The current requirement of the Mexican Authorities to demonstrate the interchangeability 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 degrees C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean+/-SEM) were: Cmax 528.85+/-25.34 and 563.03+/-33.25 ng/ml, tmax 2.76+/-0.19 and 2.79+/-0.18 h, and AUC12 h 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 Cmax and AUC12 h 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.
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