A poly(lactic-co-glycolic acid) (PLGA)-based in situ-forming implant (ISFI) is a long-acting injectable composed of active ingredients, a biodegradable polymer and a biocompatible solvent. Understanding the role of PLGA end-caps is crucial for designing ISFI formulations due to their impact on drug delivery performance. In this study, using leuprolide acetate as a model drug, we characterized the ISFIs using computed tomography (CT) imaging to explore the influence of PLGA end-cap on the implant’s formation and drug-release behavior. CT imaging enabled a detailed characterization of implant morphology and internal structure, providing new insights into the relationship between phase inversion, implant formation, and in vitro release performance. Acid-ended PLGA showed a higher initial burst release with 100% of the solvent released at 9 days and a faster release duration of the drug in the in vitro release profile. In contrast, ester-ended PLGA showed a more prolonged release profile, with the plateau phase not reached until approximately day 50. Morphological analysis from CT images of the in vitro implants revealed that acid-ended PLGA formed spherical implants with a dense outer layer, whereas ester-ended PLGA resulted in irregular shapes with a larger size expansion. In vivo CT imaging confirmed these trends, although implant evolution occurred more rapidly in biological environments. Overall, this research highlights the impact of PLGA end-caps on the performance of ISFI, providing a scientific basis for formulation development, evaluation, and optimization of ISFIs.
Lin et al. (Tue,) studied this question.