In the present study, a newly innovative drug delivery system of biphasic Metronidazole (MTZ) tablet has been studied. An attempt was made to improve the patient’s adherence and the potential clinical outcomes by reducing the dosing frequency by formulating bilayer tablets containing Metrodinazole. Each bilayer tablet is composed of a sustained release (SR) layer and an immediate release (IR) layer for rapid drug release. Five different formulations of bilayer tablets were formulated using HPMC as hydrophilic polymer to retarded the drug release and the effect of Starch and MCC on the release profile were evaluated. Wet granulation method was used to prepare granules of the immediate and sustained release layers. The tablets were evaluated for their physical parameters and all valuesobtained found to be within the acceptable limits. The dissolution test has been carried out using the USP type II rotating paddle. Collected samples were analyzed using the high performance liquid chromatography. The mechanisms of Metrodinazole release from the sustained release layer were fitted into zero-order, first order, Higuchi, Hixon- Crowell model and Korsmeyer-Peppas release model. The results of the dissolution profiles showed that the drug release from the sustained release layer varied depending on the amount of HPMC and the presence of Starch or MCC. The kinetics of the release of MTZ from the different formulations showed good fitting with Higuchi model with correlation coefficients (R2) of 0.9965 - 0.9985. From values obtained for the diffusional exponent, n, Korsmeyer-Peppas equation observed that for all the formulations n value ranged from 0.4662 to 0.5370, and this demonstrates that the release mechanism followed non-Fickian type of release ( anomalous transport).
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.
Development and evaluation of a novel twice daily cup core metformin hydrochl...SriramNagarajan19
The study was undertaken with an aim to formulate develop and evaluation of a novel twice daily core cup of Metformin hydrochloride(Antidiabetic drug) tablets using different grades and weight of HPMC polymers as release retarding agent. Granules were evaluated for tests Bulk density, tapped density, Hausner ratio before being punched as tablets. Tablets were tested for weight variation, thickness, hardness and friability as per official procedure. F-2 was found to be 73.90. From the above results and discussion it is concluded that formulation of Cup core tablet of containing Metformin hydrochloride HPMC K 4M & 215: 230 (in mg) can be taken as an ideal or optimized formulation of sustained release tablets for 12hour release as it fulfills all the requirements for sustained release tablet and our study encourages for the further clinical trials on this formulation. The core in cup tablets of Metformin hydrochloride were prepared by wet granulation method, they were evaluated for weight variation, friability, hardness, and thickness for all batches (F1 – F9). No significant difference was observed in the weight of individual tablets from the average weight. The weight variation tests were performed according to the procedure given in the pharmacopoeia. In a weight variation test, pharmacopoeial limit of tablet for percentage deviation is 5%. The average percentage deviation of all tablet formulation was found to be within the pharmacopoeial limit and hence all formulation passed the test for uniformity of weight.
Aim: This diploma thesis focused on the study of the influence of two types of high-shear
mixers as well as the effect of poly(meth)acrylate concentrations on the properties of
prepared granules and consequently matrix tablets.
Methods: Caffeine was employed as the model drug and matrix tablets were prepared via
the wet granulation process using two different high-shear mixers either Stephan UMC5 or
Rotolab mixer. Eudragit® NM 30D was used in various concentrations as a wet granulation
agent for time controlled drug release with low permeability and pH independent swelling.
In addition, lactose monohydrate was added as indifferent soluble filler, magnesium
stearate served as the antiadhesive excipient and colloidal silica was added for flowability
improvement. Matrix tablets were evaluated for mass, content and dosage uniformity,
uniformity of dosage units, friability, hardness and dissolution according to Ph. Eur.
Results - Conclusions: All prepared tablets exhibited sustained drug release. The
employment of different mixers for sustained matrix tablets preparation did not
significantly influence the release profile of caffeine (Eudragit® NM concentrations 9-
14%), except when the lower Eudragit® NM concentration (7%) was used for granulation.
Furthermore, Eudragit® NM concentrations (7 – 14% per tablet) did not significantly affect
the release profile of caffeine from matrix tablets, neither in the Stephan UMC5 nor the
Rotolab mixer.
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.
Development and evaluation of a novel twice daily cup core metformin hydrochl...SriramNagarajan19
The study was undertaken with an aim to formulate develop and evaluation of a novel twice daily core cup of Metformin hydrochloride(Antidiabetic drug) tablets using different grades and weight of HPMC polymers as release retarding agent. Granules were evaluated for tests Bulk density, tapped density, Hausner ratio before being punched as tablets. Tablets were tested for weight variation, thickness, hardness and friability as per official procedure. F-2 was found to be 73.90. From the above results and discussion it is concluded that formulation of Cup core tablet of containing Metformin hydrochloride HPMC K 4M & 215: 230 (in mg) can be taken as an ideal or optimized formulation of sustained release tablets for 12hour release as it fulfills all the requirements for sustained release tablet and our study encourages for the further clinical trials on this formulation. The core in cup tablets of Metformin hydrochloride were prepared by wet granulation method, they were evaluated for weight variation, friability, hardness, and thickness for all batches (F1 – F9). No significant difference was observed in the weight of individual tablets from the average weight. The weight variation tests were performed according to the procedure given in the pharmacopoeia. In a weight variation test, pharmacopoeial limit of tablet for percentage deviation is 5%. The average percentage deviation of all tablet formulation was found to be within the pharmacopoeial limit and hence all formulation passed the test for uniformity of weight.
