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Yalkowsky, S.H. and Roseman, T.J. (1981) Solubilization of Drugs by Co-Solvents. In: Yalkowsky, S.H., Ed., Techniques of Solubilization of Drugs, Vol. 12, Marcel Dekker Inc., New York, 91-134.

has been cited by the following article:

  • TITLE: Aqueous Solubility Enhancement of Mirtazapine: Effect of Cosolvent and Surfactant

    AUTHORS: Kenneth E. Ezealisiji, Chika J. Mbah, Patience O. Osadebe

    KEYWORDS: Mirtazapine, Cosolvency, Micellization, Aqueous Solubility

    JOURNAL NAME: Pharmacology & Pharmacy, Vol.6 No.10, October 23, 2015

    ABSTRACT: The poor aqueous solubility of drugs is a challenging problem faced by pharmaceutical scientists in drug formulation. Cosolvency and micellization techniques have been severally used to enhance the solubility of poorly aqueous soluble drugs. Mirtazapine, a tetracyclic antidepressant used for the treatment of moderate to severe depression and anxiety, has very poor aqueous solubility. The objective of the study was to investigate the effect of solubilizing agents (cosolvents and surfactants) on the aqueous solubility of mirtazapine while envisaging that any significant improvement in its aqueous solubility could contribute towards alleviating the withdrawal symptoms often associated with the drug. The solubility of mirtazapine was determined at room temperature in aqueous mixtures of cosolvents (propylene glycol and polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80 and sodium lauryl sulfate). An exponential increase in mirtazapine solubility was observed when total drug solubility in water-cosolvent system was plotted against cosolvent fraction volume. Polyethylene glycol 400 gave larger solubilization capacity (σ) when compared to propylene glycol. With the surfactants, linear relationship between the total solubility of the drug in water-surfactant mixtures and surfactant concentration was noted. Sodium lauryl sulfate showed the largest solubilization power (k) when compared to the nonionic surfactants (polysorbate 20 and polysorbate 80 respectively). A linear relationship between standard free energy and partition coefficient was also observed. The result of the study shows that aqueous solubility of mirtazapine is significantly improved by cosolvency and micellization and therefore there exists the possibility of improving the withdrawal symptoms often experienced with the drug. It also suggests that large free energy is required for drugs with high partition coefficients to permeate the biological membrane.