PLGA Copolymerization Kinetic Parameter Estimation with Stochastic Modeling

Dai, Jingyi
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Kinetic parameters for the reversible copolymerization of poly(lactide-co-glycolide) (PLGA) provide insight into the resulting sequence, which can affect the performance of PLGA in some pharmaceutical applications such as long-acting implants. The effects of synthesis conditions on kinetic parameters and resulting sequences for PLGA have not yet been fully studied. Because existing reactivity ratio models such as Meyer-Lowry or Beckingham-Sanoja-Lynd are insufficient for copolymerization reactions which include reversibility and transesterification, and complete deterministic descriptions of reversible copolymerization are impractical, a stochastic model was used to determine kinetic parameters from experimental data collected using Fourier-transform infrared (FTIR) spectroscopy. The effect of temperature and reaction volume on rate constants and reactivity ratios were investigated. Preliminary results reveal that individual rate constants increase with increasing temperature. No clear trend was observed for reaction volume. Neither temperature nor reaction volume clearly impacted reactivity ratios. Average reactivity ratios across all experiments were r_G=3.93, r_L=0.23. More iterations of fitting need to be carried out, and experiments need to be repeated for better accuracy. These results are significant because it allows a better understanding of the various reactions during PLGA copolymerization, and the method itself can be modified to determine kinetic parameters for other complex copolymers.