Designing long-acting injectable formulations using PLGA via spray-drying

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.