The effect of dry mixing on the apparent solubility of hydrophobic, sparingly soluble drugs.

The effect of dry mixing on the apparent solubility of two hydrophobic sparingly soluble drugs was studied. The materials were mixed with NaCl or glass beads in a Turbula mixer and the changes in solubility were monitored. It was shown that dry mixing caused an increase in the apparent solubility of test materials. It is suggested that the surfaces of the particles become activated and disordered during the dry mixing process. This peripheral surface disorder appears to be responsible for the increase in solubility. It was also shown that apparent solubility of the drugs after dry mixing was strongly dependent on the amount of drug added to the solvent, increasing with increasing concentrations. A plateau was established gradually at higher proportions of drug to solvent. Finally the applicability of the solubility model described by Mosharraf et al. (1999) [Mosharraf, M., Sebhatu, T., Nyström, C., 1999. The effects of disordered structure on solubility and dissolution rates of hydrophilic, sparingly soluble drugs. Int. J. Pharm. 177, 29-51] to the solubility behaviour of the hydrophobic sparingly soluble drugs tested in this study was confirmed. The results suggested that the equilibrium solubility plateau levels of a disordered material are determined by the degree and the location of disorder on the individual particles.