Development of time-, pH-, and enzyme-controlled colonic drug delivery using spray-dried chitosan acetate and hydroxypropyl methylcellulose.

A colonic drug delivery with a new concept based on a combination of time-, pH-, and enzyme-controlled system was developed. Spray-dried chitosan acetate (CSA) prepared from low molecular weight chitosan was characterized. A combination of CSA and hydroxypropyl methylcellulose (HPMC) was used as new compression-coats for 5-aminosalicylic acid (5-ASA) tablets. Factors affecting in-vitro drug release, i.e. % weight ratio of coating polymers, enzyme activity, pH of media, and excipients in core tablets, were evaluated. The tablets compression-coated with HPMC:CSA at 60:40 and 50:50% weight ratio providing lag times about 5-6h were able to pass through the stomach (stage I, 0.1N HCl) and small intestine (stage II, pH 6.8, Tris-HCl). The delayed release was time- and pH-controlled owing to the swelling with gradual dissolving of CSA and HPMC in 0.1N HCl and the less solubility of CSA at higher pH. After reaching the colon (stage III, pH 5.0, acetate buffer), the dissolution of CSA at low pH triggered the drug release over 90% within 14h. Furthermore, the degradation of CSA by beta-glucosidase in the colonic fluid enhanced the drug release while adding the disintegrant or the osmotic agent in the core tablets would affect the drug release.