Aim: This diploma thesis focused on the study of the influence of two types of high-shear
mixers as well as the effect of poly(meth)acrylate concentrations on the properties of
prepared granules and consequently matrix tablets.
Methods: Caffeine was employed as the model drug and matrix tablets were prepared via
the wet granulation process using two different high-shear mixers either Stephan UMC5 or
Rotolab mixer. Eudragit® NM 30D was used in various concentrations as a wet granulation
agent for time controlled drug release with low permeability and pH independent swelling.
In addition, lactose monohydrate was added as indifferent soluble filler, magnesium
stearate served as the antiadhesive excipient and colloidal silica was added for flowability
improvement. Matrix tablets were evaluated for mass, content and dosage uniformity,
uniformity of dosage units, friability, hardness and dissolution according to Ph. Eur.
Results - Conclusions: All prepared tablets exhibited sustained drug release. The
employment of different mixers for sustained matrix tablets preparation did not
significantly influence the release profile of caffeine (Eudragit® NM concentrations 9-
14%), except when the lower Eudragit® NM concentration (7%) was used for granulation.
Furthermore, Eudragit® NM concentrations (7 – 14% per tablet) did not significantly affect
the release profile of caffeine from matrix tablets, neither in the Stephan UMC5 nor the
Rotolab mixer.
Preparation and Evaluation of Metformin Transdermal PatchesSunil Vadithya
Preparation and Evaluation of Metformin Transdermal Patches, Preparation and Evaluation of Metformin Transdermal Patches, Preparation and Evaluation of Metformin Transdermal Patches
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).
Matrix dosage forms in pharmaceutics (pharmaceutical dosage forms)YashYuvaraj
various sources from#detail of matrix dosage forms!!
1formulative pharmacy and biopharmaceutics
@pharmaceutical dosage forms
department of pharmaceutics
Formulation and evaluation of gastroretentative floating sustained releasedme...Sagar Savale
The Metformin HCL Gastroretentative Floating Sustained released Tablet is formulated by the Wet
Granulation technique. This Tablet is containing both Effervescent as well as Non Effervescent system. The
HPMC K 100 Swellable polymer is responsible for the Floating. (Non-Effervescent system) and The Sodium
Bicarbonate is responsible for the effervescent system. A combination of HPMC K 100 and Xanthum Gum
shows better sustained release activity. The Prepared Gastroretentative Floating Sustained released Tablet is
Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index and, weight variation test,
friability test and in vitro study, Total Floating Time. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The weight variation and friability these values are
within the pharmacopeia limit. The in vitro Dissolution studies show Maximum percentage of release of drug
(99.25) within end of 8 Hours.
ABSTRACT
Purpose: The main objective of present research investigation is to formulate the sustained release tablet of
Simvastatin using 32
factorial design. Simvastatin, an antihyperlipidemic agent, belongs BCS class-II agent.
Methods: The SR tablets of Simvastatin were prepared employing different concentrations of HPMCK4M and
SCMC in different combinations by wet granulation technique using 32
factorial design. The concentration of
Polymers , HPMCK4M and SCMC 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. Results and Discussion: 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, slope & regression coefficient were calculated. Polynomial equations were developed for t10%,
t
50%, t75%, t90%. Validity of developed polynomial equations were verifiedby designing 2 check point formulations
(C1
, C2
). According to SUPAC guidelines the formulation (F4
) containing combination of 17.5% HPMCK4M and
30% SCMC, is the most similar formulation (similarity factor f2
= 89.652, dissimilarity factor f1
= 1.6424 & No
significant difference, t= 0.00558) to marketed product (ZOCOR). Conclusion: The selected formulation (F4
)
follows Zero order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion
(n= 0.963).
Keywords: Simvastatin, 32 Factorial Design, Sustained Release Tablet, HPMCK4M ,SCMC, SUPAC, Non-Fickian
Diffusion Mechanism, Zero order kinetics
Design, optimization and in vitro evaluation of gastroretentive hollow micros...SURYAKANTVERMA2
To modify the GIT time is one of the main challenge in the development of oral controlled drug delivery system.
Gastric emptying of pharmaceutical dosage form is highly variable and dependent on the dosage form and the fed/fasted state of the stomach.
Normal gastric residence time usually ranges between 5 minutes to 2 hours.
І під кінець року хочемо вас ознайомити з результатами опитування "Потреби місцевої громади ", до якого ви долучилися і за що вам величезне Дякуємо!
Чудова можливість завдяки Isar Ednannia та Київському Міжнародному Інституту Соціології. Дякуємо!
Preparation and Evaluation of Metformin Transdermal PatchesSunil Vadithya
Preparation and Evaluation of Metformin Transdermal Patches, Preparation and Evaluation of Metformin Transdermal Patches, Preparation and Evaluation of Metformin Transdermal Patches
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).
