title: Pharmaceutical design of a novel colon-targeted delivery system using two-layer-coated tablets of three different pharmaceutical formulations, supported by clinical evidence in humans.
abstract: Drug delivery systems to the colon are being actively investigated in order to develop oral preparations of peptides and treat local colonic diseases. However, it is difficult to ensure that an oral preparation disintegrates specifically in the human colon. To make a colonic delivery system practical for medical use, in vitro testing methods need to be established in order to determine the specifications of the preparations. To achieve this objective, three pharmaceutical preparations, designed to have different tablet disintegration times, were used to examine three buffers in seven combinations intended to simulate pH changes in the stomach, small intestine, and colon of humans. To validate the in vitro methodology, furthermore, the fate of all the formulations was examined in the gastrointestinal (GI) tract of healthy volunteers. A three-way crossover trial by scintigraphy revealed that the three formulations--in spite of presenting different in vitro tablet disintegration profiles--have comparable transit profiles and excellent colon-targeting properties in the human gastrointestinal tract regardless of gender and age. These facts strongly suggest that this novel delivery system may be useful for the delivery of drugs to the human colon.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Kawachi-gun, Tochigi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tanida
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yoshinaga
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.forename: D J
authors.initials: DJ
authors.lastname: Ball
authors.forename: I R
authors.initials: IR
authors.lastname: Wilding
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D013608:Tablets, Enteric-Coated
chemical_list: D004364:Pharmaceutical Preparations; D013608:Tablets, Enteric-Coated