Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA; Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, USA.
Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, USA.
J Pharm Sci. 2022 Nov;111(11):2968-2982. doi: 10.1016/j.xphs.2022.08.036. Epub 2022 Sep 2.
Multiple advanced formulations and drug delivery systems (DDSs) have been developed to deliver protein-based biotherapeutics via the subcutaneous (SC) route. These formulations/DDSs include high-concentration solution, co-formulation of two or more proteins, large volume injection, protein cluster/complex, suspension, nanoparticle, microparticle, and hydrogel. These advanced systems provide clinical benefits related to efficacy and safety, but meanwhile, have more complicated formulations and manufacturing processes compared to conventional solution formulations. To develop a fit-for-purpose formulation/DDS for SC delivery, scientists need to consider multiple factors, such as the primary indication, targeted site, immunogenicity, compatibility, biopharmaceutics, patient compliance, etc. Next, they need to develop appropriate formulation (s) and manufacturing processes using the QbD principle and have a control strategy. This paper aims to provide a comprehensive review of advanced formulations/DDSs recently developed for SC delivery of proteins, as well as some knowledge gaps and potential strategies to narrow them through future research.
多种先进的制剂和药物传递系统（DDS）已经被开发出来，以通过皮下（SC）途径输送蛋白类生物治疗药物。这些制剂/DDS 包括高浓度溶液、两种或更多种蛋白质的联合制剂、大容量注射、蛋白质簇/复合物、混悬剂、纳米颗粒、微颗粒和水凝胶。这些先进的系统提供了与疗效和安全性相关的临床益处，但同时与传统的溶液制剂相比，具有更复杂的制剂和制造工艺。为了开发适合 SC 递送的制剂/DDS，科学家需要考虑多个因素，如主要适应证、靶部位、免疫原性、相容性、生物药剂学、患者顺应性等。接下来，他们需要使用 QbD 原则开发合适的制剂并采用制造工艺，并制定控制策略。本文旨在对最近开发的用于蛋白质 SC 递送的先进制剂/DDS 进行全面综述，并讨论一些知识空白和通过未来研究缩小这些空白的潜在策略。
