title: Use of the BioDis to generate a physiologically relevant IVIVC.
abstract: In the last decades there has been continual interest in site-specific delivery to the colon. Recently, new types of site-specific delivery formulations have been developed for the treatment of ulcerative colitis and other colon related diseases. The aim of the present study was to establish a physiologically relevant IVIVC for two prototypes using a prospective in vitro study. Caffeine, a drug being absorbed along the entire gastrointestinal tract, was selected as a model drug. USP apparatus 3, the BioDis, was used for all experiments and the passage through the gastrointestinal tract was simulated with a physiologically based pH-gradient. Subsequently, the fraction of drug released in vitro was compared with the fraction of drug released in vivo, which was determined in humans in a separate study. Results indicated that the BioDis method is very useful in terms of predicting the site/timing and extent of drug release from the prototypes, since an a priori IVIVC could be established. Moreover, from the results generated in the present study, it is obvious that novel pH- and time-based multi-unit formulations would improve selectivity of drug delivery to the distal ileum and the colon and therefore might be very helpful in the treatment of colonic diseases.
authors.affiliation: Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, 9 Max von Laue Street, Frankfurt, Main 60438, Germany. Sandra.Klein@em.uni-frankfurt.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Klein
authors.forename: Markus W
authors.initials: MW
authors.lastname: Rudolph
authors.forename: Brigitte
authors.initials: B
authors.lastname: Skalsky
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Petereit
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D001682:Biological Availability; D002110:Caffeine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005215:Fasting / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D011109:Polymethacrylic Acids / Q000737:chemistry
chemical_list: D000277:Adjuvants, Pharmaceutic; D000697:Central Nervous System Stimulants; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D002110:Caffeine