The Improvement of Lorazepam Solubility by Cosolvency, Micellization and Complexation

Jasmina Hadžiabdić, Alisa Elezovic, Belma Imamovic, Ervina Becic

Abstract


Lorazepam is an almost water insoluble substance. This study investigated the solubilization of lorazepam depending 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, -cyclodextrin and 2-hydroxypropyl-β-cyclodextrin). The main objective was to find the most suitable 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. Of the bile salts used, sodium taurocholate showed the best solubilization ability, while Brij 35 was the best of the non-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 of lorazepam in water.

Keywords


solubility enhancement, lorazepam, pH, cosolvents, surfactants, cyclodextrins

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