Long-acting PLGA microspheres: advances in excipient and product analysis toward improved product understanding

Abstract

Poly(lactic-co-glycolic acid) (PLGA) microspheres are a sustained-release drug delivery system with several successful commercial products used for the treatment of a variety of diseases. By utilizing PLGA polymers with different compositions, therapeutic agents can be released over durations varying from several weeks to several months. However, precise quality control of PLGA polymers and a fundamental understanding of all the factors associated with the performance of PLGA microsphere formulations remains challenging. This knowledge gap can hinder product development of both innovator and generic products.

In this review, variability of the key release controlling excipient (PLGA), as well as advanced physicochemical characterization techniques for the PLGA polymer and PLGA microspheres are discussed. The relative merits and challenges of different in vitro release testing methods, in vivo pharmacokinetic studies, and in vitro-in vivo correlation development are also summarized. This review is intended to provide an in-depth understanding of long-acting microsphere products and consequently facilitate the development of these complex products.

Conclusions

In conclusion, although significant advances have been reported in microsphere development, there is still a lack of in-depth understanding and clear guidance for quality control (excipients and formulations), as well as for product performance. Advanced understanding of both the release controlling excipients and complex formulations can be achieved with current cutting-edge technologies, including: 1) multi angle static light scattering for molecular weight analysis; 2) liquid/solid state.