In vitro-in vivo relationships of several "immediate" release tablets containing a low permeability drug.

The objective of this work was to gain insight into the biopharmaceutical performance of four different but bioequivalent ranitidine hydrochloride tablet formulations. This analysis employed a recently described method1 to relate in vitro and in vivo data and aimed to facilitate an understanding of oral drug product performance. For each ranitidine formulation, dissolution was performed using the USP procedure. A four-way, single dose bioequivalence study (n = 14) was performed. The fraction of the total amount of dose absorbed at each plasma sample time was determined by the Wagner-Nelson method. Equation 1 (see below) was fitted to the in vitro vs. in vivo data. For all four formulations, this analysis suggests absorption was permeation-rate limited, where ranitidine exhibited a low permeation rate constant of 0.01/min.