Novel dabigatran etexilate hemisuccinate-loaded polycap: Physicochemical characterisation and in vivo evaluation in beagle dogs

Publication date: 15 June 2017 Source:International Journal of Pharmaceutics, Volume 525, Issue 1 Author(s): Jung Hyun Cho, Jin Cheul Kim, Hyung-Seo Kim, Dong Shik Kim, Kyeong Soo Kim, Yong Il Kim, Chul Soon Yong, Jong Oh Kim, Yu Seok Youn, Kyung Taek Oh, Jong Soo Woo, Han-Gon Choi The purpose of this study was to develop a novel dabigatran etexilate hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran etexilate base (DE) and succinic acid was less hygroscopic but less soluble than DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared employing the spiral jet-milling and spray-drying techniques, respectively. Among the formulations prepared, a micronized DEH prepared with the injection air at 1.5bar and the grinding air at 2bar, and a DEH-loaded solid dispersion prepared with 6g HPMC most improved the drug solubility, respectively. Moreover, the micronized DEH provided more increased drug solubility and dissolution compared with the solid dispersion, even though its drug solubility was still lower than that of DEM. Unlike the situation in other studies, the enhanced solubility and dissolution of DEH was more due to particle size reduction than to a change to the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug solubility than preparations with other surfactants. Among the organic acids investigated, only fumar...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research