscarmellose sodium and
polyacrylic potassium in different concentrations as a super
disintegrants. The prepared tablets containing the solid dispersion of
Carvedilol having sufficient strength of 2.5-4 kg/cm2. The
disintegrated in the oral cavity with in 21 sec. contain Crospovidone
(5%) as super disintegrant.
KEYWORDS: Carvedilol, PVP, Super Disintegrants, Mouth Dissolving Tablet.
ABSTRACT
Carvedilol is a cardiovascular drug of multifaceted therapeutic potential, with beta-blocker and vasodilatative activity. These actions confer to the above mentioned beta blocker some beneficial properties on several processes involving cardiovascular system. Carvedilol provides hemodynamic, ant ischemic, anti-proliferative and antiarrhytmic benefits, for its antioxidant neuro humoral and electrophysiological effects. All these actions provide the basis for usefulness of the drug in the treatment of hypertension, coronary heart disease, and congestive heart failure. In this review we report the beneficial properties of Carvedilol and we analyze the rational clinical use of this beta blocker taking special attention on recent clinical trial in heart failure where it appears evidence supporting an important, favorable effect of the drug.
KEYWORDS: Carvedilol, Hypertension, Coronary disease, Hearth failure.
A new precise accurate and reliable validated method for the determination of Capecitabine was developed by using
reverse phase high performance liquid chromatography in pharmaceutical dosage forms. Spectrophotometer
determination was carried out at an absorption maximum of 240nm by using methanol. The linearity was over the
concentration range of 20-120 μg/ml with correlation coefficient 0.999. Chromatographic separation was carried
out by using a mobile phase of methanol: Acetonitrile: water (80:20:80 V/V) on Waters 2487 dual absorbance
column in an isocratic mode at a flow rate of 1.1 ml/min with UV detection at 240 nm. The developed methods were
found to be precise and accurate for the estimation of Capecitabine in pharmaceutical dosage forms and could be
used for routine analysis.
Keywords: Capecitabine, RP-HPLC, Spectrophotometry, Waters 2487 dual absorbance detector, Nova pack 300 ×
3.9mm 5μ as column, 240nm
The global prevalence of obesity is increasing rapidly and high dietary fat intake is major risk factor for the development of obesity. The present study was taken undertaken to evaluate the effect of Argyreia Nervosa Burn.F leaf ethanol extract on serum lipid profile in Wistar male albino rat fed with high fat diet and to compare it with a standard hyperlipidemic drug Sibutramine (10mg/kg). Fifty four health Wistar albino male rats were randomized in to 9 groups of 6 animals each. The groups were followed as follows Group I: Sham operated Normal (Normal Diet), Group II: Control (High fat diet), Group III: Sibutramine 10 mg/kg + HFD, Group IV: EEAN (100mg/kg) + HFD, Group V: EEAN (200mg/kg) +HFD, Group VI: EEAN
(400mg/kg) + HFD, Remaining groups have received different types of extracts at various doses. Lipid profile in serum with high triglyceride (TG) and cholesterol levels were significantly reduced by treatment of 0.5g/day A. nervosa. The A. nervosa markedly lowers the levels of serum cholesterol and VLDL. The present investigation shows that all triton induced rats
displayed hyperlipidemia as shown by their elevated levels of serum and liver cholesterol, triglyceride, PL, VLDL, LDL and the reduction in the HDL level. It can be concluded that 0.5g/day of A. nervosa treatment was effective in reduction of cholesterol, PL, TG, VLDL, LDL and HDL in a dose dependant manner.
Diabetes mellitus is among the most common disorder in developed and
developing countries, and the disease is increasing rapidly in most parts
of the world. It has been estimated that up to one-third of patients with
diabetes mellitus use some form of complementary and alternative
medicine. Alstonia scholaris is a plant of family Apocynaceae and has a
great medicinal importance. It is widely used by tribal people to treat
various diseases and ailments. The present communication deals with
the organoleptic and preliminary physico-phytochemical studies of the
stem bark of the plant. The organoleptic study was done according to
the W.H.O. guidelines for medicinal plants. Alstonia scholaris is a plant
that has been used in popular medicine for the treatment of the diabetes.
