基于增溶作用的阿苯达唑分散片研究

Study on albendazole dispersible tablets based on solubilization effect

为提高阿苯达唑的溶出性能,解决普通片剂可能造成患者吞咽困难等问题,基于增溶作用,研究探索制备阿苯达唑分散片的处方及工艺。首先,考察加入表面活性剂、用亲水性包合材料制成包合物对片剂溶出度的影响,筛选增加药物溶解度的方法;其次,采用单因素试验,以可压性、硬度、崩解时限、溶出度为考察指标,对黏合剂、崩解剂、增溶剂、润滑剂等进行筛选,通过正交试验优化处方及工艺;最后,按最优处方及工艺制备3批阿苯达唑分散片,进行质量评价,采用紫外分光光度法测定其含量和溶出度。结果表明,联合使用十二烷基硫酸钠和聚山梨酯80可增加阿苯达唑在水中的溶解度;阿苯达唑分散片的优选处方如下:十二烷基硫酸钠用量为3%(质量分数,下同),PVPP用量为16%(内外加比例为1∶1),聚山梨酯80用量为3%,羟丙基甲基纤维素溶液用量为3%,硬脂酸镁用量为1%,采用湿法制粒压片;制备的不同批次阿苯达唑分散片在122 s内完全崩解,药物在45 min时累积溶出度均大于80%,符合2020年版《中华人民共和国药典》要求。所研制的阿苯达唑分散片处方合理,制备工艺可行,体外质量良好,为改善生物药剂学分类系统(BCS)Ⅱ类药物口服制剂的生物利用度提供了研究思路和理论依据。

In order to improve the dissolution properties of albendazole and solve the problem of dysphagia caused by conventional tablets in patients, the prescription and preparation process of albendazole dispersible tablets were explored based on the solubilization effect.The effects of adding surfactants and preparing inclusion compounds on dissolution were investigated to screen the method of increasing the solubility of albendazole.Adhesives, disintegrants, solubilizers, and lubricants were screened by single factor experiment with compressibility, hardness, disintegrating time, and dissolution as indicators.The formulation and preparation process of albendazole dispersible tablets were optimized by orthogonal test.Three batches of albendazole dispersible tablets were prepared by the optimal prescription and process, the qualities were evaluated in vitro,and the content and dissolution were measured by UV-spectrophotometry.The results show that adding mixed surfactants of sodium dodecyl sulfate(SDS) and Tween 80 can assist dissolution of albendazole in water.The optimal prescription is as follows: 3% of SDS,16% of PVPP(with an internal and external ratio of 1∶1),3% of Tween 80,3% of HPMC and 1% of Magnesium Stearate.The albendazole dispersible tablets were prepared with wet granulation.Different batches of albendazole dispersible tablets completely disintegrated within 122 s, the accumulated dissolution of albendazole dispersible tablets within 45 minutes was more than 80%,which met the requirements of Pharmacopoeia of the People’s Republic of China(2020).The formulation of albendazole dispersible tablets is reasonable, the preparation process is feasible and the quality is good in vitro,which provides research ideas and a theoretical basis for improving the bioavailability of oral dosage forms of biopharmaceutical classification system(BCS) class Ⅱ compounds.