Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm⁻¹. XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07°C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 μm. Storage of the microspheres at 40°C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.     

Formulation development and in-vitro/in-vivo correlation for a novel sterculia gum-based oral colon-targeted drug delivery system of azathioprine

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6?h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T_max, prolonged absorption time, decreased C_max and absorption rate constant (K_a) indicating reduced systemic toxicity of the drug as compared to other dosage forms.     

Eudragit S100 coated microsponges for Colon targeting of prednisolone

Context: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease.

Objective: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery.

Materials and methods: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72?kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release.

Results: PLMs were found to be nano-porous spherical microstructures with size around 35?µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1?hr in SGF (pH 1.2), 2 to 3?h in SIF (pH 4.6), 4–5?h in SIF (pH 6.8), and 6–24?h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24?h.

Discussion and conclusion: In vitro drug release studies revealed that drug starts releasing after 5?h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.     

Resistant starch as a carrier for oral colon-targeting drug matrix system

In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl₃, and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.     

Effect of heat on characteristics of chitosan film coated on theophylline tablets

The effect of heat on the characteristics of chitosan film coated on theophylline tablets was studied. Chitosan of high viscosity grade with molecular weight in the range of 800,000-1,000,000, 80-85% degree of deacetylation was used as a film former by dissolving in 1% v/v acetic acid solution. The coated tablets had been cured at 40, 60, and 100°C for 6, 12, and 24 hr. The morphology of the film at the edge and surface of coated tablets was investigated using scanning electron microscopy. Film cracking was increased and clearly observed in the coated tablets cured at 100°C for 24 hr. As a result, more water could be absorbed into the tablets, followed by faster disintegration and faster drug release. The evidence of partial conversion of chitosonium acetate to chitin in the ¹³C nuclear magnetic resonance (NMR) spectra of chitosan films cured at 40, 60, and 100°C was observed, but it had no effect on drug release behavior. Theophylline tablets coated with chitosan films gave sustained release behavior in various media, i.e., distilled water, 0.1 N hydrochloric acid, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. In addition, the film coating temperature at 55-60°C and curing process at 40 and 60°C had no effect on the drug release from theophylline tablets coated with chitosan polymer. Finally, it might be concluded that both the physical and chemical properties of chitosan films were affected by heat.     

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.     

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.     

In vitro evaluation of compression-coated glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu2+)-loaded microparticles for colonic drug delivery

Glycyl-L-histidyl-L-lysine-Cu(II) (GHK-Cu(2+))-loaded Zn-pectinate microparticles in the form of hydroxypropyl cellulose (HPC) compression-coated tablets were prepared and their in vitro behavior tested. GHK-Cu(2+) delivery to colon can be useful for the inhibition of matrix metalloproteinase, with the increasing secretion of tissue inhibitors of metalloproteinases (TIMPS),which are the major factors contributing in mucosal ulceration and inflammation in inflammatory bowel disease. The concentration of peptide was determined spectrophotometrically. The results obtained implied that surfactant ratio had a significant effect on percent production yield (1.25 to 1.75 w/w; 72.22% to 80.84%), but cross-linking agent concentration had not. The entrapment efficiency (EE) was found to be in the range of 58.25-78.37%. The drug-loading factor significantly increased the EE; however, enhancement of cross-linking agent concentration decreased it. The release of GHK-Cu(2+) from Zn-pectinate microparticles (F1-F8) in simulated intestinal fluid was strongly affected by cross-linking agent concentration and drug amount (50 mg for F1-F6; 250 mg for F7-F8), but not particularly affected by surfactant amount. Release profiles represented that the microparticles released 50-80% their drug load within 4 h. Therefore, the optimum microparticle formulation (F8) coated with a relatively hydrophobic polymer HPC to get a suitable colonic delivery system. The optimum colonic delivery tablets prepared with 700 mg HPC-SL provided the expected delayed release with a lag time of 6 h. The effects of polymer viscosity and coat weight on GHK-Cu(2+) release were found to be crucial for the optimum delay of lag time. The invention was found to be promising for colonic delivery.     

Pharmaceutical Applications of Shellac: Moisture-Protective and Taste-Masking Coatings and Extended-Release Matrix Tablets

Abstract

Shellac is a natural polymer, which is used as enteric coating material in pharmaceutical applications. The major objective of the present study was to investigate the potential of shellac for other purposes, namely to provide moisture-protective and taste-masking coatings as well as extended-release matrix tablets. The efficiency of shellac to achieve moisture protection and taste masking was compared with that of hydroxypropyl methylcellulose (HPMC), which is most frequently used for these purposes. Shellac-coated tablets showed lower water uptake rates than HPMC-coated systems at the same coating level. The stability of acetylsalicylic acid was higher in tablets coated with shellac compared with HPMC-coated systems, irrespective of the storage humidity. Therefore, lower shellac coating levels were required to achieve the same degree of drug protection. Shellac coatings effectively masked the unpleasant taste of acetaminophen tablets. Compared to HPMC, again lower coating levels were required to achieve similar effects. The resulting drug release in simulated gastric fluid was not significantly altered by the thin shellac coatings, which rapidly ruptured due to the swelling of the coated tablet core. In addition, shellac was found to be a suitable matrix former for extended-release tablets. The latter could be prepared by direct compression or via wet granulation using ethanolic or ammoniated aqueous shellac binder solutions. The resulting drug-release patterns could effectively be altered by varying different formulation and processing parameters.     

