Enhanced oral delivery of alendronate by sucrose fatty acids esters in rats and their absorption-enhancing mechanisms

Publication date: 30 December 2016 Source:International Journal of Pharmaceutics, Volume 515, Issues 1–2 Author(s): Tammam Alama, Hiroko Katayama, Sachiko Hirai, Shizuka Ono, Ayumi Kajiyama, Kosuke Kusamori, Hidemasa Katsumi, Toshiyasu Sakane, Akira Yamamoto Oral delivery is the most fascinating route for interminable drug remedy. However, the intestinal absorption of alendronate (ALN), a bisphosphonate drug after oral administration is very poor. Absorption enhancers, which help to achieve the efficiency-safety balance, are considered one of the most promising agents for the improvement the intestinal absorption of drugs. In the current study, we focused on using sucrose fatty acid esters (SEs) as promising absorption enhancers to enhance the intestinal absorption of alendronate using an in situ closed-loop method in rats. The intestinal absorption of alendronate was significantly enhanced in the presence of SEs, especially L-1695. In addition, no considerable increase was observed in the activity of lactate dehydrogenase (LDH) or in protein release from the intestinal epithelium in the presence of sugar esters at concentrations equivalent to or lower than 1.0% (w/v), suggesting that these compounds are safe. Furthermore, mechanistic studies revealed increased membrane fluidity and loosening of the tight junctions (TJs) might be the underlying mechanism by which SEs improve the intestinal intake of alendronate, via transcellular and paracellular routes, respecti...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research