Wu Helen Haixia, Garidel Patrick, Michaela Blech
Boehringer Ingelheim Pharma GmbH & Co. KG, Innovation Unit, Pharmaceutical Development Biologicals, Biberach an der Riss, Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Innovation Unit, Pharmaceutical Development Biologicals, Biberach an der Riss, Germany.
Int J Pharm. 2021 May 15;601:120531. doi: 10.1016/j.ijpharm.2021.120531. Epub 2021 Mar 26.
The main challenge to develop HCF for IgG and Ig-based therapeutics is to achieve essential solubility, viscosity and stability of these molecules in order to maintain product quality and meet regulatory requirement during manufacturing, production, storage, shipment and administration processes. The commonly used and FDA approved excipients for IgG and Ig -based therapeutics may no longer fulfil the challenge of HCF development for these molecules to certain extent, especially for some complex Ig-based platforms. 2-Hydroxypropyl beta-cyclodextrin (HP-β-CD) is one of the promising excipients applied recently for HCF development of IgG and Ig-based therapeutics although it has been used for formulation of small synthesized chemical drugs for more than thirty years. This review describes essential aspects about application of HP-β-CD as excipient in pharmaceutical formulation, including physico-chemical properties of HP-β-CD, supply chain, regulatory, patent landscape, marketed drugs with HP-β-CD, analytics and analytical challenges, stability and control strategies, and safety concerns. It also provides an overview of different studies, and outcomes thereof, regarding formulation development for IgGs and Ig-based molecules in liquid and solid (lyophilized) dosage forms with HP-β-CD. The review specifically highlights the challenges for formulation manufacturing of IgG and Ig-based therapeutics with HP-β-CD and identifies areas for future work in pharmaceutical and formulation development.
开发用于基于IgG和Ig的治疗药物的高浓度配方（HCF）的主要挑战在于实现这些分子的基本溶解性、粘度和稳定性，以便在制造、生产、储存、运输和给药过程中保持产品质量并满足监管要求。对于基于IgG和Ig的治疗药物，常用的且已获美国食品药品监督管理局（FDA）批准的辅料在一定程度上可能不再满足这些分子高浓度配方开发的挑战，特别是对于一些复杂的基于Ig的平台。2-羟丙基-β-环糊精（HP-β-CD）是最近应用于基于IgG和Ig的治疗药物高浓度配方开发的有前景的辅料之一，尽管它已用于小合成化学药物的制剂超过三十年。本综述描述了HP-β-CD作为辅料在药物制剂中的应用的基本方面，包括HP-β-CD的物理化学性质、供应链、监管、专利情况、含HP-β-CD的上市药物、分析及分析挑战、稳定性和控制策略以及安全性问题。它还概述了关于使用HP-β-CD的液体和固体（冻干）剂型中IgG和基于Ig的分子的配方开发的不同研究及其结果。该综述特别强调了使用HP-β-CD进行基于IgG和Ig的治疗药物制剂制造的挑战，并确定了药物和制剂开发未来工作的领域。