Matrix dosage forms in pharmaceutics (pharmaceutical dosage forms)YashYuvaraj
various sources from#detail of matrix dosage forms!!
1formulative pharmacy and biopharmaceutics
@pharmaceutical dosage forms
department of pharmaceutics
Formulation and evaluation of gastroretentative floating sustained releasedme...Sagar Savale
The Metformin HCL Gastroretentative Floating Sustained released Tablet is formulated by the Wet
Granulation technique. This Tablet is containing both Effervescent as well as Non Effervescent system. The
HPMC K 100 Swellable polymer is responsible for the Floating. (Non-Effervescent system) and The Sodium
Bicarbonate is responsible for the effervescent system. A combination of HPMC K 100 and Xanthum Gum
shows better sustained release activity. The Prepared Gastroretentative Floating Sustained released Tablet is
Evaluated In terms of bulk density, tapped density, angle of repose, Carr’s Index and, weight variation test,
friability test and in vitro study, Total Floating Time. The result associated in Optimized batch is good to
Satisfactory and having a good free flowing property. The weight variation and friability these values are
within the pharmacopeia limit. The in vitro Dissolution studies show Maximum percentage of release of drug
(99.25) within end of 8 Hours.
ABSTRACT
Purpose: The main objective of present research investigation is to formulate the sustained release tablet of
Simvastatin using 32
factorial design. Simvastatin, an antihyperlipidemic agent, belongs BCS class-II agent.
Methods: The SR tablets of Simvastatin were prepared employing different concentrations of HPMCK4M and
SCMC in different combinations by wet granulation technique using 32
factorial design. The concentration of
Polymers , HPMCK4M and SCMC 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. Results and Discussion: 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, slope & regression coefficient were calculated. Polynomial equations were developed for t10%,
t
50%, t75%, t90%. Validity of developed polynomial equations were verifiedby designing 2 check point formulations
(C1
, C2
). According to SUPAC guidelines the formulation (F4
) containing combination of 17.5% HPMCK4M and
30% SCMC, is the most similar formulation (similarity factor f2
= 89.652, dissimilarity factor f1
= 1.6424 & No
significant difference, t= 0.00558) to marketed product (ZOCOR). Conclusion: The selected formulation (F4
)
follows Zero order, Higuchi’s kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion
(n= 0.963).
Keywords: Simvastatin, 32 Factorial Design, Sustained Release Tablet, HPMCK4M ,SCMC, SUPAC, Non-Fickian
Diffusion Mechanism, Zero order kinetics
Design, optimization and in vitro evaluation of gastroretentive hollow micros...SURYAKANTVERMA2
To modify the GIT time is one of the main challenge in the development of oral controlled drug delivery system.
Gastric emptying of pharmaceutical dosage form is highly variable and dependent on the dosage form and the fed/fasted state of the stomach.
Normal gastric residence time usually ranges between 5 minutes to 2 hours.
І під кінець року хочемо вас ознайомити з результатами опитування "Потреби місцевої громади ", до якого ви долучилися і за що вам величезне Дякуємо!
Чудова можливість завдяки Isar Ednannia та Київському Міжнародному Інституту Соціології. Дякуємо!
Estimation of Net Interest Margin Determinants of the Deposit Banks in Turkey...inventionjournals
Banks, which are the irreplaceable intermediaries of the financial system, are financial institutions that significantly contributeto economic development. The basiccriterion that indicates the efficiency of the intermediation activities of banks is the net interest margins. These costs are assumed to be high for developing countries such as Turkey. The degree to which banks are willing to redeem the funds they collect as credit to the system is directly related to how low their intermediation costs will be. In this paper, it is aimed to estimate the net interest margin determinants of deposit banks in Turkey. Three different panel data models are used for this purpose. These are the Fixed and Random Static models and the GMM (Generalized Moment Models) Dynamic model
This study examines the calendar effects in five major ASEAN countries, namely Malaysia, Singapore, Thailand, Indonesia and the Philippines. Using the daily stock return series for data set ranging from 2011 to 2015, the study employs the OLS method to investigate the presence of month-of-the-year and dayof-the-week effects. The results suggest the presence of certain trend in the stock returns for all five countries. January effect was found in the Philippines while Malaysia and Singapore demonstrate the evidence that is consistent with the Monday effect. The presence of calendar effects in each country, though violates the very basic premise of EMH, cannot be construed as an avenue to exploit the market for possible abnormal profit since the transaction cost is not taken into consideration. Perhaps, the significant return will disappear once the transaction cost is incorporated in the study
The Relation between Organizational Silence and Personality Characteristics: ...inventionjournals
Organizational silence is defined as a form of behavior in which employees unwilling to speak up about organizational issues and concerns. Personality characteristics of employees is an impact on the behavior they exhibit silence. This situation emphasizes on the importance of individual differences in organizational silence. In organizations the work environment where employee can easily express views, ideas and suggestions, brings with positive results at the organizational level and individual besides this, organizational silence environment is considered to be an major obstacle to organizational and individual change and development. Therefore, the formation of organizational silence environment constitutes an undesirable situation by organizations. Thus, determination of the personality characteristics of employees is regarded important in terms of understanding of organizational silence behavior. With this research, it is aimed to determine the relations between the personality characteristics and organizational silence dimensions of individuals working in the hotel business operating in the tourism sector, in five-factor personality. For this purpose, the employees working in thermal hotels that are located in Kütahya region have been selected. As a result of the analyses conducted, in the organizational silence and the Big Five Personality traits of employees, the averages are close to each other and the highest average belongs to ProSocial silence and extroversion.