It is native to the Indian subcontinent, Indomalaya, Malaysia, and
Australasia. This has been investigated based on amerolative properties
of bioactive compounds of Alstonia scholaris stem bark extract up on
alloxan induced diabetic rats. The blood glucose levels were increased
significantly. Ethanolic stem bark extract of A. scholaris was given to
the diabetic rats in daily dose of 450mg/ kg of body weight (21 days). In
diabetic rats of blood glucose levels decreased highly significant
(p<0.005). The reduction in blood glucose can be used as a marker in
the evaluating the severity of diabetes.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
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Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
DEVELOPMENT OF ITRACONAZOLE IMMEDIATE RELEASE PELLETS BY USING HPMC LOADED IN GELATIN CAPSULES
1. 1
Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
e- ISSN 0976 - 3651
Print ISSN 2229 - 7480
International Journal of Biological
&
Pharmaceutical Research
Journal homepage: www.ijbpr.com
DEVELOPMENT OF ITRACONAZOLE IMMEDIATE RELEASE
PELLETS BY USING HPMC LOADED IN GELATIN CAPSULES
CH. Ananda kumar*, M. Prathap1
, P. Venketeswararao2
, A.M.S. Sudakar babu1
,
R.V.V. Narendra babu1
, M. Sajeev shanthi3
*1
Department of Pharmaceutics, A.M.Reddy Memorial College of Pharmacy, Narasaraopet, Guntur, Andhra Pradesh, India.
2
Department of Pharmaceutical Chemistry, A.M.Reddy Memorial College of Pharmacy, Narasaraopet, Guntur,
Andhra Pradesh, India.
3
Department of Pharmaceutics, Nirmala College of Pharmacy, Atmakuru, Guntur, Andhra Pradesh, India.
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.
INTRODUCTION
From time immemorial, drugs have been an
inseparable part of mankind’s history since they fulfill one
of our most basic necessities. To administer these drugs in
an appealing and palatable form and in the required
amount and rate, they have to be developed into an
acceptable dosage form. Thus, the concept of formulation
development was evolved, resulting in solid, liquid and
semi-solid dosage form (Thomas N. Tozer et al., 2001)
Solid dosage forms
Solid dosage forms are widely prevalent due to
Corresponding Author
CH. Ananda kumar
Email: anand33.chettupalli@gmail.com
their age-old application. Especially, oral solid
formulations hold a high potential as they serve to be most
convenient for the administration of drugs. These have
been developed into a wide range of formulations from
conventional dosage forms for immediate release of the
drug to controlled release dosage forms for the constant
rate of drug release. Oral rouse is the most convenient and
commonly used method of drug delivery. More than 50%
of drug delivery systems available in the market are oral
drug delivery systems. They offer convenience and ease of
administration, greater flexibility in dosage form design
and ease of production and low cost. Pharmaceutical oral
solid dosage forms have been used widely for decades
mainly due to their convenience of administration and their
suitability for delivery of drugs for systemic effects. The
most commonly used pharmaceutical solid dosage forms
today include granules, pellets, tablets and capsules. A
IJBPR
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Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
simplified flow chart of the relationship of pharmaceutical
dosage forms can be shown as
Oral drug delivery has been known for decades as
the most widely utilized route of administration among all
the routes that have been explored for the systemic
delivery of drugs via various pharmaceutical products of
different dosage forms. Ideally a drug to provide desired
therapeutic action should arrive rapidly at the site of action
in optimum concentration, remain there for the desire time,
be excluded from other site. The fact that absorption rate of
drug into the body can be decreased by reduction of the
rate of release of the drug from the dosage form is one of
the most recent and interesting result of pharmaceutical
research.
Once a day or at the most twice a day formulation
is a holy grail of sorts for scientists working with oral
dosage forms. A sustained release preparation that makes
once or twice daily administration of drug possible might
be an advantageous dosage form, especially in long-term
therapy.
This ideal dosing regimen, which enhances patient
compliance and helps guard against overdosing and side
effects, is made possible by controlled release delivery
systems, whicuse a variety of mechanisms to deliver and
maintain the drug at a certain level in the patient’s blood
stream.
