Compaction, compression and drug release properties of diclofenac sodium and ibuprofen pellets comprising xanthan gum as a sustained release agent

Compaction and compression of xanthan gum pellets were evaluated and drug release from tablets made of pellets was characterised. Two types of pellets were prepared by extrusion-spheronisation. Formulations included xanthan gum, at 16% (w/w), diclofenac sodium or ibuprofen, at 10% (w/w), among other excipients. An amount of 500 mg of pellets fraction 1000-1400 microm were compacted in a single punch press at maximum punch pressure of 125 MPa using flat-faced punches (diameter of 1.00 cm). Physical properties of pellets and tablets were analysed. Laser profilometry analysis and scanning electron microscopy of the upper surface and the surface of fracture of tablets revealed that particles remained as coherent individual units after compression process. Pellets were flatted in the same direction of the applied stress evidencing a lost of the original curvature of the spherical unit. Pellets showed close compressibility degrees (49.9% for pellets comprising diclofenac sodium and 48.5% for pellets comprising ibuprofen). Xanthan gum pellets comprising diclofenac sodium experienced a reduction of 65.5% of their original sphericity while those comprising ibuprofen lost 49.6% of the original porosity. Permanent deformation and densification were the relevant mechanisms of compression. Fragmentation was regarded as non-existent. The release of the model drug from both type of tablets revealed different behaviours. Tablets made of pellets comprising ibuprofen released the model drug in a bimodal fashion and the release behaviour was characterised as Case II transport mechanism (release exponent of 0.93). On the other hand, the release behaviour of diclofenac sodium from tablets made of pellets was anomalous (release exponent of 0.70). For the latter case, drug diffusion and erosion were competing mechanisms of drug release.     

Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum

The aim of this study was to investigate the influence of pH, buffer species and ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets containing chitosan and xanthan gum prepared by a hot-melt extrusion process. Drug release from hot-melt extruded (HME) tablets containing either chitosan or xanthan gum was pH and buffer species dependent and the release mechanisms were controlled by the solubility and ionic properties of the polymers. All directly compressed (DC) tablets prepared in this study also exhibited pH and buffer species dependent release. In contrast, the HME tablets containing both chitosan and xanthan gum exhibited pH and buffer species independent sustained release. When placed in 0.1N HCl, the HME tablets formed a hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4 phosphate buffers even when media contained high ionic strength, whereas tablets without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The HME tablets containing both chitosan and xanthan gum showed no significant change in drug release rate when stored at 40 °C for 1 month, 40 °C and 75% relative humidity (40 °C/75% RH) for 1 month, and 60 °C for 15 days.     

Development and Evaluation of Microbial Degradation Dependent Compression Coated Secnidazole Tablets for Colonic Delivery

The present paper describes development of a polysaccharide based compression coated tablets of secnidazole for colon delivery. Core tablet containing secnidazole was compression coated with various proportions of guar gum, xanthan gum and chitosan, either alone or in combinations. Drug release studies were performed in simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF, pH 7.4) up to 24 h. Secnidazole release from the prepared formulations was dependent on the type and concentration of polymer used in the formulation. Tablets coating containing either guar gum or xanthan gum showed ~30-40% drug release in 8 h. Further, in vitro dissolution studies of selected formulations performed in the dissolution media with rat caecal contents showed 54.48±0.24 - 60.42±0.16% of drug release. Formulations with single polymer in coating layer were unsuitable for targeting secnidazole release to colon region. Combination of chitosan with guar gum or xanthan gum exhibited control over secnidazole release.     

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8–12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.     

Compression coated systems for colonic delivery of 5-fluorouracil

Compression coating is one of the approaches for delaying the release of drugs. The aim of this study was to develop colon-specific compression coated systems of 5-fluorouracil (5-FU) for the treatment of colorectal cancer using xanthan gum, boswellia gum and hydroxypropyl methylcellulose (HPMC) as the coating materials. Core tablets containing 50 mg of 5-FU were prepared by direct compression. The coating of the core tablets was done using different coat weights (230, 250, 275 and 300 mg) and different ratios (1:2, 2:1, 1:3, 1:7 and 3:4) of boswellia gum and xanthan gum and different ratios (1:1, 1:2, 2:1, and 2:3) of boswellia gum and HPMC. In-vitro release studies were carried out using simulated gastric and intestinal fluids, with and without rat caecal contents. Among the different ratios used for coating with boswellia:xanthan gum combination, ratio 1:3 gave the best release profile with the lowest coating weights of 230 mg (7.47 +/- 1.56% in initial 5 h). Further increase in the coat weights to 250, 275 and 300 mg led to drug release of 5.63 +/- 0.53%, 5.09 +/- 1.56% and 4.57 +/- 0.88%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. When coating was carried out using different ratios of the combination boswellia gum and HPMC, the ratio 2:3 gave the best results among the initial trial batches (7.80 +/- 0.57% in 5 h). Increasing the coat weights to 250, 275 and 300 mg led to drug release of 6.5 +/- 0.27%, 3.70 +/- 2.3% and 2.99 +/- 0.72%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. In-vitro studies were further carried out in the presence of 2% w/v rat caecal contents, which led to complete release of the drug from the tablets. Therefore, this study lays a basis for use of compression coating of 5-FU as a tool for delaying the release of the drug, which ensures better clinical management of the disease.     

