Stability and Solubility of Celecoxib-PVP Amorphous Dispersions: A Molecular Perspective

Abstract

Purpose. The purpose of the current study is to evaluate the solubility advantage offered by celecoxib (CEL) amorphous systems and to characterize and correlate the physical and thermodynamic properties of CEL and its amorphous molecular dispersions containing poly(vinylpyrrolidone) (PVP).

Methods. The measurement of crystalline content, glass transition temperatures, and enthalpy relaxation was performed using differential scanning calorimetry. Solubility and dissolutions studies were conducted at 37°C to elucidate release mechanisms. Further, the amorphous systems were characterized by polarized light microscopy and X-ray powder diffraction studies.

Results. The PVP content has a prominent effect on the stability and solubility profiles of amorphous systems. A dispersion of 20% w/w PVP with CEL resulted in a maxima in terms of solubility enhancement and lowering of relaxation enthalpy. The release of drug from amorphous molecular dispersions was found to be drug-dependent and independent of the carrier.

Conclusions. The solubility enhancement and enthalpy relaxation studies with respect to PVP concentration helped in a better prediction of role of carrier and optimization of concentration in the use of solid dispersions or amorphous systems. The drug release mechanism is drug-controlled rather than carrier-controlled.