Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib.

The effectiveness of different polymers, alone or in combination, in inhibiting the crystallization of celecoxib (CEX) fromamorphous solid dispersions (ASDs) exposed to different temperatures and relative humiditieswas evaluated. It was found that polyvinylpyrrolidone (PVP) and PVP-vinyl acetate formed stronger or more extensive hydrogen bonding with CEX than cellulose-based polymers. This, combined with their better effectiveness in raising the glass transition temperature (Tg) of the dispersions, provided better physical stabilization of amorphous CEX against crystallization in the absence of moisture when compared with dispersions formedwith cellulose derivatives. In ternary dispersions containing 2 polymers, the physical stabilitywas minimally impaired by the presence of a cellulose-based polymer when the major polymer present was PVP. On exposure tomoisture, stability of the CEX ASDswas strongly affected by both the dispersion hygroscopicity and the strength of the intermolecular interactions. Binary and ternary ASDs containing PVP appeared to undergo partial amorphouseamorphous phase separation when exposed 94% relative humidity, followed by crystallization, whereas other binary ASDs crystallized directly without amorphouseamorphous phase separation. [ABSTRACT FROM AUTHOR]