Poly(lactide-co-glycolide) polymers (PLGAs) have been used in many clinical formulations of injectable, long-acting formulations. Frequently, PLGAs having different lactide:glycolide (L:G) ratios, molecular weights (MWs), end-groups, and molecular structures have been used individually or in mixtures. To understand the properties of existing formulations made of PLGAs and to develop new formulations, understanding PLGA properties is essential. Yet, the separation of individual PLGA components from a mixture and their characterization has been challenging due to an incomplete understanding of PLGAs. This study focuses on separating PLGAs based on their molecular properties, such as L:G ratio, molecular weight, and comonomer sequence. The separation of PLGAs exploits the use of semi-solvents that dissolve only PLGAs having lactide contents (L%) above a certain threshold. More semi-solvents have been identified that show a specific transition L% between 50 and 100%. The mechanism study of semi-solvents indicates that semi-solvents, in general, prefer PLGAs with relatively higher L%, lower molecular weight, and higher G-L sequences as opposed to G-G sequences. The examination of a series of esters and ketones indicates that a solvent with lower molar volume is more effective as a semi-solvent. At a similar molar volume, esters are more effective than ketones in dissolving PLGAs with the same L:G ratio. The ability to separate and identify PLGA fractions allows better characterization of existing formulations and higher flexibility in designing new injectable, long-acting PLGA formulations.
Keywords: Comonomer sequence; Esters; Ketones; L:G ratio; Long-acting depot; PLGA; Semi-solvent.
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