Formulation and characterization of colon specific drug delivery system of prednisolone

Abstract

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.