In vitro conditions for the study of the in vivo performance of sustained-release theophylline matrix tablets administered in fasted conditions and with a high-fat diet

Dissolution profiles of theophylline (TP) from three types of sustained-release (SR) matrix tablets (plastic [PL], lipid [LP], and hydrophilic [HP]) in different dissolution media, with and without enzymes, were established. Also investigated was the influence of a treatment of the tablets with peanut oil prior to the dissolution test. The in vivo behavior of the tablets under the fasted state and with the concomitant administration with a high-fat diet was previously evaluated; the diet produced changes in the absorption profiles for the three matrix tablets in comparison with fasted administration. Level A correlations were obtained between cumulative percentage dissolved (CPD) and cumulative percentage absorbed (CPA). For the fasted condition, better correlations were obtained with water as the dissolution medium for the HP and LP matrix; for PL matrix, the best correlation was obtained with a medium with gradual change of pH. The pretreatment with peanut oil showed better correlations for the fed state.     

Spray-dried high-amylose sodium carboxymethyl starch: impact of α-amylase on drug-release profile

Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0?IU/L to 20000?IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f_2?>_?50) for all but only one of the studied conditions (f_2?=_?47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1?h or 3?h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected.     

Excipient-excipient interaction in the design of sustained-release theophylline tablets: in vitro and in vivo evaluation

Sustained-release (SR) theophylline (TPH) tablets were prepared by applying the moisture-activated dry granulation method. The interaction between the excipients sodium alginate (SAL) and calcium gluconate (CG) was the base for the formation of a cross-linked matrix that may regulate TPH release from the formulated tablets. The prepared granules showed good physical characteristics concerning the flow properties and compressibility, with the angles of repose in the range 29-31, and the compressibility indices ranged between 15% and 25%. The granules had low friability values (3.0%-4.2%), depending on SAL:CG ratios. The corresponding tablets showed good physical properties, with a lower rate of drug release compared with the commercial TPH tablets (Quibron®). The release of TPH from the prepared tablets was not markedly affected by either the concentration of added dry binder (carbopol 934) or the tablet hardness, indicating that the rate-determining step in drug release was the diffusion through the produced calcium alginate matrix. Tablets formulated with equal ratios of CG and SAL that showed good physical properties and slow TPH release were chosen for bioavailability studies in beagle dogs, and results were compared with those for Quibron. The in vivo data showed a comparable plasma concentration profile for both tablet formulations, with prolonged appearance of drug in the plasma in detectable amounts for up to 24 h. The formulated tablets showed 104.65% bioavailability relative to that of the commercial tablets. The rate and extent of absorption of TPH showed no significant differences from that of the commercial tablets. Moreover, no significant differences were found in the pharmacokinetic parameters related to the rate and extent of TPH absorption from the prepared and commercial tablets.     

A new rapidly absorbed paracetamol tablet containing sodium bicarbonate. I. A four-way crossover study to compare the concentration-time profile of paracetamol from the new paracetamol/sodium bicarbonate tablet and a conventional paracetamol tablet in fed and fasted volunteers

The primary objective of this four-way crossover study was to compare the concentration-time profile of paracetamol from a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with a conventional paracetamol tablet (P), in a panel of 28 fed and fasted healthy volunteers. The results demonstrated that paracetamol was absorbed more rapidly from tablets containing sodium bicarbonate compared to conventional tablets, as indicated by a shorter tmax in both the fed and fasted state and a higher Cmax in the fasted state. The two formulations were bioequivalent with respect to area under curve (AUC). Food did not affect the extent of absorption from either formulation, as indicated by AUC, however, food did reduce the rate of absorption from both formulations, as indicated by a longer tmax and a lower Cmax. Metabolic activation of paracetamol to its oxidation metabolites, as assessed by combined partial clearances to subsequent secondary metabolites cysteine and mercapturic acid conjugates, indicated that the two formulations were bioequivalent in this respect.     

Excipient-Excipient Interaction in the Design of Sustained-Release Theophylline Tablets: In Vitro and In Vivo Evaluation

