USP Dissolution Test Apparatus Research Articles

Formulation development and evaluation of controlled release matrix tablets of glibenclamide

The present study aimed to formulate and evaluate the controlled-release matrix tablets of Glibenclamide which is an antidiabetic drug that belongs to the second-generation oral hypoglycemics. Matrix tablets were prepared by three different polymers as sustained-release agents, using Glibenclamide as a model drug. Three polymers were selected for this study- HPMC K 15, HPMC K 100, and EC in different drug: polymer ratios. The drug was identified by FTIR spectroscopic method. The pre-compression and post-compression parameters of all formulations were found to be within acceptable limits. The release rate of Glibenclamide from matrix tablets was studied using the USP Dissolution Testing Apparatus type-I (Basket method). The formulation F6 which contained EC 50mg showed a maximum release of 99.28% in 24 hrs and revealed that EC was more effective in sustaining the drug release therefore formulation F6 was selected as the optimized formulation. The in-vitro release data of optimized formulation was fit into various kinetic models, among the different model's data of in-vitro release of best fit into Zero order kinetic model. The formulation best fit the Higuchi model and showed that drug release from the prepared matrix tablets occurs via a diffusion process.

Computational determination of hydrodynamics in the USP dissolution testing Apparatus 1 (rotating basket)

The USP Apparatus 1 is a common analytical tool used to evaluate drug release profiles in pharmaceutical research and development and for formulation-predictive dissolution testing. Different basket mesh sizes can be selected to ensure the most discriminatory method between formulations. In this work the velocity distributions, strain rates, dissipation rates, and flow rates in the rotating basket (10- and 20-mesh) dissolution apparatus operating at 100 rpm in 900-mL liquid fill were predicted using Computational Fluid Dynamics (CFD). The predictions were compared with previous experimental results. In general, substantial agreement between the CFD predictions and the experimental PIV measurements was obtained. The velocity profiles in most regions of the vessel were found to depend on the opening of the basket mesh. The flow rate through the basket was predicted and found to be strongly correlated to the basket mesh size.

Experimental determination and computational prediction of blend time in the USP dissolution testing Apparatus 1

The USP Apparatus 1 (rotating basket) is a preferred testing tool to evaluate the in vitro dissolution performance of pharmaceutical oral solid dosage forms, both as a quality control tool and to determine optimal drug formulations. The test relies on taking samples from the dissolution vessel during the dissolution process to obtain drug dissolution-time profiles. Of significant importance is the determination of the blend time, i.e., the time needed for the drug substance released from the dosage form to become dispersed throughout the vessel, especially at the sampling point. How representative these samples are with respect to the amount of drug dissolved can vary depending on operating and geometrical parameters. Here, the blend time in the USP Apparatus 1 was obtained experimentally and computationally for different operating conditions (basket mesh size, liquid fill volume, and rotation intensity) using the discoloration method coupled with image processing and by conducting time-dependent simulations using the Lattice-Boltzmann Large-Eddy Simulation approach. The experimental and predicted blend times were found to be in agreement. Additionally, an empirical correlation for blend time was developed. These results will help practitioners determine the effect of operating parameters on how representative the samples taken during the test are.

3D Printing and Dissolution Testing of Novel Capsule Shells for Use in Delivering Acetaminophen

Individualized drug delivery improves drug efficacy and safety for patients. To implement individualized drug delivery, patient-specific tailored dosages produced on a small scale are needed. However, current pharmaceutical manufacturing is not suitable for personalized dosage forms. Although convenient to deliver various drugs, current gelatin capsules using animal collagen protein have many limitations, such as releasing drugs too fast and incompatibility with some diets. In contrast, 3D printed capsules have great potential to advance individualized treatments. In this paper, we 3D printed and tested non-animal-based capsule shells for the delivery of acetaminophen. Capsule shells were composed of poly(vinyl) alcohol (PVA) and PVA blends with 5-25% hydroxypropyl methylcellulose (HPMC). Dissolution of acetaminophen when delivered in –hese capsule shells was tested using a USP dissolution test apparatus 2 (paddle type) at gastric pH. The novel shells were compared to each other and to commercially available hard gelatin capsules. Dissolution results show that acetaminophen when delivered in 3D printed capsules was slower than when delivered by gelatin capsules. Increasing the percentage of HPMC in the blend further delayed its release and dissolution. This delay could potentially increase the efficacy and reduce the side effects of acetaminophen. These shells also offer a non-animal-based alternative to gelatin capsules. Furthermore, 3D printing of capsule shells with specific polymer blends may be useful for patient-specific therapy in compounding pharmacies across the country.

