Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
Purdue University, Weldon School of Biomedical Engineering, West Lafayette, IN 47907, USA.
Int J Pharm. 2022 Oct 15;626:122170. doi: 10.1016/j.ijpharm.2022.122170. Epub 2022 Sep 5.
A thorough understanding of the complexities in formulating and manufacturing polymeric microspheres is required for new and generic drug applications. Specifically, for an ANDA application for polymeric microsphere-based products, the applicant must meet Q1 (qualitative) and Q2 (quantitative) sameness, and in some cases, Q3 (e.g., microstructural) sameness. Herein, we report the naltrexone crystallinity in a PLGA microparticle system prepared from a dichloromethane-benzyl alcohol solvent system results in a crystallinity dependence as a function of microparticle size from the same batch - illustrating intrabatch microstructural variability. As the particle size increases, the crystallinity increases, with additional polymorphic forms more readily noted at the large particle sizes. Furthermore, during dissolution, a polymorphic transition and/or crystallization occurs at larger size fractions. This study highlights the importance of controlling the manufacturing parameters during microparticle formation, specifically solvent extraction and particle size control. Furthermore, with the approval of generic microparticles formulations on the horizon, this study highlights the importance of Q3, the same components in the same concentration with the same arrangement of matter, whereby microparticles can have varying microstructural properties across particle sizes from the same batch.
对于新的和仿制药应用，需要深入了解聚合物微球的配方和制造的复杂性。具体来说，对于基于聚合物微球的产品的仿制药申请，申请人必须满足 Q1（定性）和 Q2（定量）相同，在某些情况下，还必须满足 Q3（例如微观结构）相同。本文报道了在由二氯甲烷-苯甲醇溶剂体系制备的 PLGA 微球系统中纳曲酮的结晶度，结果表明结晶度与同一批微球的粒径有关-说明了批内微观结构的可变性。随着粒径的增加，结晶度增加，较大粒径更容易出现额外的多晶型形式。此外，在溶解过程中，较大的粒径会发生多晶型转变和/或结晶。这项研究强调了在微球形成过程中控制制造参数的重要性，特别是溶剂萃取和粒径控制。此外，随着仿制药微球制剂的批准即将到来，这项研究强调了 Q3 的重要性，即相同成分、相同浓度和相同物质排列，从而使得微球可以在同一批中具有不同的微观结构特性。
