Evaluation of carboxymethyl-β-cyclodextrin with acid function: Improvement of chemical stability, oral bioavailability and bitter taste of famotidine

The objective of the present study was to evaluate the potential influence of carboxymethyl-beta-cyclodextrin (CM-beta-CyD) on the aqueous solubility, chemical stability and oral bioavailability of famotidine (FMT) as well as on its bitter taste. We examined the effect of the CM-beta-CyD on the acidic degradation of FMT compared with that for sulfobutyl-ether-beta-cyclodextrin (SBE-beta-CyD). The potential use of CM-beta-CyD for orally disintegrating tablets (ODTs) was evaluated in vitro and in vivo. A taste perception study was also carried out. A strong stabilizing influence of CM-beta-CyD was observed against the acidic degradation, in sharp contrast to SBE-beta-CyD which induced a weird destabilizing effect on FMT. C-13 NMR was used to investigate the interaction mode between FMT and the 2 CyDs. In vivo study of ODTs indicated a significant increase in C-max, AUC and oral bioavailability in the case of FMT-CM-beta-CyD tablets, compared with plain drug tablets. However, no significant difference in T-max and t(1/2) was observed. CM-beta-CyD complexation appears to be an acceptable strategy for enhancing the oral bioavailability of FMT owing to its dramatic effect on the aqueous solubility and chemical stability of the drug. In addition, it has a pronounced effect on masking the bitter taste of FMT. (C) 2010 Elsevier B.V. All rights reserved.