Enhancement of dissolution rate of rofecoxib using solid dispersions with urea

Chengsheng Liu, Kashappa Goud H. Desai, Chenguang Liu, Hyun J. Park

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The aim of this study was to enhance the dissolution rate of rofecoxib using solid dispersions (SDs) with urea. In preliminary studies, the solubility behavior of rofecoxib in the presence of polyethylene glycol (PEG)-4000, polyvinylpyrrolidone (PVP) K30, mannitol, and urea in water was obtained at 37°C to choose an effective carrier for preparing its SDs. A systematic increase in the solubility behavior of rofecoxib was observed with increasing concentrations of these carriers in water except mannitol. The Gibbs free energy (ΔGtro) values were negative indicating the spontaneous nature of rofecoxib solubilization, and it decreased with increases in concentration, demonstrating that the reaction became more favorable as the concentration of these carriers increased. Since, urea exhibited higher solubilizing power than the other carriers, SDs of rofecoxib with urea were prepared at 1:1, 1:2, 1:5, and 1:10 (rofecoxib:urea) ratios by the fusion method. Evaluation of the properties of the SDs was performed using dissolution studies, fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-Ray diffraction (XRD), and scanning electron microscopy (SEM). The dissolution rate of rofecoxib was enhanced rapid by its SDs with urea and increased with increasing concentrations of urea in SDs. The mean dissolution time (MDT) of rofecoxib decreased after preparation of SDs and physical mixtures with urea. FTIR spectroscopic studies showed the stability of rofecoxib and the absence of a well-defined rofecoxib-urea interaction. DSC and XRD studies confirmed the amorphous state of rofecoxib in SDs of rofecoxib with urea. SEM pictures showed the formation of effective SDs of rofecoxib with urea since well-defined changes in the surface nature of rofecoxib, SDs, and physical mixture were observed.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalDrug Development Research
Volume63
Issue number4
DOIs
Publication statusPublished - 2004 Dec

Keywords

  • Dissolution rate
  • MDT
  • Rofecoxib
  • Solid dispersion
  • Solubility
  • Urea

ASJC Scopus subject areas

  • Drug Discovery

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