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.
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.
Formulation of an anti-inflammatory drug as fast dissolving tabletsIOSR Journals
The demand for mouth dissolving tablets has been growing during the last decade especially for elderly and children who have difficulties in swallowing. Ketorolac tromethamine is an effective anti-inflammatory agent that has been extensively used for the prevention of pain and inflammation associated with a wide variety of reasons. This study was aimed to form Ketorolac tromethamine mouth dissolving tablets by direct compression using superdisintegratants as crospovidone (CP) ,crosscarmellose sodium (CCS), and sodium starch glycolate (SSG) at concentrations of 3%, 6%, 9%, and 12%. The physical mixtures of the drug and the used excipients were evaluated for their micromeretric properties such as angle of repose, particle size, Hausner's ratio and % compressibility. Also, FTIR spectroscopy and DSC calorimetry were performed to indicate any possible interaction between the drug with the used excipients.All the prepared tablets were evaluated for their weight variation, thickness, hardness, wetting time, and disintegration time. Also in-vitro release study was done for all the prepared tablets using distilled deionized water as dissolution medium at 37.5± 0.5 c˚. Based on in-vitro release study and stability studies, G5 (contained 3% CCS) was found to be the promising formulae and subjected to further studies.
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).
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study
was to identify potential relationships between patient covariates and the methotrexate clearance estimates and
deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL
patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar
sittings.
Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population
and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2
(low-risk arm) or 5
gm/m2
(standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as
a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic
methotrexate clearance was calculated for each methotrexate dose
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.
microspheres,types, advantages and disadvantages,methods of preparation, evaluation or characterization of microspheres and applications of microspheres in various pharmaceutical fields.
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 Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC polymer (20)
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About
Indigenized remote control interface card suitable for MAFI system CCR equipment. Compatible for IDM8000 CCR. Backplane mounted serial and TCP/Ethernet communication module for CCR remote access. IDM 8000 CCR remote control on serial and TCP protocol.
• Remote control: Parallel or serial interface.
• Compatible with MAFI CCR system.
• Compatible with IDM8000 CCR.
• Compatible with Backplane mount serial communication.
• Compatible with commercial and Defence aviation CCR system.
• Remote control system for accessing CCR and allied system over serial or TCP.
• Indigenized local Support/presence in India.
• Easy in configuration using DIP switches.
Technical Specifications
Indigenized remote control interface card suitable for MAFI system CCR equipment. Compatible for IDM8000 CCR. Backplane mounted serial and TCP/Ethernet communication module for CCR remote access. IDM 8000 CCR remote control on serial and TCP protocol.
Key Features
Indigenized remote control interface card suitable for MAFI system CCR equipment. Compatible for IDM8000 CCR. Backplane mounted serial and TCP/Ethernet communication module for CCR remote access. IDM 8000 CCR remote control on serial and TCP protocol.
• Remote control: Parallel or serial interface
• Compatible with MAFI CCR system
• Copatiable with IDM8000 CCR
• Compatible with Backplane mount serial communication.
• Compatible with commercial and Defence aviation CCR system.
• Remote control system for accessing CCR and allied system over serial or TCP.
• Indigenized local Support/presence in India.
Application
• Remote control: Parallel or serial interface.
• Compatible with MAFI CCR system.
• Compatible with IDM8000 CCR.
• Compatible with Backplane mount serial communication.
• Compatible with commercial and Defence aviation CCR system.
• Remote control system for accessing CCR and allied system over serial or TCP.
• Indigenized local Support/presence in India.
• Easy in configuration using DIP switches.
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Author: Robbie Edward Sayers
Collaborators and co editors: Charlie Sims and Connor Healey.
