双硫仑片剂的制备及体外溶出度研究

Preparation and in vitro dissolution of Disulfiram Tablets

目的对双硫仑片剂进行处方和工艺优化研究,并以原研制剂双硫仑片剂(ANTABUSE)为参比制剂,对自制片剂进行体外溶出度考察。方法采用干法研磨技术增大药物的溶解度和溶出速度,采用湿法制粒压片法制备双硫仑片剂,以双硫仑和无水乳糖比例、低取代羟丙基纤维素和羧甲基淀粉钠的比例以及薄膜衣增质量作为考察指标,控制研磨、制粒和总混参数,进行处方及工艺优化,并以体外溶出度为考察指标。结果最佳制备工艺为:双硫仑与无水乳糖比例为6∶4,低取代羟丙基纤维素和羧甲基淀粉钠的用量比为1∶2,薄膜衣增质量为3%,混合物研磨12 h,混合制粒时间为10 min。自制片剂与原研双硫仑片剂体外溶出曲线具有相似性。结论双硫仑片剂的处方工艺合理,得到的自制片的体外溶出度良好,说明该工艺适用于双硫仑包衣片剂的制备。

Objective To study the optimal prescription and preparation process of Disulfiram Tablets,to select the original preparation agent,and to observe the in vitro dissolution when ANTABUSE was used as a reference preparation.Methods The dry grinding method was used to increase the solubility and dissolution rate of the drug.The Disulfiram Tablets were prepared by wet granulation tableting method.The ratio of disulfiram to anhydrous lactose,low substitution of hydroxypropyl cellulose and carboxymethyl starch sodium and weight gain of film clothing along with the grinding,granulation,and total mixing,were used as inspection indicators to control the parameters and to optimize the prescriptions and preparation.The dissolution was used as evaluation indicator.Results The optimal preparation conditions were as follows:the ratio of disulfiram to anhydrous lactose was 6∶4,the ratio of low-substituted hydroxypropyl cellulose to sodium carboxymethyl starch was 1∶2,the weight gain of film clothes was 3%,the mixture was ground for 12 h,the mixing granulation time was 10 min.The in vitro dissolution of the obtained tablets was similar to that of the original preparation.Conclusion The formulation process of disulfiram-coated tablets was reasonable,and the in vitro dissolution rate of the self-made tablets was good,indicating that this process is suitable for the preparation of disulfiram-coated tablets.