Preparation and Investigation of Gastro-Retentive Mucoadhesive Microspheres of Clarithromycin-Resin Complex

Introduction: Helicobacter pylori infection is strongly associated with chronic gastritis and duodenal ulcers which can benefit from gastroretentive delivery of clarithromycin. Objectives: The objective of this study was to investigate mucoadhesive microspheres of the antibiotic – resin complex for gastro-retention, thereby increasing the local effective concentrations of clarithromycin. Methods: Clarithromycin-resin complex granules were coated with the mucoadhesive polymers, Carbopol 934 and Polycarbophil in different ratios of 1:1, 1:2, 1:3 and 1:4 by solvent evaporation method. Prepared microspheres were subjected to characterization for particle size and shape, drug content, in vitro mucoadhesion, in vitro drug release and in vivo gastric residence time in albino rats. Results and Discussion: Particle sizes of the microspheres were found to be in the range of 83 μm-87μm. Scanning electron microscopic images of the formulation showed spherical particles with almost smooth surface morphology for carbopol microspheres. Formulations with both polymers showed mucoadhesion for a period of more than 6 hr. In vitro drug release using the USP dissolution test apparatus appeared to follow first order kinetics. Fluorescence imaging of histo-pathological slides of rats gastric and intestinal mucosa reveal that gastric residence time was found to be longer than 6 h for carbopol microspheres and at least 4 h in the case of polycarbophil microspheres. Conclusion: Carbopol coated microspheres of ion exchange resin complexes of clarithromycin for the gastro-retentive delivery of clarithromycin can be a promising alternative to the conventional oral solid dosage forms in the control of H. pylori induced chronic gastritis or duodenal ulcers.

Formulation and in-vitro evaluation of ciprofloxacin HCL floating matrix tablets

Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage form. Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance and cost-effective manufacturing process. Gastroretentive drug delivery system was developed in pharmacy field and drug retention for a prolonged time has been achieved. The goal of this study was to formulate and in-vitro evaluate Ciprofloxacin HCl controlled release matrix floating tablets. Ciprofloxacin HCl floating matrix tablets were prepared by wet granulation method using two polymers such as HPMC K100M (hydrophilic polymer) and HPMC K15M. All the Evaluation parameters were within the acceptable limits. FTIR spectral analysis showed that there was no interaction between the drug and polymers. In-vitro dissolution study was carried out using USP dissolution test apparatus (paddle type) at 50 rpm. The test was carried out at 37 ± 0.5 0C in 900ml of the 0.1 N HCl buffer as the medium for eight hours. HPMC K100M shows a prolonged release when compared to HPMC K15M. These findings indicated that HPMC K100M can be used to develop novel gastroretentive controlled release drug delivery systems with the double advantage of controlled drug release at GIT pH. On comparing the major criteria in evaluation such as preformulation and in vitro drug release characteristics, the formulation F8 was selected as the best formulation, as it showed the drug content as 99±0.4% and swelling index ratio was 107.14, and in-vitro drug released 61.31±0.65% up to 8 hours. Results indicated that controlled Ciprofloxacin HCl release was directly proportional to the concentration of HPMC K100M and the release of drug followed non-Fickian diffusion. Based on all the above evaluation parameters it was concluded that the formulation batch F8 was found to be best formulation among the formulations F1 to F8 were prepared.

APPLICATION OF NOVEL NATURAL MUCOADHESIVE POLYMER IN THE DEVELOPMENT OF PENTOXIFYLLINE MUCOADHESIVE TABLETS

Objective: The present study was planned to develop a mucoadhesive tablet formulation of the drug pentoxifylline using natural mucoadhesive polymer from the plant Ocimum basilicum Linn.
 Methods: The isolated polymer was used to formulate the mucoadhesive tablets with 3 different concentrations. The tablets were formulated by using direct compression technique and evaluated for various parameters such as thickness, friability, weight variation, hardness, mucoadhesive strength, swelling index by standard methods, and the in vitro drug release studies in USP dissolution test apparatus type-II.
 Results: The swelling index was indirectly proportional to the polymer concentration and the tablets with a high concentration of polymer showed better mucoadhesive strength (28.5532±0.4660). The in vitro drug release showed that the drug release was indirectly proportional to the polymer concentration. The formulation F3 showed the controlled release of drug pentoxifylline (99.84±1.86) for 10 h. The mechanism of drug release was found to be Fickian diffusion and followed the zero-order kinetics, which was proved by its highest linearity (r2) in all the formulations.
 Conclusion: The tablets formulated with the isolated polymer of Ocimum basilicum Linn showed the good mucoadhesive mucoadhesive property and it controlled the release of the pentoxifylline.

