Ternary amorphous composites of celecoxib, poly(vinyl pyrrolidone) and meglumine with enhanced solubility.
The present study highlights the development of ternary amorphous composites to enhance the solubility of a poorly soluble crystalline drug, celecoxib (CEL). These systems comprised of an 'amorphous drug,' and its 'stabilizer' and 'solubilizer.' The ternary amorphous system of CEL, poly(vinyl pyrrolidone) (PVP) and meglumine (MEG) (7:2:1 w/w) enhanced CEL solubility by approximately equal to 10.2-fold over that for the crystalline drug, and maintained the thermodynamic stability of the amorphous drug. However, MEG alone was unable to stabilize the amorphous CEL against thermally-induced crystallization, and so gave no solubility advantage. The PVP-MEG combination provided a 'synergistic' enhancement of CEL solubility, as compared to their use alone in the amorphous systems. Phase-solubility studies provided greater insight into molecular mechanisms underlying stability and solubility of these amorphous systems. MEG exhibited phase-specific interaction with CEL molecules, when stabilized by PVP in the amorphous state. The higher solubility of CEL from ternary amorphous systems was also thermodynamically favored, as analyzed by van't Hoff plots. A possible molecular level interaction of MEG with PVP-stabilized amorphous CEL seems to be responsible for the solubility advantage of the CEL-PVP-MEG ternary amorphous system.
Gupta
P
P
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Bansal
A K
AK
D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000032:analysis*; D006207:Half-Life; D008536:Meglumine / Q000032:analysis*; D008859:Microscopy, Polarization; D017711:Nonlinear Dynamics; D010592:Pharmaceutic Aids; D011205:Povidone / Q000032:analysis*; D011720:Pyrazoles / Q000032:analysis*; D012995:Solubility; D013449:Sulfonamides / Q000032:analysis*; D013696:Temperature; D013816:Thermodynamics; D014867:Water
D052246:Cyclooxygenase 2 Inhibitors; D010592:Pharmaceutic Aids; D011720:Pyrazoles; D013449:Sulfonamides; D014867:Water; D008536:Meglumine; D011205:Povidone; D000068579:Celecoxib