Suitability of κ-carrageenan pellets for the formulation of multiparticulate tablets with modified release

κ-Carrageenan is a novel pelletisation aid with high formulation robustness and quick disintegration leading to fast drug release unlike the matrix-like release from non-disintegrating microcrystalline cellulose pellets. Compression of pellets into tablets is cost effective. The feasibility of formulating multiparticulate tablets with coated κ-carrageenan pellets was investigated. Pellets containing a highly soluble drug in acid, namely bisacodyl and κ-carrageenan or MCC as pelletisation aid were prepared, enteric coated with a mixture of Kollicoat(?) MAE 30 DP and Eudragit(?) NE 30 D and compressed using silicified microcrystalline cellulose as embedding powder. The effect of coating level, type of pellet core, compression force and punch configurations on drug release were studied. A sufficient coating thickness for κ-carrageenan pellets was necessary to obtain multiparticulate tablets with adequate resistance in the acid stage regardless of the compression pressure used. While κ-carrageenan pellets and their tablets released over 80% of the drug during the neutral stage only about 20-24% was released from MCC pellets and their tablets. The type of punches used (oblong or round) did not significantly influence the drug release from the prepared tablets. Moreover, sufficient prolonged release properties were obtained with κ-carrageenan pellets containing theophylline as a model drug and coated with Kollicoat(?) SR 30 D using Kollicoat(?) IR as pore former. A lower coating level and higher amount of pore former were needed in case of theophylline pellets formulated with MCC as pelletisation aid. The sustained release properties of both coated pellet formulations were maintained after compression at different compression pressures.     

黄原胶亲水性骨架片体外释药的影响因素

以茶碱为模型药物,制备了黄原胶亲水性骨架片,研究了体外释药的影响因素．结果表明,茶碱黄原胶亲水性骨架片的释药速率与骨架片中黄原胶的用量和溶出条件（ 转速、介质离子强度、ｐＨ 值） 有关,但与制备工艺条件无关．溶出介质中离子对其释药机制有影响．黄原胶能有效控制骨架片中药物释放,是一种优良的亲水性骨架材料．     

Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion

Mini-matrices (multiple unit dosage form) with release-sustaining properties were developed by hot-melt extrusion (cylindrical die: 3 mm) using metoprolol tartrate as model drug and ethylcellulose as sustained-release agent. Dibutyl sebacate was selected as plasticizer and its concentration was optimized to 50% (w/w) of the ethylcellulose concentration. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase drug release. Changing the xanthan gum concentration modified the in vitro drug release: increasing xanthan gum concentrations (1%, 2.5%, 5%, 10% and 20%, w/w) yielded a faster drug release. Zero-order drug release was obtained at 5% (w/w) xanthan gum. Using kneading paddles, smooth extrudates were obtained when processed at 60 °C. At least one mixing zone was required to obtain smooth and homogeneous extrudates. The mixing efficacy and drug release were not affected by the number of mixing zones or their position along the extruder barrel. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of screw design and processing conditions. Simultaneously changing the powder feed rate (6–25–50 g/min) and screw speed (30–100–200 rpm) did not alter extrudate quality or dissolution properties.     

