Solvent-Mediated Polymorphic Transformations in Molten Polymers: The Account of Acetaminophen

Area of Science:

• Materials Science
• Chemical Engineering
• Pharmaceutical Sciences

Background:

• Solvent-mediated polymorphic transformations (SMPTs) are crucial in pharmaceutical formulations.
• Nonconventional solvents like polymer melts are underexplored for SMPTs, limiting polymer-based formulation processes.
• Acetaminophen (ACM) undergoes rapid SMPTs in conventional solvents.

Purpose of the Study:

• To investigate SMPTs of acetaminophen (ACM) in polyethylene glycol (PEG) polymer melts.
• To determine the effect of PEG molecular weight on ACM polymorphic transformation kinetics.
• To establish the relationship between solute diffusivity and SMPT induction time in polymer melts.

Main Methods:

• Utilized in situ Raman spectroscopy to monitor ACM polymorphic transformations.
• Employed polyethylene glycol (PEG) melts with varying molecular weights (4000–35,000 g/mol) as nonconventional solvents.
• Analyzed the induction time for the transformation of ACM II to ACM I.

Main Results:

• The induction time for ACM II to I transformation in PEG melts is significantly longer than in conventional solvents like ethanol.
• Solute diffusivity (D) in PEG melts is substantially lower (5.32 × 10^-11–8.36 × 10^-14 m²/s) compared to ethanol (4.84 × 10^-9 m²/s).
• Induction time correlates with the physicochemical properties (viscosity, η) of the polymer melt, influencing solute diffusion.

Conclusions:

• The rate of SMPTs in polymer melts is governed by solute diffusion kinetics.
• Tuning polymer melt properties allows control over SMPT induction times.
• This understanding enables kinetic access and stabilization of desired polymorphic forms during processing.