Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia; Global Drug Development Technical Research & Development, Novartis, Biologics Technical Development Mengeš, Drug Product Development, Lek Pharmaceuticals d.d., Kolodvorska 27, SI-1234 Mengeš, Slovenia.
Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Int J Pharm. 2020 May 15;581:119285. doi: 10.1016/j.ijpharm.2020.119285. Epub 2020 Mar 30.
Formulation development is an essential part of any biopharmaceuticals development programme, and this will affect quality, safety and efficacy of the final drug product. The vast majority of biopharmaceuticals on the market are therapeutic proteins; however, these are less stable compared to conventional pharmaceuticals. To counter aggregation, denaturation and surface adsorption of proteins in solution, surfactants are added to the formulations; however, the choice of the best formulation is a challenge that is faced during formulation development. Polysorbates are the most widely used surfactants in the pharmaceutical industry and are presented in >80% of commercial monoclonal antibody formulations. In this review, we provide a general overview of polysorbates and their issues, and the characteristics that have to be taken into account during formulation development. Degradation of polysorbates, namely by hydrolysis and/or oxidation, is one of the main concerns associated with their use. Furthermore, degradation of polysorbates is determined by formulation composition, pH and storage conditions, therefore underlining the importance and complexity of protein formulation development using polysorbates. A need-based approach should be used for correct selection of excipients in protein formulations that contain polysorbates.
制剂开发是任何生物制药开发项目的重要组成部分，这将影响最终药物产品的质量、安全性和疗效。市场上绝大多数的生物制药都是治疗性蛋白，但与传统药物相比，这些蛋白的稳定性较差。为了防止蛋白质在溶液中聚集、变性和表面吸附，表面活性剂被添加到制剂中；然而，选择最佳制剂是制剂开发过程中面临的挑战。聚山梨酯是制药行业中使用最广泛的表面活性剂，存在于 80%以上的商业单克隆抗体制剂中。在这篇综述中，我们提供了聚山梨酯及其问题的概述，以及在制剂开发过程中必须考虑的特性。聚山梨酯的降解，即水解和/或氧化，是与它们的使用相关的主要问题之一。此外，聚山梨酯的降解取决于制剂成分、pH 值和储存条件，因此强调了使用聚山梨酯进行蛋白质制剂开发的重要性和复杂性。对于含有聚山梨酯的蛋白质制剂，应该采用基于需求的方法来正确选择赋形剂。