Synthesis,characterization and evaluation of deacetylated xanthan derivatives as new excipients in the formulation of chitosan-based polyelectrolytes for the sustained release of tramadol

This paper addressed the application of deacetylated xanthan (XGDS) and chitosan (CTS) as a mixture blend forming hydrophilic matrices for Tramadol (TD) sustained release tablets. XGDSs derivatives were obtained by alkaline treatment of xanthan gum (XG) with various degrees of deacetylation (DD). The obtained products were characterized in terms of structural, thermal and physicochemical properties. Different tablet formulations containing CTS/XGDSs were prepared by direct compression method and compared to CTS/XG tablets. Flow properties of powder mixtures and pharmaceutical characteristics were evaluated. The dissolution test of TD was realized under simulated gastric and intestinal conditions to achieve drug release more than 24 h. All developed tablets were found conforming to standard evaluation tests. It was shown that CTS/XGDSs matrices ensure a slower release of TD in comparison with CTS/XG based formulations. Meanwhile, increasing DD resulted in a decrease of drug release. In addition, TD release from XGDS matrices was faster at pH (6.8) than at acidic pH (1.2). The matrix tablets based on CTS/XGDS4 (DD = 98.08%) were selected as the best candidates compared to the other systems in prolonging drug release. The optimal formulation was found to release 99.99% of TD after 24 h following a non-Fickian type.     

Xanthan gum to tailor drug release of sustained-release ethylcellulose mini-matrices prepared via hot-melt extrusion: in vitro and in vivo evaluation.

Mini-matrices (multiple-unit dosage form) with release-sustaining properties were developed by means of hot-melt extrusion using ibuprofen as the model drug and ethylcellulose as sustained-release agent. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase the drug release since ibuprofen release from the ibuprofen/ethylcellulose matrices (60/40, w/w) was too slow (20% in 24 h). Changing the xanthan gum concentration as well as its particle size modified the in vitro drug release. Increasing xanthan gum concentrations yielded a faster drug release due to a higher liquid uptake, swelling and erosion rate. Regarding the effect of the xanthan gum particle size, no difference was observed for formulations containing 10% and 20% xanthan gum. However, using 30% xanthan gum, drug release was influenced by the particle size of the hydrophilic polymer due to the susceptibility of the coarser xanthan gum particles to erosion. Drug release from the mini-matrices was mainly diffusion controlled, but swelling played an important role to obtain complete drug release within 24 h. Drug release was influenced by the ionic strength of the medium as the conformation of xanthan gum molecules is determined by the salt concentration. An oral dose of 300 mg ibuprofen was administered to dogs (n=6) in a cross-over study design either as an immediate-release preparation (Junifen), as a sustained-release formulation (Ibu-Slow 600 mg (1/2 tablet)) or as the experimental mini-matrices (varying in xanthan gum concentration). Administration of the experimental formulations sustained the ibuprofen release. Although a significant difference in dissolution rate of the 20% and 30% xanthan gum mini-matrices was detected in vitro, the difference in relative bioavailability was limited (70.6% and 73.8%, respectively).     

Compression of pellets coated with various aqueous polymer dispersions

Pellets coated with a new aqueous polyvinyl acetate dispersion, Kollicoat SR 30 D, could be compressed into tablets without rupture of the coating providing unchanged release profiles. In contrast, the compression of pellets coated with the ethylcellulose dispersion, Aquacoat ECD 30, resulted in rupture of the coating and an increase in drug release. Plasticizer-free Kollicoat SR coatings were too brittle and ruptured during compression. The addition of only 10% w/w triethyl citrate as plasticizer improved the flexibility of the films significantly and allowed compaction of the pellets. The drug release was almost independent of the compression force and the pellet content of the tablets. The inclusion of various tabletting excipients slightly affected the drug release, primarily because of a different disintegration rate of the tablets. The core size of the starting pellets had no influence on the drug release. Pellets coated with the enteric polymer dispersion Kollicoat 30 D MAE 30 DP [poly(methacrylic acid, ethyl acrylate) 1:1] lost their enteric properties after compression because of the brittle properties of this enteric polymer. Coating of pellets with a mixture of Kollicoat MAE 30 DP and Kollicoat EMM 30 D [poly(ethyl acrylate, methyl methacrylate) 2:1] at a ratio of 70/30 and compaction of the pellets resulted in sufficient enteric properties.     

Colonic drug delivery of 5-fluorouracil: an in vitro evaluation

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to design a formulation with a considerably reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil for the treatment of colorectal cancer. Rapidly disintegrating core tablets containing 50 mg of 5-fluorouracil were prepared and compression coating with 175 mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in varying proportions was done. With this coat weight, a highly retarded drug release was observed. After 24h of dissolution the mean percent drug release from the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be around 18+/-1.23%, 20+/-1.54% and 30+/-1.77%, respectively. So, the coat weight was further reduced to 150 mg. It was observed that reduction of coat weight did not affect the initial drug release rate in simulated upper gastrointestinal tract (GIT) conditions. At the end of 24h of dissolution the amount of drug released increased to 25+/-1.22%, 36.6+/-1.89% and 42.6+/-2.22%, respectively in XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in presence of colonic contents showed an increased cumulative percent drug release of 67.2+/-5.23% in presence of 2% cecal content and 80.34+/-3.89% in presence of 4% cecal content after 19 h of incubation.     

