Improvement of the in vitro dissolution rate of mebendazole via crystallization in aqueous surfactant solutions

Abstract

The technique of crystallization from different aqueous surfactant solutions has been employed in the present study for the purpose of enhancing the solubility and dissolution rate of mebendazole (MBZ), thereby; the limited systemic availability could be improved. Crystallization was carried out using aqueous solutions of non-ionic surfactants (Tween 20, 40, 60 and 80) and ionic surfactants (sodium lauryl sulfate and cetrimide). The in vitro dissolution rates were determined for the untreated drug, the drug crystallized in water [0% surfactant] (control) and that treated with 1, 2, 3 and 4% w/v aqueous surfactant solutions. The dissolution was performed in 0.1N HCl at 37°C for 2 h. Certain factors affecting the dissolution rate enhancement namely, type and concentration of surfactant, concentration of MBZ in solution (saturated or supersaturated solution) and temperature of the crystallization medium were all investigated. The results showed higher dissolution rates for the treated samples as compared to the untreated drug with the exception of samples crystallized from cetrimide solutions which had no enhancing effect towards the dissolution rate. Samples precipitated with the non-ionic surfactants showed higher dissolution rates over those precipitated with the ionic surfactants. Moreover, samples crystallized with 3% aqueous solution of Tween 60 showed the highest dissolution rates among all the preparations. A study on the effect of aging on the dissolution rate of the sample crystallized with Tween 60 (3%) over a period of 7 months showed a slight decrease in the amount dissolved from 66.7 to 49.8% after a dissolution period of 2 h. Further evaluation was performed to study the physicochemical properties of the crystallized drug using IR spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and microscopic examination.