Molecular and thermodynamic aspects of solubility advantage from solid dispersions.
The solubility behavior of solid dispersions of two drugs with similar structures was studied. Valdecoxib (VLB) and etoricoxib (ETB) were used as model drugs, and their solid dispersions were prepared with 1, 2, 5, 10, 15, and 20% w/w poly(vinylpyrrolidone) (PVP) by the quench cooling method. The interactions between the drug and polymer molecules were studied by Fourier transform infrared spectroscopy (FT-IR). The thermodynamic aspects of solubility behavior were studied by plotting van't Hoff plots. Both the drugs showed significant differences in their solubility behavior. In the case of VLB, solubility was found to increase significantly with increasing PVP concentration. ETB however did not show any significant solubility enhancement and was found to have decreased solubility at high PVP concentrations. H-bonding interactions were established between VLB and PVP molecules, while none were observed in ETB-PVP dispersions. Solution thermodynamics of amorphous and crystalline forms of both the drugs were studied by van't Hoff plots. The results obtained showed very high negative value of Gibbs free energy for VLB as compared to ETB, thus demonstrating high spontaneity of VLB solubilization. Entropy of amorphous VLB was found to be highly favorable, while being slightly unfavorable for ETB. From this study H-bonding interactions were found to play a major role in dictating the solubility behavior of these drugs from solid dispersions.
Bansal
Shyam Sunder
SS
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160 062, India. akbansal@niper.ac.in
Kaushal
Aditya Mohan
AM
Bansal
Arvind Kumar
AK
D000077613:Etoricoxib; D007555:Isoxazoles / Q000737:chemistry*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry*; D013816:Thermodynamics; D000096926:Benzenesulfonamides
D000077613:Etoricoxib; D007555:Isoxazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C406224:valdecoxib; D000096926:Benzenesulfonamides