Immediate release dosage form
Conventional immediate release drug delivery
system are based on single or multiple-unit reservoir or
matrix system, which are designed to provide immediate
drug levels in short period of time. Immediate release drug
delivery is desirable for drugs having long biological half-
life, high bioavailability, lower clearance and lower
elimination half-life. But main criterion for immediate
release dosage form is poor solubility of the drug and need
the immediate action of drug to treat any unwanted defect
or disease.
The correct selection and balance of excipients
and processes in solid dosage formulations are designed
either for improving the micromeritic or macromeritic
properties of materials during manufacture and/or for
providing a desired drug delivery system (Bianchini R. et
al., 1992). The most commonly used pharmaceutical
immediate release solid oral dosage forms today include
tablets, capsules, granules and pellets (Ansel CH et al.,
1995).
MATERIALS AND METHOD
Materials
Itraconazole and HPMC were received as gift
samples from Ra chem Ltd, Ahmedabad, India.
Polyethylene glycol e20000 was a Gift sample from
Clarient. Sugar spheres were a Gift sample from Shiva
shakti. Dichloro methane was a Gift sample from Merck,
Ethanol was a Gift sample from Merck.
Method
Preparation of ranitidine hydrochloride floating tablets
Step: 1 Drug Loading
Dispense all the materials as per manufacturing
formulae. Shift the materials by using 50# mesh Filter the
required quantity of dichloro methane and ethanol and mix
it. Add hypremellose in above mixer and stir well still to
get clear solution, after add itraconazole to above solution
and mix it same stirring condition until get homogenous
mixer. After completion of above process filter the solution
by using #100 mesh. Transfer the core(sugar spheres) into
the FBP and coat with the above prepared Coating solution
Adjust the spray rate, inlet air temperature are in such a
way that the drug coated pellets reaches a temperature of
about 380
C-400
C. Over wetting of the drug coated pellets
to be avoided as it may cause agglomeration. After
complete quantity of the coating solution remove the
pellets from FBP and kept for drying in a tray dryer. The
dried pellets are sized on a sifter to remove agglomerates,
broken pellets and fine powder. After checking the weight
of the pellets and noting down the yield it should be
packed in a double polythene bags, labeled, and securely
tied. This is ready for seal coating.
Step II: Seal Coating of Pellets
Dispense all the materials as per manufacturing
formulae. Shift the materials by using 50# mesh Filter the
required quantity of dichloro methane and ethanol and mix
it. Add PEG 20000 in above mixer and stir well still to get
clear solution. After completion of above process filter the
solution by using #100 meshes. Transfer the drug loaded
pellets into the FBP and coat with the above prepared
Coating solution. Adjust the spray rate, inlet air
temperature are in such a way that the drug coated pellets
reaches a temperature of about 380
C-400
C. Over wetting
of the drug coated pellets to be avoided as it may cause
agglomeration. The dried pellets are sized on a sifter to
remove agglomerates, broken pellets and fine powder.
After checking the weight of the pellets and noting down
the yield it should be packed in a double polythene bags,
labeled, and securely tied.
Preformulation Studies
Interparticulate interactions that influence the
bulking properties of a powder with powder flow. A
comparison of the bulk density and tapped density can give
a measure of the relative importance of this interaction in a
given powder; such a comparison is often used as an index
of the ability of the powder to flow. The bulk density and
tapped density was found to be 0.248 g/ml and 0.328 g/ml
respectively.
The drug and polymers were evaluated for Bulk
density, Compressibility index, Hausner’s ratio and Angle
of repose, Melting point, Solubility. Found that all the
parameters are within the official specifications.
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Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
Compatibility studies
Compatibility studies were conducted to
investigate and predict physicochemical interaction
between drug substance and excipients and therefore to
select suitability of chemically compatible excipients.
Preformulation studies are carried out with the objective of
ascertaining the incompatibility of the excipients used in
the existing formulation and to avoid any excipient, which
is incompatible with the drug in the final formulation.
The compatibility studies were carried out at
250
C/60% RH and 400
C/75% RH for, 2 and 4 weeks. With
respect to physical and chemical aspects, they were tested
and there is no drug-excipients interactions are observed.
Compatibility studies were performed using DSC.
The DSC of pure drug and physical mixture of drug and
polymer were studied. The peaks obtained in the graph of
each formulation correlates with the peaks of drug. This
indicates that the drug was compatible with the formulation
components.