Glipizide Loaded Gastro Retentive Floating Tablets: Formulation and in vitro Evaluation

The objective of this research was to formulate and evaluate hydro dynamically balanced controlled drug delivery system of Glipizide. Initially, considering buoyancy as the main criteria, blank tablets were compressed for different formulae with various polymers like Carbopol-940p, HPMC, Citric acid and sodium bi carbonate. The formula selected for design had a combination of Glipizide, Carbopol-940p, HPMC, Citric acid. The tablets were prepared by direct compression method and evaluated for Glipizide content, in vitro release profile and buoyancy. The dissolution study was carried out in simulated gastric fluid using USP dissolution test apparatus employing paddle stirrer. Duration of buoyancy was observed simultaneously when the dissolution has carried out. The Glipizide content of F9 batch 97.87±0.16% and in-vitro release was found to be in the range of 98.85% and from the above result it was concluded F9 was the optimized formulation. This indicates the suitability of the technique chosen for the present dosage form.

Solubility and Dissolution Enhancement of Sulfasalazine by Solid Dispersion Technique

The solubility behavior of drug remains one of the most challenging aspects in formulation development. Most NCE are poorly water soluble, drug not well absorbed after oral administration. Solid dispersion is an increasingly important approach to enhance dissolution rate and solubility of poorly water soluble drug. Sulfasalazine is derivative of mesalazine. Sulfasalazine and its metabolite 5-aminosalicylic acid (5-ASA) are poorly absorbed from gut so its main mode of action is believed to be inside the intestine. It exhibits slow GI absorption rate and inter individual variation of its bioavailability. Thus solubility enhancement and dissolution enhancement of sulfasalazine from its dosage form is an important issue for its in vivo bioavailability and therapeutic efficacy. It was planned to improve the solubility of sulfasalazine by using polymer like Gelucire50/13. Different ratio were employed as 1: 1, 1: 3, 1: 5 and Solid dispersion were prepared by Solvent evaporation method, Physical mixture and Kneading method. Preformulation study was done before going to formulation in that melting point, solubility and compatibility study was done. The prepared solid dispersion also evaluated for percentage yield, percent drug content. Solubility study was done in water. Solid dispersion also characterized by FTIR, DSC, PXRD. In-vitro dissolution study was done in pH6.8 phosphate buffer using USP dissolution test apparatus type II.

Development and Characterization of Atorvastatin Calcium Sustained Release Tablet Using Carbomer-974 and Hypromellose-15000 cps

A new sustained release formulation of Atorvastatin Calcium tablet, exhibiting improved swelling property and compatibility to prolong the drug release was prepared. Sustained release tablets were formulated using varying concentration of Carbomer-974 and Hypromellose-15000 cps, by direct compression method. Physical characteristics, compactibility, swelling index and drug content uniformity of the prepared formulations were determined. The drug release studies was carried out in USP dissolution test apparatus II (paddle) using phosphate buffer of pH 6.8 as dissolution medium for 8 hours and documented the effects of polymers on the drug release profile. The release mechanism was explored and explained with Zero order & Higuchi kinetic models. Formulation F1 and F5 were best fitted in the Higuchi model, representing diffusion mechanism of drug release, while Formulations F2, F3 and F4 showed Zero order model of drug release profile. The drug release pattern, compactibility and swelling index property of the formulated preparations were concentration dependent of the polymers used. Further study is necessary to evaluate the in vitro-in vivo relationship, but this study will be helpful for future to exploit the potential of this drug delivery system for the benefit of the mankind.

