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  5. Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios
  1. The FDA Science Forum

2021 FDA Science Forum

Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios

Authors:
Poster Author(s)
Qin, Bin, FDA/CDER; Garner, John, Akina, Inc.; Hadar, Justin, Akina, Inc.; Skidmore, Sarah, Akina Inc., Jessmon, Faye, Akina Inc.; Park, Haesun, Akina Inc., Park, Kinam, Akina, Inc., Wang, Yan, FDA/CDER, Jhon, Young, FDA/CDER
Center:
Contributing Office
Center for Drug Evaluation and Research

Abstract

Poster Abstract

Background

Poly(lactide-co-glycolide) (PLGA) is a biodegradable and biocompatible polymer widely used in medical applications. Previous studies have identified a series of semi-solvents which exhibit conditional PLGA solubility depending on the lactide:glycolide (L:G) ratio [1]. Certain patterns of solvents which exhibit this property have emerged including the tendency for esters and ketones to exhibit this property.

Purpose

The purpose of this study is to examine the effect of solvent isomeric structures on the PLGA solubility.

Methodology

PLGAs of varying L:G ratios were tested for dissolution in selected solvents and their isomers. The molecular weights of the PLGAs was characterized by gel permeation chromatography and ranged from approximately 60 kDa to 90 kDa. The L:G ratios of the PLGAs tested varied from 50:50 to 100:0 and were confirmed by nuclear magnetic resonance prior to use. A sample of each PLGA (100 mg) was incubated in 4 mL of each solvent with 100 RPM orbital agitation at 30°C overnight. The solvent was decanted and the remaining polymer was dried to a constant mass at 50-60°C under deep vacuum. Molar volumes were determined for each solvent using ACD/ChemSketch 2015 Pack 2 software.

Results

We observed that increasing length of the ketones or esters caused the solubility of PLGA to become more lactide-dependent for the solvents, requiring higher lactide content within the PLGA to dissolve. Analysis of isomers indicated that there was a general trend that relatively lower molar volumes (one indication of molecule size) improved the dissolution of PLGAs at lower glycolide content.

Conclusion

The molecular configuration of a solvent appears to be a factor affecting PLGA dissolution. These results suggest a relationship between the relative ability of a solvent to penetrate in between potentially glycolide-rich crystalline regions in its ability to dissolve PLGA. Solvent-dependent PLGA dissolution is useful in the manufacturing of PLGA-based formulations, as well as separation of PLGA mixtures for the evaluation of polymer composition sameness.

Acknowledgements

This work was supported by the Broad Agency Announcement (BAA) Contract # 75F40119C10096 from the U.S. Food and Drug Administration (FDA). The content is solely the responsibility of the authors and does not necessarily represent the official views or policies of the U.S. FDA.

References

[1] Sarah Skidmore, Justin Hadar, John Garner, Haesun Park, Kinam Park, Yan Wang, and Xiaohui (Jeff) Jiang. "Complex sameness: Separation of mixed poly(lactide-co-glycolide)s based on the lactide: glycolide ratio." Journal of Controlled Release 300 (2019): 174-184.

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