Ahmed Osama Abdelhakim Aly, Kurakula Mallesh, Banjar Zainy Mohamed, Afouna Mohsen Ibrahim, Zidan Ahmed Samir
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
Polymer Research Laboratory, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
J Pharm Sci. 2015 Jun;104(6):2062-2075. doi: 10.1002/jps.24448. Epub 2015 Apr 13.
This study is aimed at developing glimepiride (GMD) liposomal films using quality by design (QbD) and process analytical technology (PAT) principles. Risk analysis and Plackett-Burman design were utilized to evaluate formulation variables in two paths. Internal path included liposomal parameters (phosphatidylserine, cholesterol and drug concentrations, and pH of hydration medium). External path constituted films parameters, namely, polymer, plasticizer, and permeation enhancer percentages. As a PAT tool, near infrared (NIR)-based chemometric analysis was used in quantifying GMD contents. Liposomal formulations showed maximum GMD entrapment capacity of 41.9% with vesicular size of 0.51 μm at phospholipid to cholesterol to drug weight ratio of 2:1:0.8. Its transdermal films showed elongation ratio of 75%, folding endurance of 700-fold, 16.6% and 26.8% drug release after 1 and 12 h, respectively. Moreover, 3D response spaces for GMD entrapment and release characteristics were established. Regarding NIR analysis, partial-least-square regression model was accurate in quantifying drug content as indicated by the low root-mean-squared error of calibrations and prediction of 0.031 and 0.032, and bias values of 0.0015 and 0.0021, respectively. In conclusion, this study highlights the level of understanding that can be accomplished through a well-designed research based on QbD and PAT paradigms.
本研究旨在运用质量源于设计（QbD）和过程分析技术（PAT）原则开发格列美脲（GMD）脂质体膜。采用风险分析和Plackett-Burman设计从两条路径评估处方变量。内部路径包括脂质体参数（磷脂酰丝氨酸、胆固醇和药物浓度以及水化介质的pH值）。外部路径构成膜参数，即聚合物、增塑剂和渗透促进剂的百分比。作为一种PAT工具，基于近红外（NIR）的化学计量分析用于定量GMD含量。脂质体制剂在磷脂与胆固醇与药物重量比为2:1:0.8时，显示出最大GMD包封率为41.9%，囊泡大小为0.51μm。其透皮膜的伸长率为75%，耐折性为700次，1小时和12小时后药物释放率分别为16.6%和26.8%。此外，还建立了GMD包封和释放特性的三维响应空间。关于近红外分析，偏最小二乘回归模型在定量药物含量方面是准确的，校准和预测的均方根误差分别为0.031和0.032，偏差值分别为0.0015和0.0021。总之，本研究突出了通过基于QbD和PAT范式精心设计的研究所能达到的理解水平。
