University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, H-6720 Szeged, Eötvös u. 6, Hungary.
University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, H-6720 Szeged, Eötvös u. 6, Hungary.
Int J Pharm. 2019 May 1;562:11-22. doi: 10.1016/j.ijpharm.2019.03.021. Epub 2019 Mar 13.
In this study, authors adapt the Quality by Design (QbD) concept as well as the Risk Assessment (RA) method to the early development phase of a new nano-sized liposomal formulation for nasal administration with brain target. As a model active agent, a BCS II class drug was chosen to investigate the behaviour of the drugs with lipophilic character. This research presents how to apply this risk-focused approach and concentrates on the first four stages of the QbD implementation. In this way the quality target product profile was defined, the critical factors were identified and an RA was performed. The RA results helped in the factorial design-based liposome preparation by the lipid film hydration method. The prepared liposomes were evaluated (vesicle size, size distribution, and specific surface area). The surface characteristics were also investigated to verify the exactness of the RA and critical factors based theoretical prediction. The results confirm that the QbD approach in liposome development can improve the formulation process. The RA focused predictive approach resulted in a decreased number of studies in practice but in an effective product preparation. Using such innovative design and development models can help to optimise and rationalise the development of liposomes.
在这项研究中，作者将质量源于设计（QbD）概念和风险评估（RA）方法应用于新型经鼻脑靶向纳米脂质体制剂的早期开发阶段。选择一种 BCS II 类药物作为亲脂性药物模型，研究其行为。本研究介绍了如何应用这种以风险为重点的方法，并集中在 QbD 实施的前四个阶段。通过这种方式，定义了质量目标产品概况，确定了关键因素并进行了 RA。RA 结果有助于通过脂质体薄膜水化法进行基于因子设计的脂质体制备。对制备的脂质体进行了评估（囊泡大小、粒径分布和比表面积）。还对表面特性进行了研究，以验证 RA 和基于关键因素的理论预测的准确性。结果证实，QbD 方法在脂质体开发中可以改善制剂工艺。RA 集中的预测方法减少了实际研究的数量，但提高了产品制备的效果。使用这种创新的设计和开发模型有助于优化和合理化脂质体的开发。
