Meeting the unmet: from traditional to cutting-edge techniques for poly lactide and poly lactide-co-glycolide microparticle manufacturing

Abstract

Background Polylactides (PLA) and poly lactide-co-glycolides (PLGA) undoubtedly are among the major drivers in the pharmaceutical market. Their relevance in pharmaceutics and biomedicine is well established in light of their sustainability, safety, tunable biodegradability, and versatility. However, polymer degradability and plasticity can somehow restrain industrial developability of PLA and PLGA formulations, especially in the form of microparticles (MP). Area covered This review wants to deal with the known manufacturing issues of PLA/PLGA MP, debating the potential contribution of modern and cutting-edge manufacturing technologies to the solution of unmet production needs. Technological and regulatory aspects will be considered outlining the potential role of advanced manufacturing techniques in the advancement of PLA/PLGA MP production processes. Expert opinion The multifaceted complexity of PLA/PLGA MP manufacturing processes demands adequate standardization and updated guidelines covering the so far unmet industrialization requirements. Novel and evolving manufacturing technologies will surely support the future development of bench-to-production plant transfer for such products. Careful evaluation of production costs is demanded in order to ensure process sustainability and patient's outreach.

Poly(lactic acid)/poly(lactic-co-glycolic acid)-based microparticles: an overview

“…In 1986, Debiopharm launched on the market Decapeptyl ® SR, a triptorelin sustained release formulation based on injectable PLGA microspheres for the treatment of prostate cancer (Sanders et al 1984;Tice 2017). In 1989 Lupron Depot ® , a microparticle formulation of leuprolide acetate for the treatment of prostate cancer, was approved, followed by Parlodel LA ® (bromocriptine mesilate), Sandostatin LAR ® (octreotide acetate), and many others (Schoubben et al 2019). As mentioned, more than 15 products based on PLA/PLGA microparticles have been approved and marketed.…”

“…By considering also different PLA/PLGA formulations, such as preformed and in situ forming depots, more than 35 products have been successfully developed (Tice 2017). A list of the medicinal products based on PLA/PLGA microparticles can be found in recent reviews (Wischke and Schwendeman 2012;Jain et al 2016;Zhong et al 2018;Schoubben et al 2019).…”

“…All these methodologies were proposed and optimized in the 1990s and early 2000s for the preparation of PLA/PLGA microspheres (DeLuca et al 1993;Conte et al 1994;Li et al 1995;Thomasin et al 1998;Lee et al 2006). Now, most commercialized products are prepared by solvent diffusion/ evaporation, solvent extraction, phase separation, and spray drying methods (Schoubben et al 2019).…”

“…The solvent diffusion/evaporation technique can be considered the classical preparation method for polyester microparticles since it has been largely employed for research purposes at the laboratory scale and also in the manufacturing of some commercial products (O'Donnell and McGinity 1997;Schoubben et al 2019). The solvent diffusion/evaporation technique has been extensively exploited at the laboratory scale and the results published in a wide range of articles have surely contributed to the success of PLGA microspheres as injectable DDSs.…”

Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair

“…As an alternative to peptide-mediated delivery of PNAs, several groups have investigated the use of NPs. While many of these delivery systems have been reviewed elsewhere [80], efforts have focused on developing NPs from poly(lactic-co-glycolic acid) (PLGA), a biocompatible and biodegradable polymer, well-known to the FDA [81]. In addition to their favorable safety profiles [82,83], drug release from PLGA NPs is highly tunable by adjusting polymer molecular weight and ratio of lactic to glycolic acid [84].…”