Sustained-release (SR) theophylline (TPH) tablets were prepared by applying the moisture-activated dry granulation method. The interaction between the excipients sodium alginate (SAL) and calcium gluconate (CG) was the base for the formation of a cross-linked matrix that may regulate TPH release from the formulated tablets. The prepared granules showed good physical characteristics concerning the flow properties and compressibility, with the angles of repose in the range 29–31, and the compressibility indices ranged between 15% and 25%. The granules had low friability values (3.0%–4.2%), depending on SAL:CG ratios. The corresponding tablets showed good physical properties, with a lower rate of drug release compared with the commercial TPH tablets (Quibron®). The release of TPH from the prepared tablets was not markedly affected by either the concentration of added dry binder (carbopol 934) or the tablet hardness, indicating that the rate-determining step in drug release was the diffusion through the produced calcium alginate matrix. Tablets formulated with equal ratios of CG and SAL that showed good physical properties and slow TPH release were chosen for bioavailability studies in beagle dogs, and results were compared with those for Quibron. The in vivo data showed a comparable plasma concentration profile for both tablet formulations, with prolonged appearance of drug in the plasma in detectable amounts for up to 24 h. The formulated tablets showed 104.65% bioavailability relative to that of the commercial tablets. The rate and extent of absorption of TPH showed no significant differences from that of the commercial tablets. Moreover, no significant differences were found in the pharmacokinetic parameters related to the rate and extent of TPH absorption from the prepared and commercial tablets.     

Swelling,erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets

Background: Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Method: Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. Results: The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. Conclusion: The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.     

Peroral Sustained-Release Film-Coated Pellets as a Means to Overcome Physicochemical and Biological Drug-Related Problems. I. In Vitro Development and Evaluation

Abstract

In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.     

Effect of Processing on Release from an Inert, Heterogeneous Matrix

Matrixes containing 40% ephedrine hydrochloride and hydrogenated castor oil are prepared by two processes: (a) compression of a physical mixture and (b) compression of a congealed melt. The release from the melt matrix is slower than from the matrix prepared by compression of a physical mixture. applied pressure on the release profile is studied. For matrixes prepared by both processes as the applied pressure is increased, the release rate is slower; however, this effect is more pronounced for the physical mixture matrix. The effect of comminution of the medicinal compound on release profile is considered. mixture the fastest release occurs from the finer particles suggesting a boundary layer diffusion. In matrixes produced by the melt process as the particle size is decreased, the release is slowed presumably because of an increased tortuosity and more intimate contact between the ephedrine hydrochloride and the hydrogenated castor oil, which produces mass transfer by matrix diffusion.     

Effect of Processing on Release from an Inert,Heterogeneous Matrix

Abstract

Matrixes containing 40% ephedrine hydrochloride and hydrogenated castor oil are prepared by two processes: (a) compression of a physical mixture and (b) compression of a congealed melt. The release from the melt matrix is slower than from the matrix prepared by compression of a physical mixture. applied pressure on the release profile is studied. For matrixes prepared by both processes as the applied pressure is increased, the release rate is slower; however, this effect is more pronounced for the physical mixture matrix. The effect of comminution of the medicinal compound on release profile is considered. mixture the fastest release occurs from the finer particles suggesting a boundary layer diffusion. In matrixes produced by the melt process as the particle size is decreased, the release is slowed presumably because of an increased tortuosity and more intimate contact between the ephedrine hydrochloride and the hydrogenated castor oil, which produces mass transfer by matrix diffusion.     

Formulation and Release Kinetics of Sustained Release Phenylpropanolamine Hydrochloride Granules and Tablets

Abstract

Sustained release phenylpropanolamine hydrochloride (PPH) granules and tablets were prepared using HPMC, HPMC and SCMC, Eudragit RS, Eudragit RS+L or HPMC + Eudragit RS matrices. The release pattern of PPH from the prepared granules and tablets was found to be in the following order HPMC > HPMC + SCMC > RS > RS + 1> HPMC + RS. The results revealed that, although the drug concentration was kept constant in all the prepared granules and tablets, the drug release from these formulations was clearly different and depends mainly on the type of matrix used. The presence of Eudragit L with Eudragit RS and Eudragit RS with HPMC resulted in a marked decrease in the drug release compared with that obtained from the matrix containing HPMC or Eudragit RS alone. The release data of PPH from the prepared granules and tablets were treated mathematically according to zero order, first order, Langenbuchar, modified Langenbucher and Higuchi models. The results revealed that no one model was able adequately to describe the drug release profiles from these formulations. In-vivo studies in human volunteers showed that, the peak urinary excretion of PPH occurred over a sustained period from 2 to 6.5 hr in case of HPMC + SCMC tablets and from 2 to 10 hr in case of either RS+L or HPMC + RS tablets.     

Modulation of drug (metoprolol succinate) release by inclusion of hydrophobic polymer in hydrophilic matrix

The objective of this study was to develop sustained release (SR) matrix tablets of metoprolol succinate (MS), by using different polymer combinations and fillers, to optimize by response surface methodology and to evaluate biopharmaceutical parameters of the optimized product. Matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC); and lactose and dibasic calcium phosphate dihydrate (DCP) as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was subjected to further study like scanning electron microscopy, swelling study and in vivo study in rabbit model. Both in vitro and in vivo study revealed that combining of HPMC K100M (21.95%) with EC (8.85%), and use of DCP as filler sustained the action up to 12 h. The in vivo study of new SR tablets showed significant improvement in the oral bioavailability of MS in rabbits after a single oral dose of 25 mg. The delayed T(max) and lower C(max) indicated a slow and SR of MS from the optimized matrix tablets in comparison with the immediate release dosage form. The developed SR (MS) tablet of improved efficacy can perform therapeutically better than conventional tablet.     