Pharmaceutical applications of shellac: moisture-protective and taste-masking coatings and extended-release matrix tablets

Shellac is a natural polymer, which is used as enteric coating material in pharmaceutical applications. The major objective of the present study was to investigate the potential of shellac for other purposes, namely to provide moisture-protective and taste-masking coatings as well as extended-release matrix tablets. The efficiency of shellac to achieve moisture protection and taste masking was compared with that of hydroxypropyl methylcellulose (HPMC), which is most frequently used for these purposes. Shellac-coated tablets showed lower water uptake rates than HPMC-coated systems at the same coating level. The stability of acetylsalicylic acid was higher in tablets coated with shellac compared with HPMC-coated systems, irrespective of the storage humidity. Therefore, lower shellac coating levels were required to achieve the same degree of drug protection. Shellac coatings effectively masked the unpleasant taste of acetaminophen tablets. Compared to HPMC, again lower coating levels were required to achieve similar effects. The resulting drug release in simulated gastric fluid was not significantly altered by the thin shellac coatings, which rapidly ruptured due to the swelling of the coated tablet core. In addition, shellac was found to be a suitable matrix former for extended-release tablets. The latter could be prepared by direct compression or via wet granulation using ethanolic or ammoniated aqueous shellac binder solutions. The resulting drug-release patterns could effectively be altered by varying different formulation and processing parameters.     

磁性壳聚糖-5-氟尿嘧啶纳米粒的制备及体外释药性能

采用交联-聚合法在超声波的作用下,制备了磁性壳聚糖-5-氟尿嘧啶纳米粒(M CN-Fu)。透射电子显微镜(TEM)和红外光谱(IR)等分析结果表明,M CN-Fu粒子外形规整,分散性好,粒径主要在50 nm~60 nm之间。紫外-可见光谱分析结果表明,M CN-Fu的载药量为21.3%,在磷酸盐缓冲溶液(pH=7.2)中,30 h的累积释药率为67.6%,具有良好缓释性能,并具有良好磁响应性能。     

Effect of Simulated Gastrointestinal Conditions on Drug Release from Pectin/Ethylcellulose as Film Coating for Drug Delivery to the Colon

The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat.     

Effect of simulated gastrointestinal conditions on drug release from pectin/ethylcellulose as film coating for drug delivery to the colon

The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat.     

Effect of Simulated Gastrointestinal Conditions on Drug Release from Pectin/Ethylcellulose as Film Coating for Drug Delivery to the Colon

The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat.     

Hydration,Erosion, and Release Behavior of Guar-Based Hydrophilic Matrix Tablets Containing Total Alkaloids of Sophora alopecuroides

It is a challenge to deliver water-soluble drug based on hydrophilic matrix to colon because of swelling and erosion of polysaccharides in contact with media. In our study, guar-based hydrophilic matrix tablets containing water-soluble total alkaloids of Sophora alopecuroides prepared by wet granulation technique were evaluated. A novel method was established to investigate the changes of swelling and volume for guar-based tablets in undynamic state, which generally showed a rapid swelling and volume change in the first 9 h, then the hydrated speed slowed down. On the other hand, the influence of different pH of the media on water uptake and erosion of various guar-based formulations in dynamic state indicated that the hydrated constants in simulated gastric fluid (SGF) was higher than that in SIF, which followed varied mechanism of water penetration by fitting Davidson and Peppas model. The extent of erosion was between 22.4 and 32.6% in SIF within 360 min. In vitro sophoridine release studies in successive different mimicking media showed that the guar matrix tablets released 13.5–25.6% of sophoridine in the first 6 h; therefore it was necessary to develop the bilayer matrix tablet by direct-compressing coating 100 mg guar granula on core tablet. The initial release of coated tablet was retarded and the bilayer matrix tablet was suitable for colon target.     

