Presence Of Rat Caecal Contents Research Articles

Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: A smart pH-responsive and receptor-targeted system for colorectal cancer therapy

Glycosylated pH-sensitive mesoporous silica nanoparticles (MSNs) of capecitabine (CAP) were developed for targeting colorectal cancer. The MSNs possessed an average pore diameter of 8.12 ± 0.43 nm, pore volume of 0.73 ± 0.21 cm3/g, and particle size of 245.24 ± 5.75 nm. A high loading of 180.51 ± 5.23 mg/g attributed to the larger pore volume was observed. The surface of the drug-loaded MSNs were capped with chitosan-glucuronic acid (CHS-GCA) conjugate to combine two strategies viz. pH-sensitive, and lectin receptor mediated uptake. In vitro studies demonstrated a pH-sensitive and controlled release of CAP which was further enhanced in the presence of rat caecal content. Higher uptake of the (CAP-MSN)CHS-GCA was observed in HCT 116 cell lines. The glycosylated nanoparticles revealed reduction in the tumors, aberrant crypt foci, dysplasia and inflammation, and alleviation in the toxic features. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as a effective carrier against cancer.

SYNTHESIS AND CHARACTERIZATION OF THIOLATED JACKFRUIT SEED STARCH AS A COLONIC DRUG DELIVERY CARRIER

Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon.
 Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics.
 Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics.
 Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon.

A NOVEL APPROACH OF LOCUST BEAN GUM MICROSPHERES FOR COLONIC DELIVERY OF MESALAMINE

Objective: The objective of the present study was to formulate site-specific drug delivery of mesalamine using Locust bean gum.Methods: The core microspheres were prepared by ionic gelation method using CaCl2 solution and cross-linked with glutaraldehyde and were further coated with pH-sensitive polymer eudragit S-100(1.5-4.5 ml) to retard the drug release in the upper gastrointestinal environment (Stomach and small intestine). Microspheres were characterized by ftir spectroscopy, differential scanning calorimetry and evaluated by scanning electron microscopy (SEM), particle size analysis, entrapment efficiency and in vitro drug release studies in different simulated gastric fluids. Stability studies were carried out for one month at 40±2 °C/75±5% RH.Results: The SEM images revealed the surface morphology was rough and smooth for core and coated microspheres, respectively. The optimized batch (ILBG6) of core microspheres(for 7hr), coated microspheres and coated microspheres in presence of rat caecal contents (8%w/v) for 24hr exhibited 98.44±2.48, 73.58±3.49 % and 98.28±4.42 drug release, respectively. The drug release from all locust bean gum microsphere formulations followed higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the korsmeyer-peppas equation with an fickian kinetics mechanism. Finally, stability studies suggested the change in entrapment efficiency and in vitro drug release of microspheres was minimal, indicating good stability of the formulation.Conclusion: The microspheres formed using natural polysaccharide locust beangum by ionic gelation method are capable of colon targeting the anti-inflammatory drug, mesalamine for the treatment of ulcerative colitis.

Preparation, Evaluation and Optimization of Multiparticulate System of Mebendazole for Colon Targeted Drug Delivery by Using Natural Polysaccharides.

A Multiparticulate system of Mebendazole was developed for colon targeted drug delivery by using natural polysaccharides like Chitosan and Sodium-alginate beads. Chitosan microspheres were formulated by using Emulsion crosslinking method using Glutaraldehyde as crosslinking agent. Sodium-alginate beads were formulated by using Calcium chloride as gelling agent. Optimization for Chitosan microspheres was carried out by using 2(3) full factorial design. 3(2) full factorial design was used for the optimization of Sodium-alginate beads. The formulated batches were evaluated for percentage yield, particle size measurement, flow properties, percent entrapment efficiency, Swelling studies. The formulations were subjected to Stability studies and In-vitro release study (with and without rat caecal content). Release kinetics data was subjected to different dissolution models. The formulated batches showed acceptable particle size range as well as excellent flow properties. Entrapment efficiency for optimized batches of Chitosan microspheres and sodium alginate beads was found to be 74.18% and 88.48% respectively. In-vitro release of drug for the optimized batches was found to be increased in presence of rat caecal content. The best-fit models were koresmeyer-peppas for Chitosan microspheres and zero order for sodium-alginate beads. Chitosan and Sodium-alginate was used successfully for the formulation of Colon targeted Multiparticulate system.

Colon specific drug delivery of tramadol HCl for chronotherapeutics of arthritis.

