Enhancement of Dissolution Rate of Valdecoxib Using Solid Dispersions with Polyethylene Glycol 4000

Abstract

The aim of the present study was to enhance the dissolution rate of valdecoxib using its solid dispersions (SDs) with polyethylene glycol (PEG) 4000. The phase solubility behavior of valdecoxib in the presence of various concentrations of PEG 4000 in water was obtained at 37°C. The solubility of valdecoxib increased with increasing amount of PEG 4000 in water. Gibbs free energy (ΔG°_tr) values were all negative, indicating the spontaneous nature of valdecoxib solubilization, and they decreased with increase in the PEG 4000 concentration, demonstrating that the reaction conditions became more favorable as the concentration of PEG 4000 increased. The SDs of valdecoxib with PEG 4000 were prepared at 1:1, 1:2, 1:5, and 1:10 (valdecoxib: PEG 4000) ratio by melting method. Evaluation of the properties of the SDs was performed by using dissolution, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) studies. The SDs of valdecoxib with PEG 4000 exhibited enhanced dissolution rate of valdecoxib, and the rate increased with increasing concentration of PEG 4000 in SDs. Mean dissolution time (MDT) of valdecoxib decreased significantly after preparation of SDs and physical mixture with PEG 4000. The FTIR spectroscopic studies showed the stability of valdecoxib and absence of well-defined valdecoxib-PEG 4000 interaction. The DSC and XRD studies indicated the amorphous state of valdecoxib in SDs of valdecoxib with PEG 4000. The SEM pictures showed the formation of effective SDs of valdecoxib with PEG 4000, since well-defined changes in the surface nature of valdecoxib, SDs, and physical mixture were observed.

Key Words:

• Valdecoxib
• Solid dispersion
• PEG 4000
• Dissolution
• Solubility