Stability of batanopride hydrochloride in aqueous solutions.
The degradation of batanopride hydrochloride, an investigational antiemetic drug, was studied in aqueous buffer solutions (pH 2-10; ionic strength, 0.5; 56 degrees 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.
Nassar
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Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Syracuse, NY 13221-4755.
House
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Agharkar
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D000932:Antiemetics / Q000737:chemistry*; D002021:Buffers; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008787:Metoclopramide / Q000031:analogs & derivatives* / Q000737:chemistry; D009994:Osmolar Concentration; D012996:Solutions; D014867:Water / Q000737:chemistry
D000932:Antiemetics; D002021:Buffers; D012996:Solutions; D014867:Water; C060190:batanopride; D008787:Metoclopramide