Objective:The objective of present work is to develop and evaluate a matrix system for Chronotherapeutic delivery of centrally acting of opioid analgesic (tramadol HCl) to treat nocturnal symptoms of arthritis using almond gum as carrier.Materials and Methods:Matrix tablets of tramadol HCl were prepared by using 30, 40, 50, 60 and 70% w/w of tablet of gum badam as carrier by wet granulation technique. These tablets were compression coated with eudragit S100 to prevent drug release in stomach. All formulations were evaluated for hardness, friability, weight variation, drug content, in vitro and in vivo studies. The almond gum was characterized by viscosity measurements and Fourier transform infrared analysis. The coated (FC1 to FC5) and uncoated tablets (F1 to F5) were evaluated for in vitro release of tramadol HCl after sequential exposure to pH 1.2, pH 7.4 and pH 6.8 respectively for 2 h, 3 h and 19 h in the absence as well as presence of rat caecal content and the corresponding data was fitted to popular release kinetic equations in order to evaluate the release mechanisms-kinetics. The selected formulation was subjected to in vivo targeting efficacy studies by roentgenography technique.Results and Discussion:In vitro release studies indicated that the matrix tablets (F1 to F5) failed to control the drug release in the physiological environment of stomach and small intestine. On the other hand, compression coated formulations were able to protect the tablet cores from premature drug release. Presence of rat caecal content enhances the drug release from the tablets as the concentration of polymer increased, drug release was found to be retarded. The release of tramadol from all the formulation followed zero order with non fickian diffusion. X-ray studies confirmed that the tablet successfully reached colon without getting disintegrated in upper gastrointestinal tract.Conclusion:Based on the results, selective delivery of tramadol HCl to the colon could be achieved using 60% w/w (FC4) of almond gum matrix tablets compression coated with eudragit S100.

Pioglitazone hydrochloride: chemopreventive potential and development of site-specific drug delivery systems

The aim of this study was to investigate the potential of pioglitazone hydrochloride as a promising anticancer agent and then to design and evaluate the colon-targeted delivery system. The role of pioglitazone hydrochloride as a promising anticancer agent was evaluated by in vitro cell line studies and in vivo 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. In order to deliver the drug at site of action, i.e. colon, drug embedded in matrices containing a release retarding polymer (HPMC K4M) and a polysaccharide (locust bean gum) were prepared. These matrix systems were further enteric coated with Eudragit®S100 to minimize the premature drug release in the upper segments of the GIT. In vitro dissolution studies were performed in absence and presence of rat caecal contents on selected batches and samples were analyzed using a validated RP-HPLC method. Hence, the studies led to the conclusion that successful site-specific delivery systems of pioglitazone hydrochloride were developed to improve its therapeutic efficacy in the management of colorectal cancer.

Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

Fabrication and Evaluation of Tinidazole Microbeads for Colon Targeting

ObjectiveThe purpose of present investigation was to develop and evaluate multiparticulate system exploiting pH-sensitive property and specific biodegradability of calcium alginate microbeads, for colon-targeted delivery of Tinidazole for the treatment of amoebic colitis. MethodsCalcium alginate beads containing Tinidazole were prepared by ionotropic gelation technique followed by coating with Eudragit S100 using solvent evaporation method to obtain pH sensitive microbeads. Various formulation parameters were optimized which included concentration of sodium alginate (2% w/v), curing time (20 min) and concentration of pectin (1% w/v). All the formulations were evaluated for surface morphology, particle size analysis, entrapment efficiency and in-vitro drug release in conditions simulating colonic fluid in the presence of rat caecal (2% w/v) content. ResultsThe average size of beads of optimized formulation (FT4) was found to be 998.73±5.12 μm with entrapment efficiency of 87.28±2.19 %. The invitro release of Eudragit S100 coated beads in presence of rat caecal content was found to be 70.73%±1.91% in 24 hours. Data of in-vitro release was fitted into Higuchi kinetics and Korsmeyer Peppas equation to explain release profile. The optimized formulation (FT4) showed zero order release. ConclusionsIt is concluded that calcium alginate microbeads are the potential system for colon delivery of Tinidazole for chemotherapy of amoebic infection.

