Linear systems analysis and moment analysis in the evaluation of bacampicillin bioavailability from microcapsule suspensions

Linear systems analysis, i.e., numerical convolution/deconvolution, and moment analysis have been performed on data obtained from microcapsules containing the ampicillin prodrug bacampicillin hydrochloride. Three batches with different in vitrodissolution rates were scrutinized. From the results, it is concluded that numerical convolution/deconvolution is a valuable tool for predicting bacampicillin bioavailability. However, it must be emphasized that the selection of an appropriate time module is important for predicting an in vivoresponse that reflects the actual situation. This was verified by comparing the predicted plasma response values with the values obtained in a bioavailability study in healthy volunteers. A correlation between mean residence time in vivoand mean dissolution time in vitrowas also found which thus demonstrates the usefulness of moment analysis for obtaining an in vivo-in vitrorelationship. This relationship was compared to a correlation found between the mean dissolution time in vitroand the empirical maximum plasma concentration of bacampicillin.