Use of natural gums and cellulose derivatives in production of sustained release metoprolol tablets

Metoprolol tartrate sustained-release tablets (100 mg) were prepared using xanthan/guar gums and also hydroxypropyl methyl cellulose (HPMC) carboxymethyl-Cellulose (CMC) polymers by direct compression method. Physical characteristics of the tablets and water uptake in addition to their dissolution profiles were compared with standard (Lopressor® SR) tablets. Dissolution test was performed in the phosphate buffer solution (pH 6.8) and the samples were analyzed spectrophotometerically in 275.7 nm. Dissolution studies showed that formulations containing 100 and 80% of HPMC, 100% of guar, and 20% of xanthan followed the Higuchi model, while those containing 60 and 40% HPMC and 100 and 80% xanthan followed a zero-order model. The tablets with 40% xanthen followed a Hixon-Crowell model. In cellulose derivatives the highest MDT and dissolution efficiency until 8 hr (DE₈%) belonged to tablets with 40% HPMC, increasing the amount of CMC decreased the drug release rate, and formulations containing 60 and 40% of HPMC had the USP dissolution standards. While, in the gum formulations, the highest mean dissolution time and the lowest DE₈% belonged to tablets with 100% xanthan, increasing the xanthan decreased the release rate of metoprolol, and formulations containing 80 and 100% xanthan had the USP dissolution standards. Results showed that natural gums are suitable for production of sustained-release tablets of metoprolol.     

Formulation and In vitro assessment of sustained release terbutaline sulfate tablet made from binary hydrophilic polymer mixtures

In the present systematic study, a sustained release of terbutaline sulfate tablet (TBS) was developed and optimized by employing the hydrophilic polymers; chitosan and xanthan gum mixed with sodium bicarbonate as a release modifying agent. This formulation was developed using direct compression technology. In vitro release studies indicated rapid swelling and drug release in the initial period of the acid stage from a matrix composed of chitosan and xanthan gum solely. Addition of sodium bicarbonate to the matrix resulted in sustained drug release. Various formulation factors such as polymer to polymer ratio, polymer viscosity and particle size were altered and their effect on dissolution pattern was illustrated. Manufacturing variables such as compression force and lubricant percentage were investigated and found not to influence the drug release profile of the resulted tablets. The release mechanism follows Korsmeyer-Peppas equation with n value indicating non-Fickian diffusion. The release profiles were analyzed using statistical method (one-way ANOVA) and f₂ metric values and found to be similar to the commercial product Bricanyl^®. Reproducible data were obtained when scale-up of the formulation was performed.     

Evaluation of guar gum as a compression coat for drug targeting to colon

Colon-specific drug delivery systems based on a polysaccharide, guar gum, were evaluated using in vitro and in vivo methods. In vitro drug release studies have shown that guar gum in the form of compression coat applied over indomethacin core tablets protects the drug from being released under conditions mimicking mouth to colon transit. Studies in pH 6.8 phosphate buffered saline (PBS) containing 4% w/v rat caecal contents have demonstrated the susceptibility of guar gum to the colonic bacterial enzyme action with consequent drug release. gamma-scintigraphic studies in human volunteers with technetium-99m-DTPA as a tracer in sodium chloride core tablets compression coated with guar gum have shown that the gum coat protect the drug (tracer in the present study) from being released in the stomach and small intestine. On entering the ascending colon, the tablets commenced to release the tracer indicating the breakdown of the gum coat by the enzymatic action of colonic bacteria. The tablets disintegrated in the ascending colon of all the volunteers, except one, resulting in the distribution of released tracer across the entire colon. The study clearly established that guar gum, in the form of compression coat, is a potential carrier for drug targeting to colon.     

