Formulation composition, manufacturing process, and characterization of poly(lactide-co-glycolide) microparticles

JOURNAL OF CONTROLLED RELEASE

卷:329

Article

Park, Kinam^1,2  Otte, Andrew¹  Sharifi, Farrokh¹  Garner, John²  Skidmore, Sarah²  Park, Haesun²  Jhon, Young Kuk³  Qin, Bin⁴  Wang, Yan⁴ 

[1] Purdue Univ, Biomed Engn & Pharmaceut, 206 S Martin Jischke Dr, W Lafayette, IN 47907 USA

[2] Akina Inc, 3495 Kent Ave,Suite A200, W Lafayette, IN 47906 USA

[3] Food & Drug Adm, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA

[4] Food & Drug Adm, Off Gener Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA

关键词: PLGA;    Manufacturing parameters;    Surface morphology;    Solvent/water exchange;    Interfacial instability;    Capillary pressure;    Drug release kinetics;   

DOI  :  10.1016/j.jconrel.2020.10.044

来源: Elsevier

【 摘 要 】

Injectable long-acting formulations, specifically poly(lactide-co-glycolide) (PLGA) based systems, have been used to deliver drugs systemically for up to 6 months. Despite the benefits of using this type of long-acting formulations, the development of clinical products and the generic versions of existing formulations has been slow. Only about two dozen formulations have been approved by the U.S. Food and Drug Administration during the last 30 years. Furthermore, less than a dozen small molecules have been incorporated and approved for clinical use in PLGA-based formulations. The limited number of clinically used products is mainly due to the incomplete understanding of PLGA polymers and the various variables involved in the composition and manufacturing process. Numerous process parameters affect the formulation properties, and their intricate interactions have been difficult to decipher. Thus, it is necessary to identify all the factors affecting the final formulation properties and determine the main contributors to enable control of each factor independently. The composition of the formulation and the manufacturing processes determine the essential property of each formulation, i.e., in vivo drug release kinetics leading to their respective pharmacokinetic profiles. Since the pharmacokinetic profiles can be correlated with in vitro release kinetics, proper in vitro characterization is critical for both batch-to-batch quality control and scale-up production. In addition to in vitro release kinetics, other in vitro characterization is essential for ensuring that the desired formulation is produced, resulting in an expected pharmacokinetic profile. This article reviews the effects of a selected number of parameters in the formulation composition, manufacturing process, and characterization of microparticle systems. In particular, the emphasis is focused on the characterization of surface morphology of PLGA microparticles, as it is a manifestation of the formulation composition and the manufacturing process. Also, the implication of the surface morphology on the drug release kinetics is examined. The information described here can also be applied to in situ forming implants and solid implants.

【 授权许可】

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