Acid–base chemistry of omeprazole in aqueous solutions Original Research Article

Omeprazole is a potent anti-acid drug. Its absorption and mode of action are closely related to its prototropic behavior. In the present study, omeprazole samples from different sources and in different forms were studied spectrophotometrically to obtain pKa values. In the neutral to alkaline pH region, two consistent pKa values of 7.1 and 14.7 were obtained from various samples. The assignment of these pKa values was realized by comparison with the prototropic properties of N(1)-methylated omeprazole substituted on the nitrogen at the 1-position of the benzimidazole ring, which was found to have a pKa of 7.5. The omeprazole pKa of 14.7 is assigned to the dissociation of the hydrogen from the 1-position of the benzimidazole ring and the pKa of 7.1 is assigned to the dissociation from the protonated pyridine nitrogen of omeprazole. The results presented are at variance with those of earlier work.