Influence of the Addition of Trace Amounts of Vinylpyrrolidone-Vinyl Acetate Copolymer (PVPVA) on the Crystallization of Celecoxib Glass.

Although polymers can prevent the crystallization of glassy drugs in amorphous solid dispersions, their stabilization mechanism requires further clarification for an efficient formulation design. This study examined the impact of adding trace amounts (2 or 5 w/w %) of vinylpyrrolidone-vinyl acetate copolymer (PVPVA) on the physical stability of celecoxib (CEL) glass using differential scanning calorimetry and broadband dielectric spectroscopy. Long-term isothermal crystallization studies from 35 to 60 °C revealed that CEL glass was significantly stabilized by the addition of trace amounts of PVPVA. Its stabilization was attributed to the effect of PVPVA on the nucleation process rather than on crystal growth. The addition of PVPVA slowed down the α-relaxation of CEL, whereas it accelerated Johari-Goldstein relaxation. Moreover, the addition of PVPVA effectively slowed down γ- and δ-relaxations. Of these, suppression of γ-relaxation mobility had the most important effect, as it is related to the formation of hydrogen bonding between CEL and PVPVA molecules to inhibit nucleation. Moreover, the change in molecular cooperativity of the CEL glass upon adding PVPVA contributed to the inhibition of nuclei formation due to the decreased nucleation temperature. This study provides detailed insights into the physical stabilization mechanisms of glass using polymeric excipients.