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Molecular and Thermodynamic Aspects of Solubility Advantage from Solid Dispersions

Shyam Sunder Bansal^†, Aditya Mohan Kaushal^‡ and Arvind Kumar Bansal*^‡

Department of Pharmaceutics and Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160 062, India

Mol. Pharmaceutics, 2007, 4 (5), pp 794–802

DOI: 10.1021/mp7000796

Publication Date (Web): September 15, 2007

†

Department of Pharmaceutics.

‡

Department of Pharmaceutical Technology (Formulations).

* To whom correspondence should be addressed. Mailing address: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab 160 062, India. Phone: +91-172-2214682-87 . Fax: +91-172-2214692. E-mail: akbansal@niper.ac.in, bansalarvind@yahoo.com.

Abstract

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 vant 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 vant 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 disperions.