SUSTAINED-RELEASE ALBUMIN MICROSPHERES CONTAINING ANTIBACTERIAL DRUGS - EFFECTS OF PREPARATION CONDITIONS ON KINETICS OF DRUG RELEASE

Albumin microspheres containing a variety of antibacterial drugs were prepared using bovine, egg and human albumin. The effects of such preparation conditions as denaturation time, denaturation temperature, agitation rate and concentration of cross-linking agent on the extent of drug incorporation and size of microspheres were determined. The release of chlorhexidine dihydrochloride and diacetate, metronidazole and cetylpyridinium chloride from various bovine, egg and human albumin microspheres were determined as a function of the pH of the release medium and with agitation of the release medium. The release rates from such microspheres were also studied in the presence of a proteolytic enzyme, pepsin, in the release medium. The kinetics of release from albumin microspheres containing the four drugs were compared to the theoretical models of Baker and Higuchi for diffusional release from spherical matrices. The kinetics of release of the drugs from albumin microspheres conformed to the Higuchi model. The effects of such release medium variables as agitation, pH and presence of enzymes, combined with electro micrographs of the microsphere surface and interior, suggest that release of drugs from microspheres occurs via leaching of the drug from spherical granular matrices. © 1990.