黄原胶与HPMC的凝胶特性及释药机制

采用直接压片法，研究黄原胶与HPMC的凝胶特性。用称重法和体积测量法研究两种辅料分别在0．1mol／L盐酸和pH6．8磷酸盐缓冲液中的水合度及溶胀度，并以阿莫西林为模型药物进行体外释药研究。结果表明，在0．1mol／L盐酸中，HPMC的水合度及溶胀度均大于黄原胶，对药物释放阻滞作用较大；而在pH6．8磷酸盐缓冲液中则相反。药物在两种辅料中可通过骨架溶蚀和(或)凝胶层扩散呈零级或Higuchi型释药。     

Evaluation of the potential use of poly(ethylene oxide) as tablet- and extrudate-forming material

The purpose of this study was to assess the potential use of poly(ethylene oxide) (PEO) as matrix-forming material for tablets and extrudates. Raw materials were characterized for size, size distribution, and shape. Tablets with 2- and 10-mm diameter were prepared by direct compression at both 13 and 38 MPa from mixtures with poly(ethylene oxide)s, a model drug (propranolol hydrochloride) and lactose. To these mixtures water was added (16%-43%) prior to extrusion in a ram extruder fit with different dies (1-, 3-, 6-, and 9-mm diameter and 4-mm length). Tablets and extrudates were characterized for work of compression or extrusion, respectively, relaxation, tensile strength, friability, and drug release. Both PEOs produced tablets easily and with different properties. Some relaxation was observed, particularly for tablets with higher amounts of PEOs. Release of the drug occurred after swelling of the matrix, and between 10% and 70% drug released, a quasi zero-order release was observed for large tablets. Extrusion was possible for formulations with PEO only with amounts of water between 16% and 50%. Both radial and axial relaxation of both plugs and extrudates were observed. Moreover, different extrusion profiles reflected the different behaviors of the different formulations. The model drug was released in the same fashion as observed for the tablets. It was possible to produce tablets by direct compression and extrudates or pellets from those extrudates from different formulations with PEO. Tablets and pellets have shown distinct properties depending upon the PEO considered. Extrusion was particularly complex with different formulations with PEO.     

双氯芬酸钠肠溶微丸型片剂的研制

本文制备了双氯芬酸钠肠溶微丸型片剂。以丙烯酸树脂EudragitNE30D和EudragitL30D-55不同比例的混合物作为衣膜材料，对不同粒径大小的双氯芬酸钠速释丸芯进行不同增重水平的包衣，并与不同压缩特性和用量比例的缓冲微丸混合，压片。所得的双氯芬酸钠肠溶微丸型片剂在人工胃液中2 h内累积释放百分数<10%，在人工肠液中1 h内累积释放百分数为(83±2.42)%。结果表明EudragitNE30D与EudragitL30D-55以一定比例混合制备得到适合压片的肠溶微丸，硬脂酸制备的缓冲微丸可用于微丸型片剂的制备。     

Gastroretentive mucoadhesive tablet of lafutidine for controlled release and enhanced bioavailability

Abstract

Lafutidine a newly developed histamine H2-receptor antagonist having biological half-life of 1.92?±?0.94?h due to its selective absorption from upper part of gastrointestinal tract the development of mucoadhesive sustained release drug delivery system is recommended in order to enhance the bioavailability. A mucoadhesive tablets was developed using the natural polymer, sodium alginate, xanthan gum and karaya gum. Mucoadhesion is a complex phenomenon which involves wetting, adsorption and interpenetration of polymer chains. The prepared tablets of various formulations were evaluated for a total mucoadhesion time, buoyancy lag time and percentage drug released. The formulation with xanthan gum showed better results. Thus, it may be useful for prolonged drug release in stomach to improve the bioavailability and reduced dosing frequency. Non-fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer–Peppas. The optimized formulation (B3) showed a mucoadhesive strength >35?g. In vivo study was performed using rabbits by X-ray imaging technique. Radiological evidences suggest that, a formulated tablet was well adhered for >10?h in rabbit’s stomach. Optimized lafutidine mucoadhesive tablets showed no significant change in physical appearance, drug content, mucoadhesive properties and in vitro dissolution pattern after storage at 40?°C temperature 75?±?5% relative humidity for 3 months.     

The encapsulation of ribozymes in biodegradable polymeric matrices

The aim of the present study is to develop colon targeted drug delivery systems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared. All the formulations were evaluated for the hardness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of metronidazole released from tablets at different time intervals was estimated by high performance liquid chromatography method. Matrix tablets and multilayer tablets of metronidazole released 43-52% and 25-44% of the metronidazole, respectively, in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. Both the formulations failed to control the drug release within 5 h of the dissolution study in the physiological environment of stomach and small intestine. The compression coated formulations released less than 1% of metronidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 275 mg of guar gum coat released another 61% of metronidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 350 and 435 mg of guar gum coat released about 45 and 20% of metronidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated metronidazole tablets with either 275 or 350 mg of guar gum coat is most likely to provide targeting of metronidazole for local action in the colon owing to its minimal release of the drug in the first 5 h. The metronidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months.