DRUG-RELEASE BEHAVIOR IN GASTROINTESTINAL-TRACT OF BEAGLE DOGS FROM MULTIPLE-UNIT TYPE RATE-CONTROLLED OR TIME-CONTROLLED RELEASE PREPARATIONS COATED WITH INSOLUBLE POLYMER-BASED FILM

Drug release behaviors from two multiple unit types of controlled rele ase systems were observed in the gastrointestinal (GI) tract of beagle dogs. Factors affecting the in vivo drug release are discussed. The i n vivo drug release behaviors were directly predicted by measuring the residual amount of drugs in preparations recovered from the GLI tract after oral administration. Theophylline (TP) and propranolol hydrochl oride (PPL), which have markedly different solubility, were used as mo del drugs. A rate-controlled release preparation (porous ethylcellulos e film-coated beads) and a time-controlled release preparation (SRS; s igmoidal release system) were examined, Although in vivo TP release fr om the rate-controlled release beads agreed considerably with in vitro release in the early stages, it was reduced by a lack of fluid in the lower region of the GI tract and the lower water-solubility of the dr ug. On the other hand, PPL release in vivo was in accord with the in v itro release, and the drug was released almost completely from the bea ds in the GI tract. In the case of PPL-SRS, although the in vivo relea se rate was slightly lower than that in vitro, sigmoidal drug release was also observed in the GI tract. TP was not released entirely from t he SRS or the porous ethylcellulose film-coated beads in the GI tract. In conclusion, with respect to drug release from controlled release p reparations coated with insoluble polymer based-film coating, a good i n vitro/in vivo correlation was observed in the early stages of drug r elease, irrespective of drug properties, but solubility of the drugs w as found to be an important factor that affected the drug release in t he lower site of GI tract of dogs.