Combination of Time-Dependent and pH-Dependent System for Intestinal Delivery of 4-Aminosalicylic Acid Based Pellets

Abstract

A lipidic matrix pellet based on Gelucire ® was developed for delivering drug to both distal small intestine and proximal colon. Sodium Dodecyl Sulfate (SDS) was used to extend the time of the mixture in solidification. Alpha- Cyclodextrin a cyclic oligosaccharide was added to the mixture to prevent drug degradation and provide appropriate re- lease profile. Gelucire 50/02 matrix pellets were coated with an outer layer of pH-dependent polymer: Eudragit FS30D. Three formulations were retained as good to have sustained release profiles 40/45/15, 35/50/15 and 30/55/15 (Gelucire/4- ASA/� -CD). These mixtures are convenient to obtain a solid pellet with good friability rate close to 1%. Dissolution test was conducted for uncoated pellets and release rates were between 76.82±0.12% and 83.35±0.7% for formulations with SDS 0.25%, between 76.1±0.83% and 83.7±0.7% for formulations with SDS 0.5% and between 67.86±0.48% and 92.44±0.3% for formulations with SDS 0.75%. Furthermore release profile of 4-aminosalicylic acid (4-ASA) coated pel- lets was studied in a phosphate buffer after a simulated gastric for 2 hours in pH 1.5 media. For 2 hours no significant drug release was detected at this pH (<3%). There was a delayed release of 4-aminosalicylic acid (4-ASA) for 2 hours and no lag time at pH 7.5. Extended release was observed in this later condition for 5hours to reach release rate close to 90%. Scanning electron micrograph (SEM) pictures of the coated and uncoated pellets showed a relative uniformity of the coat- ing layer around the pellets.