(C) 2024 Robbie E. Sayers
Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC polymer
1. International Journal of Pharmaceutical Science Invention
ISSN (Online): 2319 – 6718, ISSN (Print): 2319 – 670X
www.ijpsi.org Volume 5 Issue 7 ‖ November 2016 ‖ PP. 22-30
www.ijpsi.org 22 | P a g e
Formulation and evaluation of oral biphasic drug delivery system
of Metronidazole using HPMC polymer
Hani Naseef1,2
, Aseel Samaro2
, Moammal S. Qurt2
, Haneen Nakhleh2
, Noorhan
Kadamani2
, Ramzi Moqadi1
, Mohammed Enaya2
1
Samih Darwazeh Institute of Industrial Pharmacy, Faculty of Pharmacy, Nursing and Health Professions,
Birzeit University, Palestine
2
Doctor of Pharmacy program,Faculty of Pharmacy, Nursing and Health Professions, Birzeit University,
Palestine
Abstract: In the present study, a newly innovative drug delivery system of biphasic Metronidazole (MTZ) tablet
has been studied. An attempt was made to improve the patient’s adherence and the potential clinical outcomes
by reducing the dosing frequency by formulating bilayer tablets containing Metrodinazole. Each bilayer tablet
is composed of a sustained release (SR) layer and an immediate release (IR) layer for rapid drug release. Five
different formulations of bilayer tablets were formulated using HPMC as hydrophilic polymer to retarded the
drug release and the effect of Starch and MCC on the release profile were evaluated. Wet granulation method
was used to prepare granules of the immediate and sustained release layers. The tablets were evaluated for
their physical parameters and all valuesobtained found to be within the acceptable limits. The dissolution test
has been carried out using the USP type II rotating paddle. Collected samples were analyzed using the high
performance liquid chromatography. The mechanisms of Metrodinazole release from the sustained release layer
were fitted into zero-order, first order, Higuchi, Hixon- Crowell model and Korsmeyer-Peppas release model.
The results of the dissolution profiles showed that the drug release from the sustained release layer varied
depending on the amount of HPMC and the presence of Starch or MCC. The kinetics of the release of MTZ
from the different formulations showed good fitting with Higuchi model with correlation coefficients (R2) of
0.9965 - 0.9985. From values obtained for the diffusional exponent, n, Korsmeyer-Peppas equation observed
that for all the formulations n value ranged from 0.4662 to 0.5370, and this demonstrates that the release
mechanism followed non-Fickian type of release ( anomalous transport).
Keywords: Biphasic tablets, HPMC immediate release, infectious diseases, Metronidazole, sustained release.
I. Introduction
Oral drug delivery systems are the most utilized route of administration today; this is due to of the
flexibility in modifying the release pattern of the drug. Tablets among all other orally administered dosage forms
are highly preferred because of their stability, ease of manufacturing and ease of patients’ administration. The
biphasic delivery system is a new innovative drug delivery system utilized to provide immediate and sustained
release doses within the same tablet, thus compliance problems associated with multiple dosing regimens can be
overcome [1].
Diarrheal infections for example, were ranked at the top ten causes of death by the WHO[2].
Metronidazole (MTZ) is an antimicrobial, antiprotozoal medication that is used for multiple infectious diseases
caused by different organisms, including protozoans, Helicobacter pylori, anaerobic bacteria, primarily Gram
negative and Gram positive anaerobes. MTZ has a concentration dependent killing with rapid bactericidal
property and good tissue penetration[3]. It is also well absorbed orally, with relatively short elimination half-
life ranging from 6–8 hours; therefore the use of a sustained release system will be highly beneficial. The
general dosing regimen of MTZ is from 2 to 4 times a-day for 7 to 14 days. It is available as 250, 500 mg
immediate release tablets (IR) and 750 mg extended release tablets (ER) as well. A biphasic tablet of 1000 mg
MTZ is a new novel that is developed to replace multi dosing regimen with once daily. This will improve
patients’ compliance, thus minimizing bacterial resistance as well as improving the clinical efficacy. Moreover,
this biphasic tablet is designed to target specific conditions that use 1000 mg per day, such as: Pelvic
inflammatory disease, bacterial vaginosis, trichomoniasis, Helicobacter pylori infection and others. Biphasic
MTZ tablets are composed of two different layers; the first immediate release layer and the second extended
release layer, in a quickslow release pattern. This system provides an initial burst of drug (Loading dose) with
rapid onset of action. A high Cmax will be achieved rapidly, which will support the mechanism of action of
MTZ, followed by sustained release pattern to maintain plasma drug levels for extended period of time.
HPMC polymer has been used in many studies successfully to sustain the release of different
formulations [4][5][6] Moreover, sustained release matrix tablets of MTZ were successfully prepared using
2. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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HPMC polymer to retard the release of the drug[7]. HPMC retardation of drug release occurs by swelling of the
matrices upon the exposure to the gastric fluids. By time the matrix willerode and or dissolve and release the
drug slowly [8][9]. Starchand Microcrystalline cellulose (Avicel® PH 101) were used to increase the drug
release[10]. Magnesium stearate was used a lubricant andPolyvinylpyrrolidone (PVP) was used as a binder.
The aim of this study was to prepare biphasic MTZ tablets using HPMC polymer. This dosage form is
composed of 250 mg MTZ in the IR layer and 750 mg in the ER layer which will provide an initial loading dose
with rapid onset of action followed by sustained release pattern to maintain a plasma drug levels over a long
period of time.
II. Materials And Methods
1. Materials:
MTZ was obtained as a gift from Jerusalem Pharmaceutical Company. HPMC (10000SH) was gifted from
Pharmacare Phamaceutical Company. Microcrystalline cellulose (Avicel®PH 101), corn starch 1500,
magnesium stearate and polyvinylpyrrolidone (PVP) were gifted from SamihDarwazeh Institute of Industrial
Pharmacy. All reagents used in these experiments were of analytical grades.
