College of Pharmacy, California Health Science University, Clovis, CA 93612, USA.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.
Adv Drug Deliv Rev. 2019 Nov-Dec;151-152:56-71. doi: 10.1016/j.addr.2019.03.003. Epub 2019 Mar 18.
Given the successful entry of several liposomal drug products into market, and some with decades of clinical efficacy, liposomal drug delivery systems have proven capabilities to overcome certain limitations of traditional drug delivery, especially for toxic and biologic drugs. This experience has helped promote new liposomal approaches to emerging drug classes and current therapeutic challenges. All approved liposomal dosage forms are parenteral formulations, a pathway demonstrating greatest safety and efficacy to date. Due to the intrinsic instability of aqueous liposomal dispersions, lyophilization is commonly applied as an important solution to improve liposomal drug stability, and facilitate transportation, storage and improve product shelf-life. While lyophilization is a mature pharmaceutical technology, liposome-specific lyophilization platforms must be developed using particular lyophilization experience and strategies. This review provides an overview of liposome formulation-specific lyophilization approaches for parenteral use, excipients used exclusively in liposomal parenteral products, lyophilized liposome formulation design and process development, long-term storage, and current regulatory guidance for liposome drug products. Readers should capture a comprehensive understanding of formulation and process variables and strategies for developing parenterally administered liposomal drugs.
鉴于几种脂质体药物产品已成功进入市场，并且其中一些已有数十年的临床疗效，脂质体药物递送系统已被证明具有克服传统药物递送某些局限性的能力，特别是对于毒性药物和生物药物。这一经验有助于推动针对新兴药物类别和当前治疗挑战的新脂质体方法。所有批准的脂质体剂型均为注射剂，这是迄今为止证明具有最大安全性和疗效的途径。由于水性脂质体分散体的固有不稳定性，冷冻干燥通常被用作提高脂质体药物稳定性、便于运输、储存和延长产品保质期的重要解决方案。虽然冷冻干燥是一种成熟的制药技术，但必须使用特定的冷冻干燥经验和策略来开发专门针对脂质体的冷冻干燥平台。本综述概述了用于注射用途的脂质体制剂特定冷冻干燥方法、专门用于脂质体注射产品的赋形剂、冷冻干燥脂质体制剂的设计和工艺开发、长期储存以及当前脂质体药物产品的监管指南。读者应全面了解用于开发注射用脂质体药物的制剂和工艺变量及策略。
