Journal
MOLECULAR PHARMACEUTICS
Volume 2, Issue 5, Pages 384-391Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp050004g
Keywords
celecoxib; PVP; amorphous; molecular interaction
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Stabilization of an amorphous solid against devitrification can be achieved using additives that interact specifically with the parent molecule, and restrain it from rearranging into a crystal lattice. The amorphous form of celecoxib (CEL) was stabilized by poly(vinylpyrrolidone) (PVP), both in the solid state and during dissolution. A comprehensive characterization of CEL-PVP binary amorphous systems by thermal, spectroscopic, and computer simulation techniques provided greater insight into the molecular interaction between the two species. PVP antiplasticized the amorphous CEL, thus raising its glass transition temperature (T-g) and restricting the molecular mobility. The T-gmix values for CEL-PVP binary amorphous systems of varying composition showed positive deviation from those predicted through the Gordon-Taylor/ Kelley-Bueche equation, thus indicating a molecular interaction between CEL and PVP. This was further substantiated by shifts observed in DSC melting endotherms of CEL, and FTIR bands for C = O stretching vibrations in PVP for CEL-PVP binary amorphous systems. Computer simulation showed stronger H-bonds between amido protons of CEL and carbonyl 0 of a monomeric unit of PVP, compared to those observed in pure amorphous CEL. These molecular interactions between CEL and PVP supported the stabilizing action of PVP for the amorphous form of CEL.
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