Long-acting injectable (LAI) drug delivery systems are a cornerstone of chronic disease management, offering sustained therapeutic concentrations and improved patient adherence. These formulations establish intramuscular or subcutaneous depots to provide controlled drug release, thereby minimizing dosing frequency and pharmacokinetic variability. This comprehensive review articulates the evolution of LAI platforms, from legacy oil-based solutions to advanced biodegradable polymeric microspheres (PLGA), in situ forming gels, lipid-based carriers, and nanosuspensions. The formulation principles, technical advantages, and manufacturing challenges for each technology are critically analyzed. Core drug release mechanisms, including polymer erosion, matrix diffusion, and particle dissolution, are detailed. Furthermore, advanced strategies to manipulate in vivo clearance and extend therapeutic half-life, such as PEGylation, lipidation, and Fc/HSA fusion, are synthesized. A significant focus is placed on product characterization, emphasizing the challenges in developing predictive in vitro release (IVR) methods. Key quality attributes (CQAs) and regulatory pathways are also examined. Finally, emerging technologies, including stimuli-responsive systems and AI-assisted design, are explored to outline future perspectives for enhancing the therapeutic precision and clinical utility of LAIs.
THEYANESHWARAN et al. (Mon,) studied this question.