Author(s): Mooter VG, Augustigins P, Blatun N, Kinget R
In order to increase the dissolution of temazepam, solid dispersions were prepared using polyethylene glycol 6000 (PEG 6000) and polyvinylpyrrolidone K30 (PVP K30). Dispersions with PEG 6000 were prepared by fusion-cooling and co-evaporation, while dispersions containing PVP K30 were prepared by co-evaporation. In contrast to the very slow dissolution rate of pure temazepam, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as particle size reduction and decrease of the crystalline fraction of the drug. The aqueous solubility of temazepam was favoured by the presence of PEG 6000. The negative values of the Gibbs free energy and enthalpy of transfer explained the spontaneous transfer from pure water to the aqueous polymer environment. It was found that temazepam was decomposed in the presence of aqueous solutions of PVP K30 to at least two unidentified degradation products. Drug-polymer interactions in the solid state were investigated using differential scanning calorimetry, X-ray powder diffraction, and fourier-transform infrared spectroscopy. PEG 6000 gave a eutectic system in which liquid polymer could dissolve approximately 10% of temazepam. On the other hand, X-ray powder diffraction patterns and thermal analysis indicated that the drug. was in the amorphous state up to a concentration of 40% w/w when dispersed in PVP K30; the infrared spectra indicated solid state interactions between the OH of temazepam and the C=O of PVP K30.