Studies of Guar Gum Compression-Coated 5-Aminosalicylic Acid Tablets for Colon-Specific Drug Delivery

The aim of this study was to develop colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) using guar gum as a carrier. Core tablets containing 5-ASA were prepared by wet granulation with starch paste and were compression coated with coating formulations containing different quantities of guar gum (300, 200, 150, and 125 mg). In vitro drug release studies were carried out in simulated gastric and intestinal fluids and in pH 6.8 buffer containing rat cecal contents. The application of 175 mg of coating formulation containing 150 mg of guar gum over 5-ASA core tablets resulted in the release of less than 2% drug in simulated gastric and intestinal fluids and about 93% of 5-ASA in pH 6.8 buffer containing rat cecal contents. Differential scanning calorimetric (DSC) studies showed the absence of any interaction between 5-ASA and the excipients on storage at 45°C for 12 weeks. The study confirmed that selective delivery of 5-ASA to the colon can be achieved using guar gum as a carrier in the form of a compression coating over the drug core.     

Studies of guar gum compression-coated 5-aminosalicylic acid tablets for colon-specific drug delivery

The aim of this study was to develop colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) using guar gum as a carrier. Core tablets containing 5-ASA were prepared by wet granulation with starch paste and were compression coated with coating formulations containing different quantities of guar gum (300, 200, 150, and 125 mg). In vitro drug release studies were carried out in simulated gastric and intestinal fluids and in pH 6.8 buffer containing rat cecal contents. The application of 175 mg of coating formulation containing 150 mg of guar gum over 5-ASA core tablets resulted in the release of less than 2% drug in simulated gastric and intestinal fluids and about 93% of 5-ASA in pH 6.8 buffer containing rat cecal contents. Differential scanning calorimetric (DSC) studies showed the absence of any interaction between 5-ASA and the excipients on storage at 45°C for 12 weeks. The study confirmed that selective delivery of 5-ASA to the colon can be achieved using guar gum as a carrier in the form of a compression coating over the drug core.     

Chitosan and Sodium Sulfate as Excipients in the Preparation of Prolonged Release Theophylline Tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron® tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Chitosan and sodium sulfate as excipients in the preparation of prolonged release theophylline tablets

The major objectives of this study were to monitor the effect of cross-linking of cationic chitosan in acidic media with sulfate anion during granules preparation by wet granulation method prior to tableting using theophylline (TPH) as a model drug. The prepared granules and the compressed tablets were subjected to in vitro evaluation. The properties of the prepared matrix granules and the compressed tablets were dependent on chitosan:sodium sulfate weight ratios, chitosan content, and molecular weight of chitosan. The prepared granules of all batches showed excellent to passable flowability and were suitable for compression into tablets. Most of the granules were hard and expected to withstand handling during the subsequent compression into tablets. Granules with high friabilities were only those prepared with a high amount of sodium sulfate or low amount of chitosan. Compression of granule batches yield nondisintegrating tablets that showed a decrease in tensile strength with the increase of sodium sulfate content at high chitosan:sodium sulfate weight ratio or with decrease of chitosan content. On the other hand, friability of tablets was increased in the presence of an excessive amount of sodium sulfate and low chitosan content as observed with granules. Slow TPH release from the formulated tablets was achieved at 1:0.5 and 1:1 chitosan:sodium sulfate weight ratios where all or most of the cationic chitosan and sulfate anions were used in a cross-linking reaction during wet granulation. Ratios of 1:2 and 1:3 showed fast drug release, which support the hypothesis that excessive unreacted water-soluble sodium sulfate might increase the porosity of the nondesintegrating tablets during dissolution. Slow drug release was also obtained with high molecular weight chitosan, whereas changing the hardness of the tablets did not significantly change the release profile of the drug as long as the tablets are intact during dissolution. Furthermore, slow drug release was observed as the total amount of chitosan was increased in the formulated tablets. A comparative in vivo study between the chosen formulated tablets (1:1 chitosan:sodium sulfate ratio that contains 10% high molecular weight chitosan) and the commercial Quibron tablets indicated prolonged appearance of the drug in dogs' plasma for both formulations with no significant differences (p > 0.05) in rate and extent of drug absorption. The formulated tablets showed 103.16% bioavailability relative to that of the commercial tablets.     

Preparation and Evaluation of Directly-Compressed Indomethacin, Indomethacin Sodium and Indomethacin Meglumine Tablets

A formula containing Compactrol, Ac-Di-Sol, Aerosil 200 and talc was used to prepare directly-compressed tablets of indomethacin and its sodium and meglumine salts. The prepared tablets were evaluated for uniformity of weight and thickness, hardness, friability and content uniformity. Each batch was then divided into two, one was coated with an opaque non-enteric film coat and evaluated for coat thickness uniformity. The dissolution rates of the uncoated and coated tablets and the effect of shelf-storage, at room temperature for 11 months, on drug contents were also studied. Indomethacin meglumine tablets showed the least relative standard deviation of weight and thickness. They exhibited acceptable uniformity of content and coat thickness, and the highest hardness-friability ratio. Also exhibited, uncoated and coated, the best in-vitro release of its drug contents and the maximal stability.