Development and Human in vivo Evaluation of a Colonic Drug Delivery System
Walid A. Habib a and Adel Sakr b CIMA Labs.a , Brooklyn Park, Minnesota (USA), and Industrial Pharmacy Graduate Program, College of Pharmacy, University of Cincinnati Medical Center b , Cincinnati, Ohio (USA)
The objective of this study was to develop and evaluate a colonic drug delivery system for the polypeptide antimicrobial agent nisin (CAS 1414-45-5). Being a polypeptide, nisin is susceptible to degradation in the small intestine. Nisin was formulated into 100 mg tablets which were coated in the Wurster Fluid Bed Apparatus using methacrylic acid copolymer USP/NF type C, commercially known as EudragitÃ¢ L30D-55, at various coating thicknesses. The effects of Eudragit on the in vitro and in vivo release of nisin were studied. It was found that the coated tablets resisted disintegration in 0.1 N HCl for 2 h and a linear relationship was established between coating thickness and/or percent weight gain, and the time to beginning of disintegration. Tablets containing samarium oxide ( 152Sm) were neutron activated ( 153Sm) and their disintegration was tested in human volunteers using gamma scintigraphy. An in vivo/in vitro correlation between coating thickness/weight and the disintegration of the coating in humans was found. A coating thickness of 0.381 mm was found to be optimal for targeting nisin to the colon.
Key words Drug targeting Â· Enteric coating Â· Methacrylic acid copolymer Â· Nisin Â· Polypeptides
Â© ECV- Editio Cantor Verlag (Germany) 1999
pharmind 1999, Nr. 12, Seite 1145