Biopharmaceutical Evaluation of Sustained-Release Ethylcellulose Microcapsules Containing Cefadroxil and Cephradine Using Beagle Dogs

抄録

Two cephem antibiotics, cefadroxil and cephradine, were microencapsulated with ethyl cellulose using a solvent evaporation process in liquid paraffin containing sorbitan tristearate as a dispersing agent. These products were administered to beagle dogs and biopharmaceutical evaluations were made of the sustained-release effect. First, Vallner's method was employed for the assessment of the sustained-release ethylcellulose microcapsules. The controlled release effectiveness was close to 0.8 for ethylcellulose microcapsules containing 70% cefadroxil and 60% cephradine. Second, assessments were made using pharmacokinetic parameters based on a model allowing for the gastric-emptying and intestinal transit rates of the drug itself and the solid state drug contained in the microcapsules using nonlinear least-squares regression. The results obtained showed that transfer of the rate-limiting step to the release process from the absorption process could be observed in microcapsules containing 70% cefadroxil but not in the case of microcapsules containing 60% cephradine. The release rates calculated on the basis of the above model correlated well with the release rate in dissolution tests at pH 6.8. Finally, a new nomogram was introduced for the design of sustained-release formulaitons in the future.