The Effect of Polymer Coating Systems on the Preparation, Tableting, and Dissolution Properties of Sustained-Release Drug Pellets

The preparation of sustained-release (SR) drug pellets and their tablets was evaluated. Pellets containing indomethacin, pseudoephedrine hydrochloride (P-HCl), or pseudoephedrine (P) base were prepared by spraying a mixture of drug, Eudragit S-100 resins, dibutyl sebacate, and alcohol onto nonpareil seeds via the Wurster-column process. The oven-dried drug/Eudragit S-100 (DS) pellets were coated with different levels of Eudragit RS and Eudragit S-100 acrylic resins. Tablets containing P-HCl or P-base SR pellets, microcrystalline cellulose, and Methocel K4M were compressed. The solubility of the drug entity in the polymer solution was found to be the most critical factor affecting the yield and the physical properties of the resultant DS pellets. Dissolution studies of Eudragit RS coated drug pellets demonstrated that the release profiles depended not only on the physicochemical properties of the drug, particularly aqueous solubility, but also on the coating levels. The release rate profiles of the matrix tablets can be modified by varying the types of P-HCl or P-base SR pellets in the formulation. The release of drug from the matrix tablets is primarily matrix controlled.     

Release of a Low Dose Water Soluble Medicinal Agent from Inert Wax Matrix Tablets

Directly compressible wax matrix tablets have been developed for a low dose medicinal agent (Chloropheniramine maleate). A mixture of castor wax NF and Hydrogenated Vegetable Oil NF, was optimized in the ratio of 50:50 as matrix based on their bulk density and particle size distribution and compression properties The compression properties indicated that the increase in compression forces resulted in a tablet of higher hardness up to 8 Kp. However further increase in compression forces resulted in the decrease in hardness and capping was apparent.

The result of dissolution studies indicated no significant effect of hardness and tablet shape (Round and rectangular shaped) on the dissolution properties of wax matrix tablets. A plot of percent drug released various square root of time exhibited a linear relationship. The release rates of CPM from wax matrix tablets were found to be independent of the rotational speed of paddles between 50-75 RPM. From these results, the release mechanism of CPM from wax matrix tablets appears to be primarily diffusion controlled rather than matrix erosion.     

Studies Comparing Kollicoat MAE 30 D with Commercial Cellulose Derivatives for Enteric Coating on Caffeine Cores

Abstract

The products that are processed in aqueous form, such as Aqoat MF (suspension), Aquateric (pseudolatex), HP 55 (ammonia-based solution), and Kollicoat MAE 30 D (latex), were compared (in the form of spray dispersions, isolated films prepared from the dispersions, and caffeine-film-coated tablets with 5.5, 8.0, and 11.0 mg film/cm²) with one another and with ethanolic HP 55 S solution. The addition of pigments to all of the liquid preparations, with the exception of the ammoniacal solution of HP 55, led to a slight increase in pH. In each case, the viscosity of both solutions was well above that of the other formulations. The minimum film-forming temperature was decidedly reduced by the addition of pigment. Kollicoat MAE was the undissolved film-former that had the smallest particle size and particle size distribution. The next smallest were those of Aqoat MF. The latex and the suspension were the only products that were sensitive to shear and heat. The isolated films did not display any tack. The strongest films and the films most impermeable to water vapor were obtained from solutions, and this can be ascribed to the fine distribution of the film-former. None of the isolated films showed signs of dissolving at pH 4.5. At pH 5.5, only the HP 55 was dissolved. This was because HP 55 was processed in ammonia-based solution; as a result of which, films that were not very resistant to gastric juice were obtained. The other formulations did not dissolve until the pH reached 6.0. As the pH rose, the rate of dissolution increased for all of the films. The permeability to protons was similar to that of caffeine-film-coated tablets to gastric juice. The resistance increased in the following sequence: HP 55 (ammonia-based) < Aquateric < Aqoat MF < HP 55 S (organic) and Kollicoat MAE.     

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.     

