Department of Pharmaceutics, Faculty of Pharmacy, El-Minia University, El-Minia Governate 61732, Egypt.
Int J Pharm. 2010 Sep 15;397(1-2):1-8. doi: 10.1016/j.ijpharm.2010.06.018. Epub 2010 Jun 19.
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. (13)C 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.
本研究旨在评估羧甲基-β-环糊精（CM-β-CyD）对法莫替丁（FMT）的水溶解度、化学稳定性和口服生物利用度以及苦味的潜在影响。我们考察了 CM-β-CyD 对 FMT 酸性降解的影响，并与磺丁基醚-β-环糊精（SBE-β-CyD）进行了比较。还评估了 CM-β-CyD 用于口腔崩解片（ODTs）的潜在用途，进行了体外和体内研究。此外，还进行了味觉感知研究。结果发现，CM-β-CyD 对酸性降解具有很强的稳定作用，而 SBE-β-CyD 则对 FMT 产生了奇特的不稳定作用。（13）C NMR 用于研究 FMT 与 2 种环糊精之间的相互作用模式。ODTs 的体内研究表明，与普通药物片剂相比，FMT-CM-β-CyD 片剂使 FMT 的 Cmax、AUC 和口服生物利用度显著增加。然而，Tmax 和 t1/2 没有显著差异。CM-β-CyD 络合似乎是一种可接受的策略，可增强 FMT 的口服生物利用度，因为它对药物的水溶解度和化学稳定性具有显著影响。此外，它对掩盖 FMT 的苦味有明显的作用。
