EFFECT OF SODIUM ACID PYROPHOSPHATE ON RANITIDINE BIOAVAILABILITY ANDGASTROINTESTINAL TRANSIT-TIME

During development of a ranitidine effervescent oral solution dosage f orm, a marked decrease was observed in the extent of ranitidine absorp tion relative to the conventional oral tablet. Two studies were conduc ted in healthy volunteers to confirm the involvement of an excipient, SAPP (sodium acid pyrophosphate), and the mechanism of interaction, al tered gastrointestinal transit. The first study (n = 12) involved sing le-dose crossover comparisons of (A) 150 mg ranitidine with 1132 mg SA PP versus (B) 150 mg ranitidine and (C) 150 mg ranitidine with all the effervescent tablet excipients except SAPP versus (D) a 150-mg raniti dine effervescent tablet, all administered as oral solutions. Serum ra nitidine AUC, C(max), and t(max) were compared using two one-sided t t est 90% confidence intervals (CI). Comparing treatments A to B and D t o C, all 90% CI were below the 80-120% range, indicating significantly less extensive ranitidine absorption (54% based on AUC) from the oral solutions containing SAPP. The second study (n = 12) was a single-dos e crossover comparing 50 muCi (InCl)-In-111 solutions with and without 1132 mg SAPP. Gastrointestinal transit times, determined by scintigra phic imaging, were compared between treatments. Gastric emptying time was unchanged, but small intestinal transit time was decreased to 56% in the presence of SAPP. More rapid small intestinal transit associate d with an excipient of a solution dosage form apparently resulted in a decreased extent of ranitidine absorption. This observation contradic ts the conventional wisdom that oral solutions are unlikely to fall sh ort of bioequivalence relative to solid oral formulations.