Analysis of molecular weight of mixed poly (lactide-co-glycolide) in Risperidone microspheres based on separation method.

Abstract

Poly(lactide-co-glycolide) polymers (PLGAs) are indispensable biodegradable matrices for long-acting parenteral (injectable) microsphere formulations. To modulate drug release kinetics and mitigate burst release in these complex injectable systems, PLGAs with varying lactide:glycolide (L:G) ratios are often employed in combination. While essential for ensuring batch-to-batch consistency and developing generic long-acting injectables, characterizing the individual properties of mixed PLGAs remains technically challenging. This study establishes a simple and accurate method to separate and characterize PLGA 7525 5A and PLGA 5050 2.5A within risperidone microspheres based on their solubility differences (semi-solvent principle). Trichloroethylene was identified as the optimal separation solvent, with n-propyl acetate serving as the washing solvent. The method was optimized by investigating parameters such as solvent volume, temperature, and mechanical assistance, with the addition of glass beads proving critical for effective separation. Molecular weight (Mw) analysis was performed using Gel Permeation Chromatography (GPC) on Agilent PLgel columns (connected in series) with tetrahydrofuran (THF) as the mobile phase. The method demonstrated excellent linearity (R2 = 0.9998) within the calibration range of 1220-554,000 g·mol⁻¹ (Polystyrene equivalent). Precision was high, with RSD values of 0.33% (n=6) for the supernatant Mw and 2.1% (n=6) for the sediment Mw. The method's discriminatory ability was validated using simulated single-polymer degradation and mixed degraded microspheres. In conclusion, this method enables independent quality control of individual PLGA components within complex injectable matrices, providing a vital analytical tool for the key characteristic evaluation and bioequivalence assessment of complex generic parenteral formulations.