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

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 release 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/α-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 pellets 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 coating layer around the pellets. Delayed release system would be useful to deliver the drug to diseased sites and to achieve gradually the adequate drug release profile through the Gastrointestinal tract (GIT).