Physicochemical aspects of drug release. XIII. The effect of sodium dodecyl sulphate additions on the structure and dissolution of a drug in solid dispersions

Abstract

Solid dispersions of the sparingly soluble drug griseofulvin were prepared by the melting method with polyethylene glycol (PEG) 3000 as a carrier. The anionic surfactant sodium dodecyl sulphate (SDS) was incorporated during the preparation, in order to study the effect on incorporated state and dissolution of the drug. Dissolution rate measurements were performed according to USP XXI (paddle method) on dispersion particles in media of pure distilled water or distilled water with different concentrations of SDS, all below the critical micelle concentration. For solid dispersions without SDS incorporated, the dissolution rate was reduced with an increase in griseofulvin content. When SDS was added to the medium the dissolution rate increased in proportion to the concentration of SDS. These results support the assumption that wetting the dispersion particles is important in the dissolution process of these systems. The fastest drug dissolution was obtained for dispersions incorporating SDS. In dispersions containing 1% w/w SDS, 90% of the griseofulvin was dissolved within 2 min, independent of drug concentration and dissolution medium. It was possible to determine the relative amounts of each phase using the X-ray diffraction method. It was observed that in solid dispersions without SDS incorporated, both the pure griseofulvin phase and the pure PEG phase were present. In samples with SDS incorporated the phase composition changed. A large amount of griseofulvin was dissolved in the PEG/SDS structure forming a solid solution. In solid dispersions of 3 and 10% w/w griseofulvin with 1 and 2% w/w SDS incorporated, respectively, no pure griseofulvin phase was seen and the solid solution of griseofulvin in the PEG/SDS structure was the only phase appearing. The heat of fusion values, obtained by DSC, supported the idea of a change in the phase composition in the systems with the incorporation of SDS.