Comparative bioavailability of two oral formulations of ranitidine

The current requirement of the Mexican Authorities to demonstrate the interchange-ability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty-five female volunteers received 150 mg ranitidine (Azantac® or Midaven®) under fasting conditions in two separate sessions using a cross-over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at -80°C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean ± SEM) were: C_max 528.85±25.34 and 563.03 ± 33.25 ng/ml, t_max 2.76 ± 0.19 and 2.79 ± 0.18h, and AUC_12h 2694.94 ± 99.50 and 2648.51 ± 133.38 ng.h/ml, for Azantac® or Midaven®, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%-116.2% and 90.7%-105.1% for C_max and AUC_12h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations.