Zhang Chengqian, Zhang Rui, Liu Lin, Yang Mingshi
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Wuya College of Innovation, Shenyang Pharmaceutical University, 110016 Shenyang, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, 110016 Shenyang, China.
Int J Pharm. 2025 Oct 15;683:126083. doi: 10.1016/j.ijpharm.2025.126083. Epub 2025 Aug 14.
Long-acting injectables (LAIs) present significant advantages over conventional oral formulations, including sustained drug release, reduced dosing frequency, improved patient adherence, and enhanced therapeutic outcomes. Poly (lactic-co-glycolic acid) (PLGA) and polylactic acid (PLA) have emerged as the most widely used polymers for LAIs over the past decades due to their excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and mechanical strength. Among the various manufacturing techniques employed to produce PLGA-based LAIs, spray-drying has gained increasing attention as a fast, one-step process capable of continuous microparticle production with inherent scalability and particle engineering flexibility. Critical physicochemical properties of spray-dried (SD) microparticles, such as size, morphology, drug loading/encapsulation efficiency, and drug release kinetics, can be precisely tuned by optimizing spray-drying process parameters and material attributes. This review summarizes key advances in SD PLGA-based LAIs, beginning with an overview of PLGA as a foundational material for long-acting formulations. We then discuss the fundamental principles of spray-drying and particle formation mechanism, along with different modes of spray-drying PLGA-based LAIs. Next, critical considerations for developing PLGA-based LAIs via spray-drying are examined. Finally, we highlight current challenges and limitations in SD PLGA-based LAIs development, providing insights into future opportunities.
长效注射剂相较于传统口服制剂具有显著优势，包括药物持续释放、给药频率降低、患者依从性提高以及治疗效果增强。在过去几十年中，聚乳酸-羟基乙酸共聚物（PLGA）和聚乳酸（PLA）因其出色的生物相容性、生物降解性、无毒性、非免疫原性和机械强度，已成为长效注射剂中使用最广泛的聚合物。在用于生产基于PLGA的长效注射剂的各种制造技术中，喷雾干燥作为一种快速的一步法工艺受到越来越多的关注，该工艺能够连续生产微粒，具有固有的可扩展性和颗粒工程灵活性。通过优化喷雾干燥工艺参数和材料属性，可以精确调节喷雾干燥（SD）微粒的关键物理化学性质，如尺寸、形态、载药量/包封率和药物释放动力学。本综述总结了基于SD PLGA的长效注射剂的关键进展，首先概述PLGA作为长效制剂的基础材料。然后我们讨论喷雾干燥的基本原理和颗粒形成机制，以及基于PLGA的长效注射剂的不同喷雾干燥模式。接下来，研究了通过喷雾干燥开发基于PLGA的长效注射剂的关键考虑因素。最后，我们强调了基于SD PLGA的长效注射剂开发目前面临的挑战和局限性，并对未来的机遇提供见解。