Evaluation Study of Capsules
Content uniformity test
The amount of active ingredient determined by
assay is within the range of 85% to 115% of the label claim
for 9 of 10 dosage units assayed with no unit outside the
range of 70% to 125% of label claim. Additional tests are
prescribed when two or three dosage units are outside of
the desired range but within the stated extremes.
Weight variation test
Individual weights of 20 capsules were taken and
the average weight was calculated by using the following
formula.
(Weight of capsule-Average weight)
Weight variation = --------------------------------------- ×100
Average weight of capsules
Weight variation should not be more than 5 %.
Lock length (The United States Pharmacopeia. Twenty-
third revision) It was tested by using vernier calipers.
Moisture permeation test
The USP requires determination of the moisture
permeation characteristics of single unit and unit dose
containers to assure their suitability for packing capsules.
The degree and rate of moisture penetration is determined
by packing the dosage unit together with a color revealing
desiccant pellet, exposing the packaged unit to known
relative humidity over a specified time, observing the
desiccant pellet for color change (indicating desiccating
absorption of moisture) and comparing the pre and post
weight of the packaged unit and also by the Karl Fisher
titration equipment.
Disintegration
The compendial disintegration test for hard and
soft capsules follows the same procedure and uses the
same apparatus described later in this chapter for uncoated
tablets. The capsules are placed in the basket rack
assembly, which is repeatedly immersed 30 times per
minute into a thermostatically controlled fluid at 37ºC and
observed over the time described in the individual
monograph. To fully satisfy the test the capsules
disintegrate completely into a soft mass having no palpably
firm core, and only some fragments of the gelatin shell
(Paterakis PG et al., 2002).
Stability Study
For all the pharmaceutical dosage forms it is
important to determine the stability of the dosage form.
This will include storage at both normal and exaggerated
temperature conditions, with the necessary extrapolations
to ensure the product will, over its designed shelf life,
provide medication for absorption at the same rate as when
originally formulated. The design of the formal stability
studies for the drug product should be based on the
knowledge of the behavior and properties of the drug
substance and formal stability studies on the drug
substance. Specification which is list of tests, reference to
the analytical procedures and proposed acceptance criteria,
including the concept of different acceptable criteria for
release and shelf life specifications, is addressed in ICH CS
L6AS and IS6B.
Figure 1. DSC Graph of pure Itraconazole
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Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
Figure 2. DSC for Itraconazole and pvpk 29/32
Figure 3. DSC Graph for Itraconazole and HPMC
Figure 4. DSC Graph for Itrconazole and HPC
Figure 5. Release Profile of Formulated Itraconazole Figure 6. Release Profile of Formulated Itraconazole
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Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
Figure 7. Release Profile of Marketed Sample Vs Formulation F4
Table 1. Formula for Itraconazole 100 mg capsule
Table 2. Compatibility study results
Table 2. Results of Compatibility Study for Itraconazole blend
Drug: Polymer
Ratios
1:1 1:3 3:1
ITC: PVP K29/32 Amorphous Amorphous Endothermic transition at 164.35°C
ITC: HPC Endothermic transition at 165.05°C Amorphous Endothermic transition at 166.20°C
ITC: HPMC 606 Amorphous Amorphous Endothermic transitionat 164.67°C
Table 3. Physical property of Itraconazole
Bulk density(gm/ml) Tapped Density (gm/ml) Compressibility Index Hausner’s Ratio Angle of repose
0.248 0.328 24.39 % 1.322 36.040
Evaluation of Capsules
Table 4. Weight variation of Itraconazole
S.No Ingredients F1 F2 F3 F4 F5 F6
Drug Loading
1 Itraconazole 99.82mg 99.82mg 99.82mg 99.82mg 99.82mg 99.82mg
2 Sugar Pellets (#20- #24) 239.2mg 226.5mg 203.1mg 192.0mg 182.9mg 196.5mg
3 HPMC E-5 99.82mg 120.2mg 135.9mg 150.7mg 159.3mg 153.8mg
4 Dichloro methane 45ml 45ml 45ml 45ml 45ml 45ml
5 Ethanol 30ml 30ml 30ml 30ml 30ml 30ml
Seal Coating
6 P.E.G-20000 18.4mg 13.8mg 20.75mg 18.4mg 18.4mg 11.5mg
7 Dichloro methane Q.S Q.S Q.S Q.S Q.S Q.S
8 Ethanol Q.S Q.S Q.S Q.S Q.S Q.S
S.No Composition details Observation
Storage condition/duration
Initial 40 / 75 % RH 25 2°C,60°C
2W 4W 2W 4W
1 API alone (D) White powder NCC NCC NCC NCC
2 D+HPMC White powder NCC NCC NCC NCC
3 D + HPC Off white CC CC CC CC
4 D + PVPK white powder NCC NCC NCC NCC
5 D+ SUGAR SPHERES White powder NCC NCC NCC NCC
S.No Parameter F1 F2 F3 F4 F5 F6
1 Weight variation 462.2 455.6 456.3 462.2 468.1 440.6
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Ananda Kumar CH. et al. / International Journal of Biological & Pharmaceutical Research. 2012; 3(7): 1-7.
