Interaction of polyethylene glycols with larazepam

The influence of variation of the molecular weight and the proportions of polyethylene glycols (PEGs) on the solubility and dissolution behavior of lorazepam was investigated. The equilibrium solubility of of lorazepam in presence of different concentrations of PEG 1540 and PEG 10 000 was determined at 25 degrees C. The influence of temperature on the equilibrium solubility of lorazepam in presence of PEGs was studied in each case and the thermodynamic functions were calculated. Solid dispersions were prepared by the solvent evaporation technique. It was found that PEGs favored the aqueous solubility of lorazepam, and the effect is increased as the concentration of the polymers is increased. The effect of PEGs on the solubility of lorazepam in water is more pronounced with PEG 1540 rather than PEG 10 000. The positive entropy values and the endothermic nature of the heat of solution, tend to rule out a hydrogen bond formation and further indicate that the solubility of lorazepam in PEG solutions was entropic rather than electrostatic in nature. Enhancement of dissolution of lorazepam was observed for all solid dispersion, and higher dissolution was obtained as the molecular weight of PEG was decreased and as the weight fraction of PEG was increased up to 1 : 2 drug-polymer ratio. Differential scanning calorimetry studies exclude the presence of crystalline drug in the dispersions. The high solvent power of PEGs for lorazepam is indicative for the high activity of the drug in the polymer solution and hence greater solution.