2. Preparation of immediate and sustained release layers
The wet granulation method was used to prepare granules of the immediate and sustained release. The
composition of the different formulations is shown in TABLEI. The excipients and the active ingredient
wereblended and granulated with 70% ethanol using granulate stand mixer apparatus. The wet mass was passed
through sieve #18 and the granules were dried at temperature of 40o
C for 2 hours. The dried granules were then
blended with magnesium stearate.
3. Compression of bilayer tablets
The immediate release granules were placed in the die cavity and precompressed . Then the sustained release
granules were placed in the die cavity and allowed for punching with optimum hardness to form bilayer tablets.
Compression was done using 19x8 mm diameter caplet die in a single rotary punch MINIPRESS MII machine.
4. Granules evaluation
4.1 Angle of repose
Angle of repose test was carried out to characterize the flow properties for the IR and the SR granules. The
funnel method was used to determined the angle of repose of granules. A measured quantity of each type of
granules was placed in a funnel. The funnel was fixed in place, 5 cm above the bench surface. The granules
were then allowed to flow through the funnel orifice. The height (h) and the radius (r) of the heap formed were
measured[11]. The test was repeated three times and the angle of repose (Q) was calculated through the
following equation:
Q = tan-1 (h/r) equation.1
4.2 Bulk and Tap Densities
Bulk density (BD) and tap density (TB) were determined using method I outlined in the USP[12].A measured
quantity of each type of granules was added to a graduated cylinder of tapped density apparatus (COPLEY).
After the initial volume was observed, the cylinder was allowed to fall under its own weight onto a hard surface.
The tapping was continued until no further change in volume was noted. BD and TB were calculated using the
following formulas.
BD = Weight of the powder/Volume of the powder (Vbulk) equation.2
TD = Weight of the powder/Minimum volume of the powder (Vtap). equation.3
4.3 Percentage Compressibility (Carr’s index) and Hausner’s Ratio
The percentage compressibility (CI) was calculated from the difference between the TD and BD divided by the
TD and the ratio expressed as a percentage. The Hausner’s ratio (HR) is the ratio between the
TD and BD[11].
CI = [(TD-BD)/TD] ×100 equation.4
HR = TD/BD equation.5
5. Tablets evaluation
The prepared tablets were subjected to various evaluation tests such as weight variation, hardness, friability, and
dissolution test.
3. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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5.1 Weight Variation Test
Weight variation test was done by weighing 20 tablets individually and collectively, calculating the average
weight from the collective weight and comparing the individual tablet weight to the average weight [13].
5.2 Hardness
Hardness was determined using Hardness Tester (Pharmatest PTB 311E ). Ten tablets were randomly selected;
the mean and standard deviation were calculated.
5.3 Friability
Ten pre-weighed tablets were taken randomly and placed into the Three Drum Automated Friability Testing
(Pharmatest PTF 3DR).The machineset to rotate 100 times. Tablets were reweighed after the removal of fines
and the percentage of weight loss was calculated. Friability results below 1% was considered acceptable based
on US [14].
F= (W initial – W final)/ W initial *100%.equation.6
5.4 In Vitro Release study
Six tablets of each formulation of MTZ were taken and tested for dissolution. The USP type II rotating
paddle (SOTAX dissolution tester CLI119) was used to study the drug release from the bilayer tablets. The
dissolution medium consisted of 750 ml 0.1 M HCL for the first two hours, then 250 ml buffer was added to
achieve 1000 ml phosphate buffer pH 6.8 for the next 22 hours according to method A in USP[15]. The
dissolution test was performed at 37 ± 0.5o
C, with a rotation speed of 50 rpm. A sample of 5 ml from the
dissolution medium was withdrawn using SOTAX autosamplar at the interval of 30 min up to 120 min. After
that samples were withdrawn at 3rd
hour followed by 2 hr intervals up to 24 hrs. The sample volume was
replaced by an equal volume of dissolution medium after each withdrawal. Collected samples were analyzed
using the high performance liquid chromatography device (HPLC). MTZ release were determined using a
validated HPLC method. The HPLC analysis was performed using shimadzue HPLC consisting of a pump,
autosampler, column oven, UV detector and LC solution. C8 column was used at a UV detection wavelength of
278 nm. Methanol/water (20:80, v/v), as the mobile phase. Column temperature was maintained at 30°C. Flow
rate and injection volume were 1.0 ml/minand 10 um, respectively.
6. Kinetic Data Analysis
6.1 Mechanism of Drug Release
To explain the mechanisms of MTZ release from sustained release layer of different formulations , the
obtained data of drug release were fitted into zero-order, first order, Higuchi, Hixon- Crowell model and
Korsmeyer-Peppas release model [16-21].
6.2 Zero – order question
To analyze release kinetics, the in vitro release data were plotted as cumulative amount of drug released versus
time. Zero order describes the kinetics where the drug release rate from the tablet is independent from the
concentration of dissolved drug. The release rate data are fitted into the following equation.
Qt=Q0+K0 t equation.7
Where,
Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug in the solution (most times, Q0 = 0)
and
K0 is the zero order release constant expressed in units of concentration/time.
