Takao Mizumoto

Influence of physical factors in gastrointestinal tract on acetaminophen release from controlled-release tablets in fasted dogs

Abstract Four types of controlled-release (CR) acetaminophen (AAP) tablets, namely A, B, C and D, were prepared to investigate the influence of physical factors in the gastrointestinal (GI) tract on AAP release in fasted dogs. CR-A was designed as a completely resistant formulation to mechanical destructive force but to show an agitation speed-dependent dissolution rate. CR-B, CR-C and CR-D were designed to have different wet strengths but to show similar dissolution rates. The absorption profiles of the four CR forms in dogs showed biphasic patterns, with phase change about 2 h after oral dosing. The first phase of the absorption profile of CR-A and in vivo release directly observed were close to its in vitro profiles at a speed of 25–50 revs./min, indicating that agitation intensity in the dog GI tract may be relatively low. The first phase of the absorption profiles of the CR-B, CR-C and CR-D differed from each other, despite the fact that dissolution rates in vitro were similar. The tablet with low wet strength showed a faster absorption rate, indicating that it would be destructed by GI mechanical forces. Furthermore, absorption during the second phase was extremely low for all CR tablets. We confirmed on necroscopy that the suppression of drug absorption in the second phase was caused by the termination of AAP release from the tablets in the colon. These results will be useful in evaluating the in vivo performance of CR tablets in fasted dogs.

Evaluating tamsulosin hydrochloride-released microparticles prepared using single-step matrix coating.

The objective of the present study was to determine the optimum composition for sustained-release of tamsulosin hydrochloride from microparticles intended for orally disintegrating tablets. Microparticles were prepared from an aqueous ethylcellulose dispersion (Aquacoa®), and an aqueous copolymer based on ethyl acrylate and methyl methacrylate dispersion (Eudragit®) NE30D), with microcrystalline cellulose as core particles with a fluidized bed coating process. Prepared microparticles were about 200 μm diameter and spherical. The microparticles were evaluated for in vitro drug release and in vivo absorption to assess bioequivalence in a commercial product, Harnal® pellets. The optimum ratio of Aquacoat® and Eudragit® NE30D in the matrix was 9:1. We observed similar drug release profiles in microparticles and Harnal® pellets. Higuchi model analysis of the in vitro drug release from microparticles was linear up to 80% release, typical of Fickian diffusion sustained-release profile. The in vivo absorption properties from microparticles were comparable to Harnal® pellets, and there was a linear relationship between in vitro drug release and in vivo drug release. In conclusion, this development produces microparticles in single-step coating, that provided a sustained-release of tamsulosin hydrochloride comparable to Harnal® pellets.