Formulation and characterization of colon specific drug delivery system of prednisolone

Background: Enteric-coated systems are most commonly used for colonic drug delivery and constitute a majority of commercially available preparations for colon targeting. This pH variation in different segments of gastrointestinal has been exploited for colon-specific delivery. Coating the drug core with pH-sensitive polymers, these polymers are insoluble in acidic media, but dissolves at a pH of 6 or more, thereby providing protection to the drug core in the stomach and to some extent in the SI releasing the drug in the colon. Aim: The present study aimed to statistically optimize a colon-specific drug delivery system of prednisolone for the treatment of inflammatory bowel disease. Materials and Methods: A 3 2 full factorial design was used for optimization. The independent variables employed were amount of hydroxyethyl guar (HEG) and % CWG each at three levels. The dependent variables were % CDR at 5 hours, % CDR at 12 hours, and t50% (time required for 50% drug release). The tablets were prepared by the wet granulation method using novel guar gum derivative HEG as a polysaccharide. The formulated tablets were evaluated for weight variation, thickness, hardness, friability, drug content, and swelling index. The tablets were coated with 10% w/v solution of Eudragit L100 and Eudragit S100 (1:4) in IPA using 20% w/w triethyl citrate as plasticizer. The coated tablets were evaluated for in vitro dissolution studies in different pH media mimicking the transit of tablet from stomach to colon. Results and Conclusions: Differential scanning calorimetry studies showed no incompatibility of drug with other excipients. The optimized formulation F9 containing 30% HEG and 9% CWG showed 10.09% drug release after 5 hours (lag phase) and 60.76% drug release after 12 hours. Drug release was accelerated in the presence of rat caecal contents and indicated the degradation of polysaccharide by colonic microflora. The optimized formulation was subjected to an in vivo X-ray imaging study in albino rabbit to trace the movement and behavior of the tablet in gastrointestinal tract. A short-term stability study of the optimized formulation showed no significant changes in physical appearance, drug content, and in vitro dissolution profile when stored at 40 ± 2°C/75 ± 5% RH for 3 months. The designed system can be potentially used as a carrier for colon delivery of prednisolone by regulating drug release in stomach and small intestine.

In vitro evaluation of Moringa oleifera gum for colon- specific drug delivery

Background:Moringa gum obtained from stem of the plant Moringa oleifera Lam. belonging to family Moringaceae. Number of naturally occurring polysaccharides obtained from plant (guar gum, inulin), animal (chitosan, chondrotin sulphate), algal (alginates) or microbial (dextran) origin.Objective:The present study was evaluated Moringa oleifera gum as a carrier for colon specific drug delivery using in vitro drug release studies.Materials and Methods:Six formulations of curcumin were prepared using varying concentration of Moringa oleifera gum containing 50 mg curcumin by wet granulation method. Tablets were subjected for evaluation by studying the parameter like hardness, friability, drug content uniformity and in vitro drug release study. Hardness was found to be in the range of 5.5 to 7.3 kg/cm2, the percentage friability was in the range of 0.60 to 0.89%, and tablet showed 98.99% to 99.89% of the labeled amount of curcumin indicating uniformity in drug content.Results and Discussion:In vitro drug release study was performed using simulated stomach, intestinal and colonic fluid. The susceptibility of Moringa gum to colonic bacteria was also assessed using drug release study with rat caecal contents. 30% Moringa gum containing formulation (F-3) was shown better drug released that is 90.46%, at the end of 24 h of dissolution study in the presence of rat caecal contents in comparison to 40% Moringa gum containing formulation (F-4) that was 78.03%.Conclusion:The results illustrate the usefulness of Moringa olefera gum as a potential carrier for colon-specific drug delivery.

Colon specific chitosan microspheres for chronotherapy of chronic stable angina

In the present work, chitosan microspheres with a mean diameter between 6.32μm and 9.44μm, were produced by emulsion cross-linking of chitosan, and tested for chronotherapy of chronic stable angina. Aiming at developing a suitable colon specific strategy, diltiazem hydrochloride (DTZ) was encapsulated in the microspheres, following Eudragit S-100 coating by solvent evaporation technique, exploiting the advantages of microbiological properties of chitosan and pH dependent solubility of Eudragit S-100. Different microsphere formulations were prepared varying the ratio DTZ:chitosan (1:2 to 1:10), stirring speed (1000–2000rpm), and the concentration of emulsifier Span 80 (0.5–1.5% (w/v)). The effect of these variables on the particle size and encapsulation parameters (production yield (PY), loading capacity (LC), encapsulation efficiency (EE)) was evaluated to develop an optimized formulation. In vitro release study of non-coated chitosan microspheres in simulated gastrointestinal (GI) fluid exhibited a burst release pattern in the first hour, whereas Eudragit S-100 coating allowed producing systems of controlled release diffusion fitting to the Higuchi model, and thus suitable for colon-specific drug delivery. DSC analysis indicated that DTZ was dispersed within the microspheres matrix. Scanning electron microscopy revealed that the microspheres were spherical and had a smooth surface. Chitosan biodegradability was proven by the enhanced release rate of DTZ in presence of rat caecal contents.

