依巴斯汀滴丸剂的制备及溶出度考察

Preparation and Dissolution of Ebastine Dripping Pills

用熔融法制备依巴斯汀滴丸,利用Box-Behnken响应面法优化滴丸剂处方与制备工艺,并对预测结果进行验证。结果表明所得模型预测性较好,优化处方工艺为:药物与基质的比例为1∶3.4、基质中聚乙二醇(PEG)4000∶PEG6000的比例为1∶0.41、熔融温度为84℃。采用X射线粉末衍射法(XRD)及差示扫描量热法(DSC)对优化滴丸剂表征,并以市售片剂为对照考察自制滴丸的溶出性能。结果表明,优化后所制得的滴丸剂中药物以非晶态存在;5~30 min滴丸的溶出速度明显高于市售片剂,且滴丸的60 min溶出率为(89.0±4.8)%,片剂则为(78.0±4.7)%。

Ebastine is a new chloropiperidine antihistamine and shows a wide range of clinical applications. The main dosage forms of ebastine are tablets in the market. But commercial tablets normally have low dissolution, slow onset and other issues. The melting and dripping method was used to prepare ebastine dripping pills in order to improve the drug dissolution. Box-Behnken design-response surface method was adopted to optimize the formulation and preparation process of dripping pills and the predicted results were validated. The preferred formulation was as follows： the ratio of drug to matrix was 1 ： 3.4, the ratio of polyethylene glycol （PEG） 4000 to PEG 6000 in matrix was 1 ： 0.41, and the melting temperature was 84 ~C. The prepared dripping pills were characterized by X-ray powder diffraction （XRD） and differential scanning calorimetry （DSC）. The results showed that ebastine existed in non-crystalline form in the optimized dripping pills. The dissolution profiles of the optimized dripping pills in 0.1 mol/L hydrochloric acid were investigated with the commercial tablets as control. Compared with the commercial tablets, the dripping pills had the advantages such as rapid dissolution rate during 5--30 rain and higher dissolution amount in vitro. The dissolution amounts at 60 min of the dripping pills and the commercial tablets were （89.0：54.8） % and （78.0：54.7） %, respectively.