PHASE-EQUILIBRIA IN DRUG-POLYMER-SURFACTANT SYSTEMS

Solid dispersions of griseofulvin were prepared by the melting method with polyethylene. glycols (PEGs) of molecular weights 3000, 6000 and 20 000 as carriers, with or without the incorporation of the anionic surfactant sodium dodecyl sulphate (SDS). The state diagrams for griseofulvin and different PEGs with SDS added and the state diagram with PEG 6000 and griseofulvin alone were obtained using X-ray powder diffraction and differential scanning calorimetry. Solid solutions of griseofulvin in both pure polyethylene glycol and polyethylene glycol with SDS incorporated were formed. The pure polymers dissolved less than 3% w/w griseofulvin. When SDS was incorporated in the polyethylene glycols, the solid solubility of griseofulvin increased to 40% w/w in PEG 6000 and to 25% w/w in PEG 3000 and PEG 20 000. The solid solutions of griseofulvin in PEC with SDS incorporated melted close to the melting temperature of the pure PEG phases. Their heat of fusion values differed significantly from those of the solid dispersions. The effect of different alkali dodecyl sulphates, LiDS, SDS and KDS, forming solid solutions with PEG 3000 and griseofulvin was analysed using oscillating differential scanning calorimetry in the temperature interval -60 degrees C to 80 degrees C. The thermal behaviour of the LiDS-containing solid solution was different from those of SDS- and KDS-containing compounds, with respect to both the C-p (reversible) component and the kinetic (irreversible) component. The enthalpy changes exposed by the Delta H-Cp and Delta H-K components were extremely sample-dependent, whereas the conventional Delta H values were constant.