Evaluate the ability of PVP to inhibit crystallization of amorphous solid dispersions by density functional theory and experimental verify.

Abstract In this study, we used density functional theory (DFT) to predict polymer-drug interactions, and then evaluated the ability of poly (vinyl pyrrolidone) (PVP) to inhibit crystallization of amorphous solid dispersions by experimental-verification. Solid dispersions of PVP/resveratrol (Res) and PVP/griseofulvin (Gri) were adopted for evaluating the ability of PVP to inhibit crystallization. The density functional theory (DFT) with the B3LYP was used to calculate polymer-drug and drug-drug interactions. Fourier transform infrared spectroscopy (FTIR) was used to confirm hydrogen bonding interactions. Polymer-drug miscibility and drug crystallinity were characterized by the modulated differential scanning calorimetry (MDSC) and X-ray powder diffraction (XRD). The release profiles were studied to investigate the dissolution advantage. DFT results indicated that E PVP-Res  > E Res-Res (E: represents hydrogen bonding energy). A strong interaction was formed between PVP and Res. In addition, Fourier transform infrared spectroscopy (FTIR) analysis showed hydrogen bonding formed between PVP and Res, but not between PVP and Gri. MDSC and XRD results suggested that 70–90 wt% PVP/Res and PVP/Gri solid dispersions formed amorphous solid dispersions (ASDs). Under the accelerated testing condition, PVP/Res dispersions with higher miscibility quantified as 90/10 wt% were more stable than PVP/Gri dispersions. The cumulative dissolution rate of 90 wt% PVP/Res dispersions still kept high after 90 days storage due to the strong interaction. However, the cumulative dissolution rate of PVP/Gri solid dispersions significantly dropped because of the recrystallization of Gri.