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

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• 作者：Fatma M. Mady ; Ahmed E. Abou-Taleb ; Khaled A. Khaled ; Keishi Yamasaki ; Daisuke Iohara ; Kazuaki Taguchi ; Makoto Anraku ; Fumitoshi Hirayama ; Kaneto Uekama ; Masaki Otagiri
• 关键词：Famotidine ; Carboxymethyl-β ; -CyD ; Chemical stability ; Oral bioavailability ; Masking the bitter taste and oral disintegrating tablets
• 刊名：International Journal of Pharmaceutics
• 出版年：2010
• 出版时间：15 September 2010
• 年：2010
• 卷：397
• 期：1-2
• 页码：1-8
• 全文大小：288 K

文摘

The objective of the present study was to evaluate the potential influence of carboxymethyl-β-cyclodextrin (CM-β-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-β-CyD on the acidic degradation of FMT compared with that for sulfobutyl-ether-β-cyclodextrin (SBE-β-CyD). The potential use of CM-β-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-β-CyD was observed against the acidic degradation, in sharp contrast to SBE-β-CyD which induced a weird destabilizing effect on FMT. ¹³C 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-β-CyD tablets, compared with plain drug tablets. However, no significant difference in T_max and t_1/2 was observed. CM-β-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.