Mechanistic insight into the effect of tacticity of poly(methyl methacrylate) on crystallization of amorphous griseofulvin: excluding monomer and end-group effects

Polymers have been widely used to physically stabilize amorphous drugs by forming amorphous solid dispersions (ASDs), resulting in commercial and clinical success as a pharmaceutical technique to improve the bioavailability of a poorly water-soluble drug. However, the role of polymers in maintaining the physical stability of ASDs has not been fully understood. Herein, we investigated how poly(methyl methacrylates) (PMMAs) with different tacticities impact the liquid dynamics and crystallization kinetics of amorphous griseofulvin (GSF). PMMAs with similar chain lengths and identical monomer structures were selected, aiming to exclude effects arising from differences in monomer structure and end groups. The syndiotactic form of PMMA (s-PMMA) exhibited a stronger inhibitory effect on the crystal growth of amorphous GSF in comparison with isotactic (i-PMMA) and atactic (a-PMMA) forms. Effects of the isotactic atactic forms of PMMA on the crystal growth of GSF can be mainly attributed to their molecular mobility, as shown by the overlapping of the logarithm growth rate curves versus viscosity and α-relaxation time. However, the crystal growth rate curves of GSF in the system containing 10 wt% s-PMMA did not overlap with those of the pure GSF system. These results suggest that liquid dynamics is not a main contributor to the inhibitory effect of s-PMMA during drug crystallization.