College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyongsan, South Korea.
Drug Dev Ind Pharm. 2013 Jun;39(6):901-8. doi: 10.3109/03639045.2012.717295. Epub 2012 Sep 10.
To develop a novel salt form of bepotastine with bioequivalent to the commericial bepostastine besilate, bepostastine salicylate was prepared and its physicochemical properties were investigated. Furthermore, the bepotastine salicylate-loaded tablet was prepared by the wet granulation method, and the dissolution and bioavailability in beagle dogs were evaluated compared to the bepotastine besilate-loaded commercial product. Bepotastine salicylate improved the solubility of bepotastine, and the extent of solubility improvement by salicylate form was similar to that by besilate form. However, this novel salt exhibited negligible hygroscopicity similar to besilate form, and showed slightly higher melting point than besilate form. It was stable in various pH solutions. Furthermore, the bepotastine salicylate-loaded tablet composed of bepotastine salicylate, microcrystalline cellulose, D-mannitol, povidone, sodium starch glycolate and sodium stearyl fumarate at the weight ratio of 9.63/60.97/38/3.6/6/1.8 showed similar dissolution to the bepotastine besilate-loaded commercial product in water, pH 1.2, pH 4.0 and pH 6.8 and was bioequivalent to the commercial product in beagle dogs. Thus, this bepotastine salicylate-loaded tablet would be a promising candidate with bioequivalence to the bepotastine besilate-loaded commercial product.
为开发与市售 besilate 盐形式生物等效的 bepotastine 新型盐形式，制备了 bepostastine 水杨酸盐，并研究了其理化性质。此外，通过湿法制粒法制备了载有 bepotastine 水杨酸盐的片剂，并与市售的 bepotastine besilate 载药产品进行了比较，评估了其在比格犬中的溶出度和生物利用度。Bepotastine 水杨酸盐提高了 bepotastine 的溶解度，水杨酸盐形式的溶解度改善程度与 besilate 形式相似。然而，这种新型盐表现出类似于 besilate 形式的可忽略的吸湿性，并且显示出比 besilate 形式略高的熔点。它在各种 pH 溶液中稳定。此外，由 bepotastine 水杨酸盐、微晶纤维素、D-甘露醇、聚维酮、交联羧甲基纤维素钠和富马酸钠按重量比 9.63/60.97/38/3.6/6/1.8 组成的载有 bepotastine 水杨酸盐的片剂在水中、pH1.2、pH4.0 和 pH6.8 中的溶出度与市售的载有 bepotastine besilate 的产品相似，并且在比格犬中与该产品生物等效。因此，这种载有 bepotastine 水杨酸盐的片剂可能是一种具有生物等效性的有前途的候选药物。
