硝苯地平控释片制备及其体内研究

Preparation and in Vivo Study of Nifedipine Controlled-Release Tablets

目的:研究一种新型的硝苯地平控释片的处方工艺,使用聚羧甲基淀粉钠作为膨胀材料,聚维酮与共聚维酮作为载药材料,制备双层渗透泵型控释片,并进行工艺放大及体内等效性研究。方法:采用单因素控制变量法逐一考察可能影响硝苯地平控释片的溶出曲线的因素,如膨胀剂种类、推进层中羧甲基淀粉钠和共聚维酮用量、半渗透膜包衣增重、激光打孔孔径等,优选所得处方进行工艺放大及体内等效性研究。结果:羧甲基淀粉钠作为膨胀材料,聚维酮与共聚维酮作为载药材料,卡波姆作为缓释材料;处方所制得样品相似因子(f_(2)值)大于50,溶出曲线与参比制剂相似;工艺放大结果表明,自研控释片工艺重现性好,f_(2)值均大于50,适合大规模生产;体内等效性研究表明,C_(max)、AUC_(0-t)和AUC_(0-∞)受试制剂与参比制剂几何均数比值及其90%置信区间分别为107.58%(95.20%,121.57%)、99.33%(86.27%,114.35%)、99.43%(87.89%,112.49%),在可接受范围内。结论:自研硝苯地平控释片处方合理,制备工艺可行,自制制剂与参比制剂具有生物等效性。

Objective:To study a new formulation and process of nifedipine controlled-release tablets,use povidone/copovidone as the matrix polymer and CMS-Na as the pushing layer material to prepare double-layer osmotic pump-type controlled release tablets,and to study the scale-up parameters and to evaluate human bioequivalence.Methods:The single variable method is used to investigate the factors that might affect the dissolution curve of nifedipine controlled-release tablets,such as the type of disintegrants,the amount of CMS-Na and copovidone in the pushing layer,the weight gain of semi-osmotic membrane coating,and the size of laser drilling,etc.The formulation is optimized for process parameters and evaluated with human bioequivalence study.Results:Formulation is selected with CMS-Na as expansion material,povidone and copovidone as matrix material,carbomer as sustained-release material.The sample similarity factor(f_(2) value)prepared by the prescription is greater than 50,and the dissolution curve is similar to that of the reference preparation.The process amplification results show that the process reproducibility of the self-developed controlled-release film is good,and the f_(2) value is greater than 50,which is suitable for large-scale production.In vivo bioequivalence study shows that the geometric mean ratios and 90%confidence intervals of C_(max),AUC_(0-t)and AUC_(0-∞)of the tested formulation to the reference formulation are 107.58%(88.84%,130.27%),99.33%(86.27%,114.35%),and 99.43%(87.89%,112.49%),which fell within the acceptable range.Conclusion:The formulation of test nifedipine controlled-release tablets is successfully developed,the formulation process is feasible,and the tested formulation is bioequivalent with the reference formulation.