Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, USA.
Int J Pharm. 2011 Oct 31;419(1-2):52-9. doi: 10.1016/j.ijpharm.2011.07.012. Epub 2011 Jul 19.
The purpose of this study was to extend QbD principles to liposomal drug products containing a hydrophilic active pharmaceutical ingredient (API) to demonstrate both the feasibility and the advantages of applying QbD concepts to liposome based complex parenteral controlled release systems. The anti-viral drug Tenofovir was selected as a model compound. Desired properties for two of the key liposome drug product qualities, namely the particle size and drug encapsulation efficiency, were defined and evaluated. It was observed that the liposome preparation process significantly affects liposome particle size, and this resulted in considerable variation in the drug encapsulation efficiency. Lipid chain length did not have a significant effect on drug encapsulation efficiency. However, lipid concentration did affect the drug encapsulation efficiency with higher lipid concentrations resulting in higher drug encapsulation. The use of risk assessment in this study assisted the identification of eight high risk factors that may impact liposome drug encapsulation efficiency and particle size.
本研究旨在将 QbD 原则扩展到含有亲水性活性药物成分 (API) 的脂质体药物产品，以证明将 QbD 概念应用于基于脂质体的复杂注射控释系统的可行性和优势。抗病毒药物替诺福韦被选为模型化合物。确定并评估了两个关键脂质体药物产品质量的所需特性，即粒径和药物包封效率。结果表明，脂质体制备工艺显著影响脂质体粒径，从而导致药物包封效率有较大差异。脂质链长对药物包封效率没有显著影响。然而，脂质浓度确实会影响药物包封效率，较高的脂质浓度会导致更高的药物包封效率。在本研究中使用风险评估有助于确定可能影响脂质体药物包封效率和粒径的八个高风险因素。