Improved Anticancer Activity of Meloxicam Hydrogels in K562 and HL60 Cell Lines

: Objective: The aim of the present study is to prepare poloxamer based formulations of meloxicam to evaluate various parameters like pH stability, drug release and in vitro anticancer activities in cell lines with an intention to formulate injectable sustained biodegradable drug delivery system. Method: Various strengths of meloxicam formulations were prepared by using poloxamer 407. Prepared formulations were analyzed for drug content and pH stability by using HPLC. Drug release studies were tested by using USP dissolution testing apparatus. Further, we evaluated in vitro anticancer activity among these formulations by using sulphorhodamine-B (SRB) assay in two leukemia cell lines such as HL-60 and K-562 cell lines. Results: It showed that among all formulations, F1 formulation showed stability at pH 6.8, 7.0 and 7.4. It also showed 60% drug release and exhibited good anti cancer activity in HL-60 cell line with GI50<10 μg/ml as similar to adriamycin. Conclusion: Comparing these results, we concluded that F1 formulation showed good anticancer activity in cell lines, therefore further studies are necessary to confirm the mechanism of toxicity action studies. Thus these formulations has a potential to be a sustained release, passive targeted deliver system for meloxicam, with reduced side effects associated with the drug.Key words: Meloxicam, Poloxamer 407, Sulphorhodamine-B, Cyclooxygenase, HL-60 and K-562.

Development and Evaluation of Novel Fast Disintegrating Acetaminophen Tablets

In this study, attempts were made to design and developed disintegrating drug delivery system, Acetaminophen fast disintegrating tablet (AFDT) by combining super disintegrants and direct compression method. Acetaminophen is widely used as “over the counter” and “common household drug” as analgesic and antipyretic along with poor absorption due to first pass metabolism. So we aimed to use our novel delivery system to achieve rapid absorption in patients like mentally ill, bed ridden and those who do not have easy access to water. The (AFDT) were produced by combining three super disintegrants viz. Croscarmellose, Crospovidone and Sodium starch glycolate in 4% w/w as ratio of (1:1, 1:2, 2:1) using direct compression method. The optimized batch (A3) of tablet were evaluated for post – compression parameters like hardness (4.5 ± 0.75 kg.cm2), friability ((0.76 %), wetting time (42 ± 0.92 sec), water absorption ratio (98.6 %), disintegration time (24.00 ± 0.83 sec.) were found to be acceptable according to standard limits. The in vitro release rate of acetaminophen from (AFDT) was found to be more than that simple formulation in pH (5.8) using USP dissolution test apparatus type-II. These results indicated that, the new (AFDT) formulation system combined advantage of faster release of acetaminophen, which had better effects of rapid oral absorption. Therefore, the AFDT may be used as fast disintegrating delivery system for OTC drug with poor absorption due to first pass metabolism.

Formulation and Characterization of Ciclopirox Olamine Mucoadhesive Effervescent Tablets for Vaginal Delivery

The study was aimed to design and evaluate a new effervescent mucoadhesive vaginal drug delivery system for ciclopirox olamine (CPO), a broad-spectrum antifungal, antibacterial, and anti-inflammatory agent for effective treatment in vaginal candidiosis. Various polymers like Polyox 303, Carbopol 974P, HPMC K4M, Sodium CMC, HPC, Sodium Alginate, Xanthan Gum, Polycarbophil and Chitosan were used in the formulation of CPO effervescent mucoadhesive vaginal tablet (EMVT) employing direct compression as a method of preparation. The effervescent mixture (citric acid and sodium bicarbonate) was incorporated into the formulations to aid quick wetting and mucoadhesion of tablet followed by drug release modulation. The amount of polymer blends and effervescent mixture was optimized using 32 full factorial design. The swelling, mucoadhesive strength and in-vitro release were studied as dependent responses. The ex-vivo mucoadhesion was determined by modified mucoadhesion assembly. The ex-vivo residence test was carried out by modified USP dissolution test apparatus. In vitro anti-fungal activity of the CPO EMVT was determined in comparison to Candid®-V3 tablet. A good sustained effect and a moderate mucoadhesion (0.31N to 0.67N) were obtained with tablets containing HPMC K4M: Polyox 303 (1:1.4) and effervescent mixture (1:3). Ex-vivo mucoadhesion time of all the formulations was in the range of 8 to 24 h. The effervescent CPO tablet showed significantly higher in-vitro antifungal activity as compare to Candid®-V3 tablet (p&lt; 0.05). The results of short term stability revealed stable characteristics of optimized formulation. The proposed formulation may provide a potential antifungal activity against Candida albicans.&#x0D;

