Inhibition of Gastric H⁺,K⁺-ATPase Activity <i>in Vitro</i> by Dissolution Media of Original Brand-Name and Generic Tablets of Lansoprazole, a Proton Pump Inhibitor

Abstract

To investigate the inhibitory effect of a commercial proton pump inhibitor (lansoprazole) on the gastric proton pump H,K-ATPase in vitro, we used orally disintegrating (OD) tablets including original brand-name and generic tablets. In the course of the development of generic products, dissolution and clinical tests are necessary to ensure their bioequivalence to the original brand-name products; by contrast, there is almost no opportunity to demonstrate their activity in vitro. This study initially compared the similarity of the dissolution of test generic tablets with that of the original brand-name tablets. The dissolution tests for 15 and 30-mg lansoprazole tablets found their dissolution properties were similar. Subsequently, the dissolution media were sampled and then their effects on the H,K-ATPase activity were measured using tubulovesicles prepared from the gastric mucosa of hogs. We confirmed that the inhibitory effects of the generic tablets on H,K-ATPase activity were consistent with those of the original brand-name tablets. Furthermore, lansoprazole contents in each tablet estimated from their inhibitory effects were in good agreement with their active pharmaceutical ingredient content. To our knowledge, this is the first technical report to compare the in vitro biochemical activity of lansoprazole OD tablets between the original brand-name and generic commercial products.

Synthesis and crystal structure of trifluoromethyl-containing bendamustine hydrochloride

“…23 The difference between these drugs is that lansoprazole contains a trifluoromethyl group, which can significantly improve drug stability and help to enhance its inhibitory effect on gastric acid secretion mechanism, thereby significantly improving the effect of clinical disease control. 24,25 In this context, in view of the importance of bendamustine hydrochloride as an anti-tumor agent as well as the positive effect of CF 3 in organic molecules, it would be meaningful to introduce a CF 3 group on bendamustine hydrochloride (Figure 1(b)). In our continuing efforts for preparing important bioactive compounds,26 herein, Synthesis and crystal structure of trifluoromethyl-containing bendamustine hydrochloride using 2,4-dinitrochlorobenzene as a raw material, trifluoromethyl-containing bendamustine hydrochloride has been designed and synthesized by a series of organic synthesis steps including substitution, selective reduction, N-acylation, cyclization, esterification, nitro-reduction, N-dihydroxyethylation, chlorination, and acid-catalyzed hydrolysis (Scheme 1).…”