Table 5. Content uniformity of Itraconazole
S.No F1 F2 F3 F4 F5 F6
Strength 460 mg 103.9% 105.7% 103.0% 102.5% 104.2% 95.7%
Table 6. Disintegration test of Itraconazole
Table 7. Moisture content of Itraconazole
Table 8. Release Profile of Formulated Itraconazole
In vitro dissolution Studies
The release rate of Ranitidine hydrochloride
floating tablet was determined using INDIAN
PHARMACOPEIA (IP) 96; Dissolution test apparatus
(paddle method). The dissolution test was performed using
900mL of 0.1N Hcl, at 37± 0.5ºC and 75 rpm. 10ml of the
solution was withdrawn from the dissolution apparatus
hourly for 10 hours and the sample were replaced with
fresh dissolution medium. The sample were filtered
through membrane filter and diluted with suitable
concentration with 0.1N Hcl. Cumulative percentage drug
release was calculated using an equation obtained from
standard curve.
RESULTS
Physical properties of Itraconazole blend
Physical properties of Itraconazole and polymers like
bulk density, tapped density, compressibility index and
Hausner’s ratio and angle of repose result is shown below
tab.
DISCUSSION AND CONCLUSION
The active pharmaceutical ingredient
ITRACONAZOLE was subjected to Preformulation study,
which encompasses the “Accelerated drug excipient
compatibility study”, and the results obtained with selected
excipients showed good compatibility with HPMC and
PVPK, but solubility of HPMC is more in selected solvents
when compare with PVPK. That’s why we selected HPMC
for solubilizer in the formulation. The stability of the
capsules and pellet was determined by conducting
“Accelerated stability testing” in 40°C ± 2°C / 75% ±
5%RH and 25ºC ± 2 ºC/ 60% RH ± 5% RH,
30ºC±2ºC/65±5% RH conditions for 3 months as per ICH
guidelines in HDPE containers. Finally after the duration,
the product was analyzed for content uniformity, assay,
and disintegration and dissolution studies. By the stability
studies, the formulated Itraconazole immediate release
capsules and pellets proved to be stable throughout the
period of the storage. The release was found nearer in the
case of pellets loaded in capsules. And dissolution profile
of Itraconazole immediate release capsules were compared
with that of innovator (SPORANOX). The release was
found similar to that of innovator. So the prepared product
was said to be equivalent with innovator. The release in
the starting hours is increasing by increasing the
concentration of Hpmc in the formulation F4 and it is
optimized. Even though Itraconazole solution form is
available in market the formulation of F4 was shows better
results with innovator product and the formulation process
will be easy, safe and effective.
The present study concluded that immediate
release pellets in capsule of formulation F4 has relevant
drug release rate rather than innovator and it has better
stability, Bioavailability than the innovator.
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S.No Parameter F1 F2 F3 F4 F5 F6
1 Disintegration time in min. 4.30 4.50 4.40 5.10 4.50 4.50
S.No Parameter F1 F2 F3 F4 F5 F6
1 Moisture content 3.2% 2.9% 3.2% 3.1% 3.3% 2.9%
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0 0.00 0 0 0 0 0 0
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