(M1530-11-76) Understanding the Role of Water on the Molecular Mobility of Polymer Systems with Terahertz Spectroscopy

Purpose: Amorphous formulations can be more desirable than crystalline drugs as they have higher bioavailability but are also unstable. Therefore, polymers are usually mixed with drugs as excipients to increase the physical stability of the formulation. One polymer widely used to formulate poorly soluble drugs in the pharmaceutical industry is Kollidon VA 64 (PVP/VA). PVP/VA is hygroscopic, which causes the water content in the formulations to increase over time if not stored under proper conditions. With more water in the formulation, the glass transition temperature (T_g) decreases. Lower T_g is used to indicate a higher tendency for the amorphous formulation to recrystallise and thus have lower physical stability.

Methods: Terahertz time-domain spectroscopy (THz-TDS) is a vibrational spectroscopic technique that probes the system's molecular mobility. It can reliably detect subtle changes in vibrational dipole moments and has a unique sensitivity to the presence of water. In this study, THz-TDS was used to investigate the role of water on the molecular mobility of polymer systems. PVP/VA was melted and quench-cooled to obtain a clear pellet using the MeltPrep vacuum compression moulding tool. The pellet was then stored under different humidity levels (RH of 54%, 65%, 75%) for 24 hours or kept under vacuum ( < 2 mbar) in the terahertz measurement chamber overnight before measurement. All samples were measured using the TeraPulse 4000 spectrometer over the temperature range between 80 to 420 K.

Results: The molecular mobility of dry PVP/VA was found to increase with temperature gradually. As the storage humidity level increases, the molecular mobility increases, as seen from the higher slope observed. The molecular mobility at 80 K is a good indication of relative moisture content between different samples. This suggests that a relative humidity (RH) of 65% is the saturation limit for water absorption onto the polymer. For samples stored at RH = 54%, water starts to evaporate at 300 K. In contrast, for RH = 65-75%, water starts to evaporate at 280 K. This suggests that the water molecules in samples stored at RH = 54% are more tightly bound as more energy (higher temperature) is required for water to evaporate whereas the water molecules in samples stored at RH = 65-75% are more loosely bound given that water evaporates at a lower temperature. At temperatures above 400 K, the molecular mobility in all samples converged, suggesting that all water molecules have evaporated, and the mobility of polymer alone causes the absorption.

Conclusion: THz-TDS can be used to investigate the changes in the interaction between water and polymer systems, here PVP/VA. The relative moisture content, differences between tightly bound and loosely bound water molecules, and changes in molecular mobility can be observed from the terahertz data. Higher humidity levels have higher moisture content absorbed onto the polymer and thus higher mobility. As the humidity level increases, the number of loosely bound water molecules increases, and the loosely bound water molecules evaporate first, followed by the evaporation of tightly bound water molecules.

References: del Pilar Buera, M., Welti-Chanes, J., Lillford, P. J., & Corti, H. R. (Eds.). (2006). Water properties of food, pharmaceutical, and biological materials. CRC Press.
Patel, N. G., & Serajuddin, A. T. (2022). Moisture sorption by polymeric excipients commonly used in amorphous solid dispersion and its effect on glass transition temperature: I. Polyvinylpyrrolidone and related copolymers. International Journal of Pharmaceutics, 616, 121532.

Mobility of PVP/VA stored under different humidity levels for 24 hours at 1 THz.