A Novel Approach to Extended Release Clopidogrel: Differentially Coated Mini-Tablets Filled In Hard Gelatin Capsules

The main objective of the present study is to formulate an extended release formulation of clopidogrel bisulphate into mini-tablets coated with a combination of pH dependent polymer, pH independent polymer and pore former. Clopidogrel is extensively absorbed and 50% of drug is eliminated in urine in unchanged form. To improve the bioavailability of clopidogrel, the extended release formulation was formulated with an in-situ solubility enhancer, and barrier coated with moisture protective layer. The barrier coated minitablets are coated with the combination of pH dependant polymer (Hypromellose phthalate HP 50), pH independent polymer (Ethyl cellulose 7cps) and pore former (Hypromellose 5cps) at different ratio, with a weight build up of 10%w/w. In-vitro dissolution was studied in pH 1.2 HCl for 1 hour, followed by pH 6.5 phosphate buffer for 11 hrs, using USP dissolution test apparatus 1 at 100 RPM. The formulation (F37), coated with the ratio of 60:25:15 (Ethocel 7cps: Hypromellose phthalate 50: Hypromellose 5cps), shown the better release of 32% in acid for 1hr, to achieve the loading dose, and the extent of 100% release at 12hr, in pH 6.5 phosphate buffer. Zero-order, first-order, Higuchi, Hixson-Crowell and Korsmeyer peppas models were used to estimate the kinetics of drug release. Drug release kinetics indicated that the drug release was best explained by Higuchi’s equation, as these plots showed the highest linearity (R 2 = 0.9902) indicating the release of drug from matrix as a square root of time dependent process.

Dissolution Profiles of Lanoxin Tablets in Media Supplemented with Soluble and Insoluble Forms of Fiber

Lanoxin (digoxin) is available as 125 µg or 250 µg tablets for oral administration used to treat heart failure and arrhythmias. The objective of this study was to develop and investigate a comparativedissolutionstudy performed on lanoxin tablets in presence of insoluble or soluble forms of fiber. This study was performed to understand possible influence of fiber (psyillium husk, wheat dextrin, or powdered cellulose)on dissolutionof lanoxin in physiological relevant temperature and pH.Dissolutiontesting was performed using a USP dissolution testing apparatus II paddlerotating at 100 r/min, in 600 mL simulated gastric fluid (pH 1.2) which was maintained at (37 +/- 0.5 °C). A floating cellulose dialysis tube was used to collect sampling fractions. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Results indicate that the presence of psyillium husk in the dissolution medium hindered digoxin release. Statistical results reveal that the release profiles of digoxin in presence of wheat dextrin or powdered cellulose did not influence drug release.

Velocity profiles and shear strain rate variability in the USP Dissolution Testing Apparatus 2 at different impeller agitation speeds

The fluid velocity profiles at different locations inside a standard USP Dissolution Testing Apparatus 2 were experimentally obtained via Laser Doppler Velocimetry (LDV) at three impeller agitations speeds, namely 50rpm, 75rpm and 100rpm. The experimental results were compared with the predictions obtained with Computational Fluid Dynamics (CFD) where the κ–ω model with low Reynolds number correction was used to account for turbulence effects. In general, good agreement was found between the experimental LDV velocity measurements and the CFD simulation predictions. The non-dimensional tangential, axial and radial velocity profiles (scaled with the impeller tip speed) and the flow pattern were found to be nearly independent of the agitation speed in most regions of the vessel, implying that increasing the agitation speed generally produced a corresponding increase in the local values of the velocity. However, the velocity profiles and flow pattern in the inner core region just below the impeller, where the dissolving tablet is usually located, were found to be much less sensitive to agitation speed. In this region, the axial and radial velocities were especially low and were not significantly affected by agitation increases. This inner core region at the center of the vessel bottom persisted irrespective of agitation intensity. The CFD predictions also indicated that increasing the agitation speed resulted in a higher shear strain rate distribution along the vessel bottom, although the strain rate was always very low at the center of the vessel bottom, even when the agitation speed was increased.