6.3 First order equation
To study the First order release kinetics the release rate data are fitted to the following equation. The data are
expressed as log cumulative percentage of drug remaining versus time. According to First equation order the
drug release rate depends on its concentration.
logC=logC0- Kt/2.303 equation.8
where,
C = The amount of drug un-dissolved at t time,
C0 = Drug concentration at t = 0,
Kt = First order release rate constant.
6.4 Higuchi equation
Higuchi equations assumes that the drug released from the tablet by diffusion mechanism. The data are
expressed as cumulative percentage of drug release versus square root of time which fitted to the following
equation:
Q=k√tequation.9
Where,
4. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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Qt is the amount of drug dissolved in time t,
K0 is Higuchi release constant.
6.5 Hixon- Crowell model
Hixson-Crowell cube root model represents the drug release pattern depending on the change in surface area
and diameter of the particles / tablets. This model is applied for the systems which erode over time. The
following equation where used
Q0
^(1/3)
-Qt
^(1/3)
=k t equation.10
Where,
Qt is the amount of drug release in time t,
Q0 is the initial amount of drug in the tablet
K0 is the rate constant for Higuchi, Hixon- Crowell cube root model
The data are expressed as Cube root of cumulative percentage of drug remaining versus time.
6.6 Korsmeyer-Peppas release model
To elucidate the mechanism of drug release the data were further analyzed using equation proposed
by Korsmeyer and Peppas. The following equation where used
Q/Q0 =k tn
equation.11
where
Q/Q0 = the fraction of drug release at time t
k is the kinetic constant, and n is the diffusion or release exponent which depends on the release mechanism.
When n = 0.45 indicate Fickian diffusion release, when 0.45 < n <0.89 indicate anomalous release kinetics
(coupled diffusion/relaxation), and when 0.89 < n < 1 indicate a zero-order release.
III. Result And Discussion
The granules for both Layers of the different formulations were evaluated for Bulk Density, Tab Density,
Compressibility index, Hausner ratio and Angle of Repose (Table II). The values of precompression parameters
showed that the granules for all formulations have sufficient compressibility and flow properties.
1. Physical Evaluation of tablets
The result of physical evaluation of bi-layer tablets like weight variation, hardness and friability were
represented in Table III. Weight variation of the prepared tablets was found within the limits of pharmacopoeia
[13].One of the main reasons for weight uniformity test is to guarantee appropriate flowability of powders.
Friability test results range between [ 0.2-0.71 %], which met the acceptable limits of less than 1% according to
USP [14], which indicate good mechanical resistance. Hardness ranged between [10-12] newton, which reflects
good mechanical strength.
2. In vitro dissolution
The dissolution profile of different formulations of sustained release MTZ layer and from biphasic
MTZ tablets are shown in Fig.1 and Fig.2 respectively. The dissolution data were analyzed and plotted as the
cumulative percent drug release vs time. Formulations F1, F3, F5, F7 and F9 showed release for 24 hr up to
84.17%, 87.5%, 91.33%, 96.13% and 99.51% respectively(Fig.1). The drug release from the sustained release
layer varied depending on the amount of HPMC and the presence of Starch or MCC. Formulation F1 showed
release less than F3 and F5 due to combination of the hydrophilic polymer(HPMC) in the formulations F3 and
F5 with Starch or MCC respectively. From Fig.1 it was seen that the drug release was higher for Starch and
highest for MCC than the formulations without filler. This release behavior can be attributed to the solubility of
MCC in water which forms pores in the gel layer resulting in more penetration of dissolution medium to the
core of the tablets. On the other hand the use of starch in the tablets retarded the drug release and this
behaviorcausedby two reasons. The first is due to the interaction between Starch and HPMC.This interaction can
affect the properties of the gel layer around the tablets causing to slower penetration of dissolution medium to
the core of the matrix. The second is due to the property of starch to hydrate and form a gel layer barrier due to
intramolecular hydrogen bonds in the highly branched amylopectinwhich affect the gel layer and retard the
drug release[22-23]. Formulations F3 and F5 showed less release than F7 and F9 due to less concentration of
hydrophilic polymer(HPMC) in the formulations F7 and F9. Formulations F2, F4, F6, F8 and F10 showed
release for 24 hr up to 84.51%, 88.11%, 91.2%, 94.1% and 99.5% respectively(Fig.2). For all formulations more
than 40% of MTZ was released within 2 hours of dissolution test. This burst release of MTZ can be due to the
immediate release layer of the formulation. Further release of MTZ was from the sustained release layer for 24
hours.
5. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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3. Kinetics and mechanism of drug release
To explain and evaluate the pattern and mechanism of drug release kinetics the in vitro data obtained
from MTZ dissolution of sustained release layer were fitted to kinetic models, Zero order, first order , Higuchi ,
Hixson-Crowell equations and Korsmeyer-Peppas. The suitability of the model has been judged on the basis
of best fit to the model using the correlation coefficient value (R2). The data obtained from analysis of drug
release kinetics are listed as shown in TABLE (IV). Figure (3) show the results of data analysis according to
Zero order (Fig.3-a ), first order (Fig.3-b ), Higuchi (Fig.3-c ), Hixson-Crowell equations (Fig.3-d ) for
formulation F1.
