UCIBIO/REQUIMTE, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
CNC - Center for Neuroscience and Cell Biology, Faculty of Medicine (Pólo I), University of Coimbra, Coimbra, Portugal; FFUC - Faculty of Pharmacy, Pólo das Ciências da Saúde, Coimbra, University of Coimbra, Coimbra, Portugal.
Nanomedicine. 2020 Aug;28:102206. doi: 10.1016/j.nano.2020.102206. Epub 2020 Apr 22.
Quality-by-design (QbD) approach has been applied to optimize lipid-based nanosystems formulations, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions, besides being increasingly requested by regulatory authorities. Different mathematical models and statistical tests have been used, with similar conclusions regarding the parameters that influence the physical features of the resulting nanosystems. These include, variations in composition (e.g. lipid(s) and/or emulsifier(s)) and manufacturing parameters (e.g. emulsification rate and/or time, sonication amplitude and/or time, and homogenization pressure and/or cycles). These are critical parameters that influence nanoparticle/globule mean size, polydispersity index, zeta potential, drug encapsulation efficiency and in vitro drug release. This review addresses the concepts and applications of QbD for the development of lipid-based nanosystems, reporting successful examples published in the last 2 years. Although, some limitations have been identified, it is expected that in the upcoming years the application of QbD in pharmaceutical development will be an established approach.
质量源于设计（QbD）方法已被应用于优化基于脂质的纳米系统制剂，包括固体脂质纳米粒（SLN）、纳米结构脂质载体（NLC）和纳米乳剂，这也是监管机构的日益要求。已经使用了不同的数学模型和统计测试，关于影响所得纳米系统物理特性的参数得出了类似的结论。这些参数包括组成（例如脂质和/或乳化剂）和制造参数（例如乳化速率和/或时间、超声幅度和/或时间以及均质压力和/或循环）的变化。这些是影响纳米粒子/液滴平均粒径、多分散指数、Zeta 电位、药物包封效率和体外药物释放的关键参数。本文综述了 QbD 用于开发基于脂质的纳米系统的概念和应用，报告了过去 2 年中发表的成功实例。尽管已经确定了一些局限性，但预计在未来几年，QbD 在药物开发中的应用将成为一种既定方法。
