Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes
Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3？:？2？>？2？:？3？>？1？:？1 ratios of CS and EL. An electrostatic interaction between the carbonyl (–CO–) group of EL and amino (– ) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs. 1. Introduction In recent years, various strategies have been adopted for specific drug delivery to well-defined sites of the gastrointestinal (GI) tract, the colon being the most important one [1–5]. Enteric polymers are used for this purpose, as they are able to release the drug at a particular pH. The pH-sensitive copolymers, such as methacrylic acid/methyl methacrylate copolymers and Eudragit types L and S, dissolve in aqueous media at pH 6 and 7, respectively, which may be equivalent to drug release in the distal ileum [6]. Similarly, chitosan-based polyelectrolyte complexes have been employed as potential carrier materials in drug delivery systems [7]. Furthermore, a growing interest in polyelectrolyte complexes has led to the formulation and characterization of systems involving a variety of anionic and cationic polymers: Eudragit L 30 D-55 and gelatin [8], Eudragit L 100-Eudragit S 100 [9], Eudragit E-Eudragit L [10, 11], Eudragit E-sodium alginate [12], chitosan-alginate/chitosan-carrageenan (mainly kappa-carrageenan with low amounts of lambda-carrageenan) [13], chitosan-polygalacturonic acid [14], chitosan-carboxymethylcellulose [15], and chitosan-alginate [16]. Conventional drug delivery is unfavourable to special cases where drug targeting is applied, that is, when avoidance of gastric dissolution or targeting to the colon is desirable. Colon-targeted drug delivery differs
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