基于质量源于设计的尼莫地平速分散片的开发：制剂特性与释放动力学评价。

Quality-by-design based development of fast dispersible nimodipine tablets: Formulation attributes and release kinetic assessment.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Federal Urdu University of Arts, Science & Technology, Karachi, Pakistan.

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Pak J Pharm Sci. 2023 Mar;36(2):547-556.

PMID:37530164

Abstract

In the present study fast dispersible nimodipine tablets were developed by direct compression method using quality by design (QbD) approach as per the central composite design by selecting avicel PH 102 (X1) and crospovidone (X2) as independent variables while % friability (R1), disintegration (R2) and hardness (R3) as output variables. Powder blends were assessed for flow characterization. At post compressional stage, several quality assessments were carried out. Particles morphology was observed using scanning electron microscopy (SEM). The stability study on the drug and optimized formulation were determined using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). RSM plots expressed the interaction of avicel PH 102 and crospovidone to determine the adequate quantities of excipients for the optimized formulation. Polynomial equations were used to validate the experimental design. The optimized formulations were evaluated for friability, disintegration and hardness. Results indicated that formulation (F4) containing avicel PH 102 (35%) and crospovidone (5%) was selected as best optimized formulation having friability 0.59%, disintegration 9 sec, % dissolution 95.703% and hardness 4.14 kg. Results of kinetics models indicated that all the developed formulations followed weibull model.

摘要

在本研究中，通过直接压缩法制备了速崩硝苯地平片，采用质量源于设计（QbD）方法，根据中心复合设计，选择微晶纤维素 PH102（X1）和交联聚维酮（X2）为自变量，而 %脆碎度（R1）、崩解（R2）和硬度（R3）为输出变量。对粉末混合物进行了流动特性评估。在压缩后阶段，进行了多项质量评估。使用扫描电子显微镜（SEM）观察颗粒形态。采用热重分析（TGA）和差热分析（DTA）对药物和优化配方进行了稳定性研究。RSM 图表示了微晶纤维素 PH102 和交联聚维酮的相互作用，以确定优化配方的适当赋形剂用量。使用多项式方程验证了实验设计。对优化配方进行了脆碎度、崩解和硬度评估。结果表明，含有微晶纤维素 PH102（35%）和交联聚维酮（5%）的配方（F4）被选为最佳优化配方，其脆碎度为 0.59%、崩解时间为 9 秒、%溶解度为 95.703%、硬度为 4.14kg。动力学模型的结果表明，所有开发的配方均遵循 Weibull 模型。