Colon Targeted Curcumin Delivery Using Guar Gum

Curcumin is used in the treatment of colon cancer, but its very poor absorption in the upper part of the GIT is a major concern. As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and an increased responsiveness to absorption enhancers. The aim of the present study was to identify a suitable polymer (guar gum) based matrix tablet for curcumin with sufficient mechanical strength and promising in vitro mouth-to-colon release profile. Three formulations of curcumin were prepared using varying concentrations of guar gum containing 50 mg curcumin by the wet granulation method. Tablets were subjected to evaluation by studying parameter like hardness, friability, drug content uniformity, and in-vitro drug release. In vitro drug release was evaluated using simulated stomach, intestinal and colonic fluids. The susceptibility of guar gum to colonic bacteria was also assessed by a drug release study with rat caecal contents. The 40% guar gum containing formulation (F-1) showed better drug release (91.1%) after 24 hours in the presence of rat caecal contents in comparison with the 50% guar gum containing formulation (F-2) (82.1%). Curcumin could, thus, be positively delivered to the colon for effective colon cancer treatment using guar gum.

Probiotic-assisted colon-specific delivery of diclofenac sodium from guar gum matrix tablets: In vitro evaluation

Purpose: The aim of present work was to investigate the in vitro release profile of diclofenac sodium from matrix tablets,which were prepared using guar gum with and without probiotics. Methods: Six matrix tablets formulations (F1-F6) of diclofenac sodium containing varying proportions of guar gum, 10-60% of tablet weight were prepared by wet granulation method and evaluated in vitro for their release profile. Four matrix tablets formulations (F7-F10) of diclofenac with guar gum (40%) were prepared incorporating varying concentration of commercial spores of lactobacillus and bifidobacterium species that are commonly found in colon microflora. Results: The tablets having same concentration of guar gum without probiotics (F4) showed a 54.47% cumulative release of diclofenac after 24 hr while that in presence of probiotics (F9) was 73.01%. These drug release studies were conducted without rat caecal content. In another set of experiments, the drug release studies were carried out in presence of rat caecal content. In such experiments, more than 95% drug was released from F4 and F9 formulations after 24 hr. Conclusion:The results showed that commercial probiotics are capable in digesting guar gum. These probiotics may be used to assist in colon delivery of drugs from formulations prepared with guar gum.

Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit® S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4229–4236, 2009

Methotrexate Bearing Calcium Pectinate Microspheres: A Platform to Achieve Colon-Specific Drug Release

In the present work calcium pectinate (Ca-pectinate) microspheres were prepared to deliver methotrexate in the environment of colon. Calcium pectinate microspheres were prepared by modified emulsification method using calcium chloride as cross linker. All the formulations were evaluated for various physicochemical parameters. Particle size of the microspheres was determined using laser diffraction particle size analyzer. Encapsulation efficiency was determined by digesting with enzyme pectinase for 24 hours and swellability by equilibrium swelling in simulated gastrointestinal fluid. The in vitro drug release studies were performed in simulated gastric fluid for 2 hours and simulated intestinal fluid for 3 hours. In vitro release rate studies were also carried out in simulated colonic fluid in presence of rat caecal contents. Moreover, release rate studies were also carried out after enzyme induction by treating the rats with 1 ml of 1% w/v aqueous dispersion of pectin for 7 days. Mean particle size of the microspheres was found to be in the range of 20.82+/-1.34 to 32.26+/-1.59 microm whereas the entrapment efficiency varied from 52.28+/-0.32 to 74.01+/-3.32%. The in vitro drug release studies in simulated gastric fluid and simulated intestinal fluid showed that only 8.15+/-0.49% drug was released in 5 hours whereas most of the loaded drug was released in simulated colonic fluid containing pectinase. In vitro release rate study showed release of 69.94+/-3.46% of drug in presence of 3% rat caecal contents, which was further increased to 94.43+/-4.48% when enzyme induction was carried out for 7 days. Thus, it is concluded that calcium pectinate microspheres can be used to effectively localize the release of drug in the physiological environment of colon.

