Stability of Batanopride Hydrochloride in Aqueous Solutions

Abstract

The degradation of batanopride hydrochloride, an investigational antiemetic drug, was studied in aqueous buffer solutions (pH 2–10; ionic strength, 0.5; 56 °C) in an attempt to improve drug stability for parenteral administration. Degradation occurs by two different mechanisms depending on the pH of the solution. In acidic media (pH 2–6), the predominant reaction was intramolecular cyclization followed by dehydration to form a 2,3-dimethylbenzofuran. There was no kinetic or analytical (high-performance liquid chromatography) evidence for the formation of an intermediate; therefore, the rate of dehydration must have been very rapid compared with the rate of cyclization. In alkaline media (pH 8–10), the primary route of degradation was cleavage of the C-O alkyl ether bond. In the intermediate pH range (pH 6–8), both reactions contributed to the overall degradation. Both degradation reactions followed apparent first-order kinetics. The pH-rate profile suggests that batanopride hydrochloride attains its optimal stability at pH 4.5–5.5. Citrate buffer was catalytic at pH 3 and 5, and phosphate buffer was catalytic at pH 8. No catalytic effect was observed for the borate buffer at pH 9–10.