Design and Characterization of Mucoadhesive Controlled Release Multparticulate Systems of Ketoprofen to Target the Small Intestine

Abstract

Ketoprofen is a non-steroidal anti-inflammatory drug and is used in the treatment of rheumatoid arthritis, ankylosing spondilitis and osteoarthritis. Currently it is used as tablets and capsules for immediate or sustained release of drug. One of the major side effects of ketoprofen from the currently available dosage form is gastritis due to the release of the drug in the stomach. Ketoprofen, a highly soluble in alkaline pH and so its release in the intestine will facilitate improved bioavailability and freedom from gastritis. Taking into account the above factors the present study was aimed to develop dosage forms that will release the drug in the intestine with prolonged action. Microbeads and microsponges were the two approaches selected in the present study to meet the above objectives. Microbeads were prepared using sodium alginate, pectin, xanthan gum as polymers and calcium chloride and zine chloride as cross linking agents in varying proportions and evaluated for physiochemical and in vitro release characteristics. SEM analysis indicates that the morphology of beads was found to be affected by the concentration or type of counter ion and not by concentration of the polymers. The stirring speed did not influence the particle size and entrapment efficiency. The release rate of drug from microsponges was independent of PVA concentration and stirring speed. From the release characteristics, it was observed that microsponges prepared with Eudragit, Carbopol, Chitosan are more desirable for controlled delivery than microbeads. Both microbeads and microsponges followed zero order release kinetics and the drug release was through polymer relaxation or erosion. Besides, microsponges were more mucoadhesive than microbeads and hence controlled release is better from microsponges due to increased residence time in the intestine. The results of the in vive study indicate that microsponges provided controlled release of the ketoprofen for 24 h compared to ketoprofen powder. newline