Characterization of calcium alginate beads of 5-fluorouracil for colon delivery

Amultiparticulate system combining pH-sensitive property and specific biodegradability for colon targeted delivery of 5-fluorouracil (5-FU) was examined. The purpose of this study was to prepare and evaluate the colon-specific alginate beads of 5-FU for the treatment of colon cancer. Calcium alginate beads were prepared by extruding 5-FU loaded alginate solution to calcium chloride solution, and gelled spheres were formed instantaneously by ionotropic gelation reaction using different ratios of FU and alginate, alginate and calcium chloride, stirring speeds (500-1500 rpm), and reaction time. The core beads were coated with Eudragit S-100 to prevent drug release in the stomach and provide controlled dissolution of enteric coat in the small intestine and maximum drug release in the colon. Morphology and surface characteristics of the formulation were determined by scanning electron microscopy. In vitro drug release studies were performed in conditions simulating stomach to colon transit. No significant release was observed at acidic pH, however, when it reached the pH where Eudragit S-100 starts to dissolve, drug release was observed. Also, release of drug was found to be higher in presence of rat caecal content.

Development of colon-targeted albendazole-β-cyclodextrin-complex drug delivery systems

Albendazole, a drug for the treatment of gastrointestinal nematode infection, is variably and erratically absorbed from the gastrointestinal tract after oral administration. The present study was aimed at developing matrix tablets of albendazole using guar gum as carrier for colon targeting in order to provide an effective and safe therapy for helminthiasis. To improve its bioavailability, the formation of inclusion complexes of albendazole with β-cyclodextrins was investigated. Matrix tablets of albendazole–β-cyclodextrin complex were prepared by the wet granulation method using guar gum as matrix carrier in various proportions: 20% (SAC-20), 30% (SAC-30), and 40% (SAC-40). A high-performance liquid chromatography–ultraviolet method was developed to quantitate albendazole using mebendazole as internal standard at 254 nm. The granules were compressed using 12-mm round, flat, and plain punches. Tablets were evaluated for various physical characteristics such as thickness, hardness, and drug content uniformity. The matrix tablets were subjected to in vitro drug release studies in 0.1 N HCl (2 h), pH 7.4 Sorensen's phosphate buffer (3 h) and simulated colonic fluids. The SAC-30 released 67.7±1.9% of albendazole in the presence of rat caecal contents, whereas in the control study the formulation released only 29.7±0.2% of albendazole. A significant difference (P<0.001) was observed at 24 h in the amount of albendazole released from SAC-30 when compared to the dissolution study without rat caecal contents. The study shows that the release of albendazole in the physiological environment of colon is due to the microbial degradation of guar gum compression-coated tablets in the presence of rat caecal contents. Stability studies were carried out at 40°C/75% relative humidity for 6 months to assess their long-term (2 years) stability. No change either in their physical appearance or in drug content was observed. Drug Dev. Res. 65:76–83, 2005. © 2005 Wiley-Liss, Inc.

Design and Development of Multiparticulate System for Targeted Drug Delivery to Colon

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit® L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit® microspheres, forming a multireservoir system. By coating the microspheres with Eudragit® pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit® starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents.

Chondroitin sulfate: A potential biodegradable carrier for colon-specific drug delivery

Chondroitin sulfate, a soluble mucopolysaccharide utilized as a substrate by the bacteroid inhabitants of the colon, was cross-linked and formulated in a matrix form with indomethacin as a drug marker. Three levels of cross-linkage were used. Cross-linkage was characterized qualitatively by IR spectral analysis and by UV absorbance shifts in hydroalcoholic solutions; it was also characterized quantitatively by comparing the amount of methylene blue remaining after adsorption (at equilibrium) onto the cross-linked product vs that remaining after adsorption onto untreated Chondroitin. The indomethacin release kinetics from the various formulations was analyzed in phosphate-buffered saline (PBS) with and without rat caecal content at 37°C under a CO 2 atmosphere. In separate experiments the caecal content was sonicated to cause lysis of the bacterial cell membranes. The drug release profiles indicated a constant rate of biodegradation in the presence of rat caecal content, and diffusion-driven release from the matrix's surface area in PBS control. Prolonged incubation in PBS with rat caecal content increased drug release, and by 28 h the released indomethacin levels were significantly higher than those in the PBS controls. The maximal cumulative percent release values for the PBS controls were: 30.1 ± 10.0, 19.7 ± 15.0, 9.0 ± 4.1 for the three levels of cross-linkage of the Chondroitin sulfate carriers, respectively, while those for the caecal content media were 71.0 ± 19.0, 48.7 ± 35.0, and 22.5 ± 7.9, respectively. It was concluded that the indomethacin release from these systems was dependent upon the biodegradation action of the caecal content. The linear correlation between the degree of cross-linkage and the amount of drug released in the presence of caecal content suggests that drug release in the colon can be controlled by adjusting the relative amounts of the variously cross-linked Chondroitin sulfate formulations in the matrices.