Controlled release of carbamazepine from carboxymethyl chitosan-grafted- 2-hydroxyethylmethacrylate matrix tablets

The aim of the study was to prepare the con- trolled release dosage of carbamazepine matrix tablets using wet granulation technique. The graft copolymerization of carboxymethyl chitosan (CMCH) with 2-hydroxyethylme- thacrylate (HEMA) was carried out. The product was char- acterized by Fourier-transform infrared, scanning electron microscopy, transmission electron micrograph, and X-ray diffraction anayses. CMCH-g-HEMA was used as binder to prepare the matrix tablets containing carbamazepine. The properties of tablets like hardness, friability, and dissolution influenced by binder were studied. In vitro release of the matrix tablets was carried out with the phosphate-buffered solution (pH 7.4) at 37 � C and 100 � g using USP dissolution test apparatus. Release rate of carbamazepine from con- trolled release matrix tablets was compared with the com- mercially marketed tablet, Tagretol 200. Results show that after 6 hrs percentage drug release of formulated tablet CGH5 was 20.42% and that of Tegretol 200 was 18.32%. V C 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115: 3442-3450, 2010

Hydrodynamic, mass transfer, and dissolution effects induced by tablet location during dissolution testing

Tablets undergoing dissolution in the USP Dissolution Testing Apparatus II are often found at locations on the vessel bottom that are off-center with respect to the dissolution vessel and impeller. A previously validated CFD approach and a novel experimental method were used here to examine the effect of tablet location on strain rates and dissolution rates. Dissolution tests were conducted with non‐disintegrating tablets (salicylic acid) and disintegrating tablets (Prednisone) immobilized at different locations along the vessel bottom. CFD was used to predict the velocity profiles and strain rates when the tablets were placed at such locations. A CFD‐based model was derived to predict the mass transfer coefficient and dissolution curves, which were then compared to the experimental results. Both non‐disintegrating and disintegrating off‐center tablets experimentally produced higher dissolution rates than centered tablets. The CFD‐predicted strain rate distribution along the bottom was highly not uniform and the predicted strain rates correlated well with the experimental mass transfer coefficients. The proposed CFD‐based model predicts mass transfer rates that correlate well with the experimental ones. The exact tablet location has a significant impact on the dissolution profile. The proposed model can satisfactorily predict the mass transfer coefficients and dissolution profiles for non‐disintegrating tablets. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1511–1531, 2009

In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors

Hyaluronic acid (HA) coupled chitosan nanoparticles (HACTNP) bearing 5-flurouracil (5FU) were prepared, by ionotropic gelation method, for the effective delivery of drug to the colon tumors. HACTNP appeared to be spherical in shape and mean size was found to be around 150 ± 3.4 nm with low polydispersity index. The in vitro drug release was investigated using USP dissolution test (paddle type) apparatus in different simulated GIT fluids. The biocompatibility of NPs formulations were evaluated for in vitro cytotoxicity by MTT assay using HT-29 cell lines and cell uptake was assessed by fluorescent microscopy. Cellular uptake of HACTNP was determined by incorporating calcein as a fluorescent marker. The cellular uptake of fluorescent HACTNP was clearly evidenced by fluorescence microscopy. HACTNP nanoparticles showed significant higher uptake by cancer cells as compared to uncoupled nanoparticles and the uptake of HA coupled CTNPs by HT-29 colon cancer cells were observed to be 7.9 times more as compared to uncoupled CTNPs at the end of 4 h. The cytotoxicity of 5FU incorporated in HACTNP was higher compared to the conventional 5FU solution, even at the lower concentrations. 5FU in HACTNP was about 2.60-folds more effective than free 5FU on HT-29 cells.

Dissolution test for site-specific release isoniazid pellets in USP apparatus 3 (reciprocating cylinder): Optimization using response surface methodology

The present work aims to predict drug release from novel site-specific release isoniazid pellets, in USP dissolution test apparatus 3, using the response surface methodology (RSM). Site-specific release isoniazid pellets were prepared by extrusion-spheronization followed by aqueous coating of Acryl-EZE ®. RSM was employed for designing of the experiment, generation of mathematical models and optimization study. A 3 2 full factorial design was used to study the effect of two factors (at three levels), namely volume of dissolution medium (150, 200, 250 ml) and reciprocation rate (5, 15, 25 dips per min). Amount of drug released in 0.1 N hydrochloric acid at 2 h and in pH 6.8 phosphate buffer at 45 min were selected as responses. Results revealed that both, the volume of medium and reciprocation rate, are significant factors affecting isoniazid release. A second order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized conditions resulted in dissolution data that were close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimization of dissolution test conditions for site-specific release isoniazid pellets.