From the results shown in TABLE (IV), it can be observed that the release kinetics of MTZ from the
different formulations showed good fitting with first order, zero order and Hixson-Crowell with R2 values
0.8453 - 0.9891, 0.9162 - 0.9526 and 0.9728-0.9907 respectively. On the other hand the model with the highest
correlation coefficients (R2) were given by Higuchi with R2 values 0.9965 - 0.9985. Although the results
indicate that the drug is released due to erosion of the gel layer formed around the tablet and simultaneous
diffusion of the drug from this layer. The drug released by diffusion appears to be the main mechanism. These
results can be confirmed by the apparent swelling behavior of the tablets. It was observed during the dissolution
experiments a continuous increase in the thickness of the gel layer formed around the tablets. In addition, the
release profile of MTZ from all formulations displayed good fitting with Hixson-Crowell cube root model of
drug release, implying that erosion might have resulted in the release of MTZ from the tablets . It can be
concluded that the kinetics of this drug release from the tablets can be attributed to erosion and diffusion
mechanism with the diffusion mechanisms maybe the predominant.
To explain the mechanism of MTZ release, the dissolution data were also fitted to exponential
Korsmeyer–Peppas equation and value of release exponent (n) explains the release mechanism of the drug from
the tablets.
The calculated n values are shown in TABLE ( IV ). From values obtained for the diffusional exponent,
n, it can be observed that for all the formulations n value ranged from 0.4662 to 0.5370, and this demonstrates
that the release mechanism followed non-Fickian type of release ( anomalous transport). For all formulations the
n values were less than 0.89 indicating a close to Highuchi release mechanism. Such release pattern could be
attributed to the physical structure of the polymer network and to the strong entanglements HPMC chains which
resisted the gel layer erosion by the dissolution medium [24].
It can also be observed from the results shown in TABLE (IV) that the presence of filler ( Starch 13%
or MCC 16.6 % ) has no significant influence on the kinetics of drug release. The values of n for tablets
without fillers (F1 ) and for tablets with fillers (F3 and F5) were 0.5370, 0.5031 and 0.4763 indicating an
anomalous behavior corresponding to diffusion, erosion and swelling mechanisms. A linear trend of decreasing
n values can be observed from tablets without filler to Starch and to MCC respectively. Tablets containing MCC
exhibited a drug release closer to a diffusion-controlled process compared to Starch and to tablets without filler.
Other research groups have reported similar results that the drug release mechanism was affected by the
presence of filler. They found that the matrices containing lactose exhibited a drug release closer to a diffusion-
controlled process compared to MCC and Starch 1500 [25].
IV. Conclusion
The present study was carried out to design oral bilayer tablet of Metrodinazole containing 250 mg
MTZ in the IR layer and 750 mg MTZ in the ER layer using HPMC 100000SH. The granules of different
formulations have good flow properties and the prepared tablets have good physical characteristics. The Bilayer
tablets showed an initial burst effect to provide the loading dose of the drug, followed by sustained release for
24 h, indicating a promising potential of the Metrodinazole bilayer tablet as an alternative to the immediate
release dosage form.The drug release from the sustained release layer varied depending on the amount of
HPMC and the presence of Starch or MCC. The analysis of the release kinetic data for the different
formulations in this study shows that Higuchi’s model can best describe the kinetics of MTZ conforming to
the diffusion assisted mechanism. Furthermore analysis of release kinetics data using Korsmeyer–Peppas
equation shows that the release mechanism followed non-Fickian type of release ( anomalous transport). It can
beconcluded that the present study indicates that the bilayer tablets of MTZ provides a better option
fordevelopment of a once daily formulation of the drug.
6. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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Table I: Composition of biphasic Metronidazole tablets
Table II: Pre-compression evaluation tests on the prepared granules
Table III: Post-compression evaluation tests on the prepared biphasic MTZ tablets
Table IV: Kinetics data of Metrodinazole release from plots of formulation F-1 , F3, F5, F7, and F9
Formulations Hardness N ±SD
(n 10)
Friability (%)
( n 6 )
Weight (mg) ±SD
(n 10)
Release in 24
hours (%)
F1 10 0.47 820 ± 0.07 84.16%
F2 10.5 0.32 1140 ± 0.08 84.51%
F3 12 0.55 960 ± 0.02 87.5%
F4 10.8 0.65 1260 ± 0.07 91.3%
F5 11.6 0.71 900 ± 0.09 88.1%
F6 12 0.70 1280 ± 0.09 91.2%
F7 10.7 0.20 950 ± 0.01 96.1%
F8 12.2 0.25 1260 ± 0.02 94.1%
F9 10.4 0.30 990 ± 0.06 99.51%
F10 11.9 0.38 1300 ± 0.09 99.5%
7. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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Figure 1: Cumulative MZT released vs. time from different formulations (mean ± SD, n = 6)
Figure 2: Cumulative MZT released vs. time from different formulations (mean ± SD, n = 6)
8. Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC ..
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Figure 3: kinetic evaluation of formulation (F1): a) Zero Order plot, b) First Order plot, c) Higuchi plot, d)
Hixson-Crowell plot.
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