Formulation and Optimization of Osmotically Controlled, Microbially Triggered Colon Targeted System Using Face Centered Central Composite Design

The purpose of present investigation was to achieve successful delivery especially to colon using microbially triggered, osmotically controlled approach. Prednisolone was chosen model drug for treatment of inflammatory bowel disease (IBD). Prednisolone-β-cyclodextrin complex were prepared and phase solubility study was carried out. Cellulose acetate solution containing chitosan was used to prepare semi-permeable. Face centered central composite design was employed to study the effect on independent variables (concentration of sodium chloride, polyethylene glycol, and chitosan), % cumulative release and disintegration time. Both independent variables, the proportion of chitosan (X1) and proportion of NaCl and PEG (X2) had an influence on the % drug release in both the media (buffers and buffer with rat ceacal content). Formulations were evaluated for their Preformulation parameters and found within the specified limit. Formulation code F8 and S8 were the optimized batches with an in vitro release of 83.77 and 99.13 % respectively. The formulations containing PEG was found to be a promising drug delivery system better release kinetics. INTRODUCTION: Oral drug delivery is the most desirable and preferred method of administering therapeutic agents for their systemic effects. Oral drug delivery system can be classified into three categories: Immediate-release (IR) preparation, Controlled-release (CR) preparation and Targeted release preparation or site specific drug delivery system that requires spatial placement of drug delivery device at a desired site within the GI tract . Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastro intestinal tract presents several formidable barriers to drug delivery. It has serious drawback in conditions where localized delivery of the drug in the colon is required or in the condition where a drug needs to be protected from hostile environment of the upper region of the gastrointestinal tract . Colon specific drug delivery system should be capable of protecting the drug en route to the colon i.e. drug release and absorption should not occur in the stomach as well as in the small intestine, but the drug only released and absorbed once the system reaches to the colon . Colonic delivery offers numerous therapeutic advantages like drugs, which are destroyed by the stomach acid and metabolized by pancreatic enzymes are minimally effected in the colon . Colon targeted drug delivery systems have been gaining significant attention not just for providing more effective therapy to colon related disease, but also as a potential approach for systemic delivery of therapeutic proteins and peptide drugs. Colon is also a potential site for treatment of disease sensitive to circadian rhythms such as asthma, angina, arthritis, etc 5, .