Solubility studies on valdecoxib in the presence of carriers,cosolvents, and surfactants

Enhancement of the solubility of valdecoxib was examined using a series of hydrophilic carriers (mannitol, polyethylene glycol (PEG) 4000, PEG 6000, PEG 8000, and urea), surfactants (Tween‐20, Tween‐80, and sodium lauryl sulfate [SLS]) and cosolvents (ethanol, methanol, and glycerol) at 37°C. The solubility of valdecoxib could be enhanced significantly using PEG 4000 as a carrier, ethanol as cosolvent, and SLS as a surfactant. Because the solubility of valdecoxib increased dramatically in the presence of polyethylene glycols, these are suitable dispersing agents for preparing solid dispersions containing valdecoxib. Gibbs free energy (ΔG) values were all negative for all hydrophilic carriers tested, indicating the spontaneous nature of valdecoxib solubilisation. Among the cosolvents, ethanol exhibited higher solubilization potential than methanol and glycerol. As the dielectric constant of the cosolvent–water mixtures decreased, the solubility of valdecoxib increased. Finally, SLS exerted maximum solubilization of valdecoxib when compared to Tween‐20 or Tween‐80. The crystallinity of valdecoxib was explored by X‐ray diffraction study and showed numerous crystalline peaks. Examination of surface morphology by scanning electron microscopy depicted a near spherical shape of valdecoxib with irregular surface characteristics. Drug Dev. Res. 62:41–48, 2004. © 2004 Wiley‐Liss, Inc.