The Improvement of Lorazepam Solubility by Cosolvency, Micellization and Complexation

Lorazepam is an almost water insoluble substance. This study investigated the solubilization of lorazepamdepending on media pH, cosolvents (ethanol, propylene glycol, polyethylene glycol 200 and 400), surfactants(Tween 80, Tween 20, Brij 35, sodium-cholate, sodium-deoxycholate, sodium-taurocholate) and cyclodextrins(α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin). The main objective was to find the mostsuitable method for providing good solubility of this drug and thus its formulation in a liquid dosage form.Based on the results, the changes in the pH value of the media do not lead to a greater solubility of lorazepam.Of the cosolvents used, the greatest increase in solubility of lorazepam in water was achieved with ethanol. Ofthe bile salts used, sodium taurocholate showed the best solubilization ability, while Brij 35 was the best of thenon-ionic surfactants. The solubility of lorazepam with the cyclodextrin derivative, 2-hydroxypropyl-β-cyclodextrin was better than natural cyclodextrin. Surfactants have the highest ability of solubilization oflorazepam in water