Release of a Low Dose Water Soluble Medicinal Agent from Inert Wax Matrix Tablets

Abstract

Directly compressible wax matrix tablets have been developed for a low dose medicinal agent (Chloropheniramine maleate). A mixture of castor wax NF and Hydrogenated Vegetable Oil NF, was optimized in the ratio of 50:50 as matrix based on their bulk density and particle size distribution and compression properties The compression properties indicated that the increase in compression forces resulted in a tablet of higher hardness up to 8 Kp. However further increase in compression forces resulted in the decrease in hardness and capping was apparent.

The result of dissolution studies indicated no significant effect of hardness and tablet shape (Round and rectangular shaped) on the dissolution properties of wax matrix tablets. A plot of percent drug released various square root of time exhibited a linear relationship. The release rates of CPM from wax matrix tablets were found to be independent of the rotational speed of paddles between 50–75 RPM. From these results, the release mechanism of CPM from wax matrix tablets appears to be primarily diffusion controlled rather than matrix erosion.     

Semisolid matrix filled capsules: an approach to improve dissolution stability of phenytoin sodium formulation

Seven semisolid fill bases were selected for the formulation of 24 capsule formulations, each containing 100 mg of phenytoin sodium. The fill materials were selected based on the water absorption capacity of their mixtures with phenytoin sodium. The fill matrices included lipophilic bases (castor oil, soya oil, and Gelucire (G) 33/01), amphiphilic bases (G 44/14 and Suppocire BP), and water-soluble bases (PEG 4000 and PEG 6000). The drug:base ratio was 1:2. Excipients such as lecithin, docusate sodium, and poloxamer 188 were added to some formulations. The dissolution rate study indicated that formulations containing lipophilic and amphiphilic bases showed the best release profiles. These are F4 (castor oil-1% docusate sodium); F10 (castor oil-3% poloxamer 188); F14 (G33/01-10% lecithin); F17 (G33/01-1% docusate sodium), and F20 (Suppocire BP). Further, the dissolution stability of the five formulations above was assessed by an accelerated stability study at 30°C and 75% RH using standard Epanutin capsules for comparison. The study included the test and standard capsules either packed in the container of marketed Epanutin capsules (packed) or removed from their outer pack (unpacked). Release data indicated superior release rates of castor oil based formulations (F4 and F10) relative to standard capsules in both the unpacked and packed forms. For instance, the extent of drug release at 30 min after 1 month was 91% for F4 and F10 and 20% for standard capsules. Drug release from packed capsules after 6 months storage was 88% for both formulations F4 and F10 and 35% for standard capsules. In conclusion, the pharmaceutical quality of phenytoin sodium capsules can be improved by using a semisolid lipophilic matrix filled in hard gelatin capsules.     

Studies on Sustained release XI: Lipid Granules of Sulfamethizole

The aim of this study was to prepare a sustained release granule of sulfamethizole, employing hydrogenated castor oil (Cutina HR). After the dosage form design was made, different formulations were prepared as granules by the fusing technique. The granules manufactured were analysed with sieves between 0.5 and 1 mm openings. The fractions obtained were tested for dissolution rate for a period of seven hours with fluids of varying pHs with the continuous flow-through cell apparatus.

Upon the kinetic evaluation of dissolution data, it was seen that the target release rates were achieved. The results showed that, the drug release rates increase with increasing amounts of PEG 4000 added to the formulations; up to a certain percentage. No increase beyond this point was noticed.

The drug release rates mostly followed zero-order and modified Hixson-Crowell kinetics.     

Temperature/Humidity sensitivity of sustained-release formulations containing Kollidon SR

The effects of temperature and humidity on tablets containing Kollidon® SR have been evaluated using diphenhydramine HCl as a model drug. Exposure of tablets to ICH accelerated stability condition (40°C/75%RH) in an open dish resulted in rapid increases in tablet hardness, accompanied by step-wise decreases in dissolution rate. Such a change can be observed as fast as an hour upon exposure. The tablet matrix appears to rapidly absorb atmospheric moisture, as demonstrated by tablet weight gain and moisture adsorption isotherms. Exposure to 25°C/60%RH similarly resulted in increases in tablet hardness, although with minimal impact on dissolution. Potential implications of such rapid moisture uptake during aqueous film-coating were further evaluated by spraying either water or an Opadry solution in a coating pan. Exposure of Kollidon SR tablets to the aqueous coating process indeed resulted in noticeable changes in both hardness and dissolution. Application of the Opadry solution appears to affect tablet behavior to a lesser degree, compared to water, most likely due to protection via formed barrier film. Attention needs to be paid to the extreme sensitivity of Kollidon SR matrix tablets to temperature and moisture during product development.     

Development of Polysaccharide-Based Colon Targeted Drug Delivery Systems for the Treatment of Amoebiasis

ABSTRACT

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, β-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30–40% drug release during the initial 4–5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18–24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.