Design and characterization of mesalamine rectal drug delivery system to treat inflammatory bowel disease

Abstract

quotIntroduction: Mesalamine is a used to treat inflammatory bowel disease and is given orally at a high dose of 400 800 mg per day. This leads to non-specific absorption causing a plethora of side effects. As the effect is needed only in the gastrointestinal tract a local drug delivery system releasing in a controlled fashion could prove to be more effective. Thus, the present work involves forming mucoadhesive pellets which were then loaded into a suppository to be administered via the rectal route for local and controlled release. newline newlineMethods: Extrusion spheronization method was used to prepare pellets containing Eudragit RLPO as the release retardant, carrageenan as a mucoadhesive polymer and other excipients. The process was optimized using factorial design and the pellets of the optimized batch were loaded into a cocoa butter base suppository as well as a directly compressed rectal tablet. A full spectrum of in-vitro evaluation was performed on the pellets, pellets-loaded suppositories, and the pellets-loaded rectal tablets. newline newlineResults: The optimized batch of pellets had a mucoadhesion strength of 0.143 N, a swelling index of 50.50 %, and 44 % and 75 % drug was release from them at the end of 6 and 15 hours respectively. The suppositories had a macro melting range of 36.8 ± 0.4 °C and a micro melting range of 35.7 ± 0.7 °C. The suppositories took 6.2 ± 0.03 mins to soften at 37 ± 0.8 °C. They showed an acceptable weight variation (2.89 ± 0.03 g), disintegration time (8.6 ± 1.5 min), hardness (4.35 ± 0.65 kg/cm3), and swelling index (50.70 ± 1.15 %). The in vitro release profile of the drug from the pellets-loaded suppositories and MSL-loaded pellets is almost similar indicating that the base did not affect the rate of drug release.The tablets showed acceptable uniformity of weight, hardness, and disintegration time. But the other parameters such as friability, swelling index, ex vivo mucoadhesion strength, and ex vivo residence time was found to be suboptimal. A concurrent effect was observed in the in vitro