坎地沙坦酯片的制备及初步稳定性研究

Preparation and Preliminary Stability of Candesartan Cilexetil Tablets

目的:制备坎地沙坦酯片并优化处方,并对其进行初步稳定性考察。方法:采用Box-Behnken试验设计,以填充剂配比(X1)、崩解剂(X2,%)和润滑剂(X3,%)用量为影响因素,以片重差异(Y1,%)、脆碎度(Y2,%)、崩解时限(Y3,min)、坎地沙坦酯溶出度(Y4,%)为片剂考察指标,得到最优处方;采用f2相似因子法评价自制制剂和参比制剂在溶出介质中的体外溶出行为。通过高温、高湿、光照试验初步考察制剂稳定性。结果:坎地沙坦酯片的最优处方组成为:填充剂一水乳糖与预交化淀粉比例为7∶1、崩解剂交联羧甲基纤维素钠占片重为5.5%,润滑剂硬脂酸镁占片重为0.5%。自制片剂和参比制剂在4种溶出介质中的累积溶出度相似因子f2分别为60.62,73.34,66.95,68.60。结论:制备的坎地沙坦酯片各项指标均符合规定,工艺稳定可靠。

Objective： To prepare and optimize candesartan cilexetil tablets,and study the stability preliminarily. Methods： The formula was optimized by Box-Behnken experiment design,the ratio of lactose to pregelatinized starch（ X1）,the amount of disintegrant（ X2,%） and the amount of lubricant（ X3,%） were selected as the independent variables,and weight difference（ Y1,%）,friability（ Y2,%）,disintegration time（ Y3,%） and candesartan cilexetil dissolution（ Y4,%） were the dependent variables. The release rate of candesartan cilexetil tablets and the reference tablets were compared by similarity factor（ f2value）. Preliminary stability was studied by high-temperature test,high-humidity test and illumination test. Results： The optimal formula of the tablets was as follows： the ratio of lactose to pregelatinized starch was 7∶ 1,the amount of disintegrant was 5. 5%,and the amount of lubricant was 0. 5%. The f2 for the candesartan cilexetil tablets and the reference tablets in different dissolution meda was 60. 62,73. 34,66. 95 and 68. 60,respectively. Conclusion： The formula design is reasonable,the preparation process is feasible and the quality can be controlled.