Abstract

A PHARMACEUTICAL STUDY OF VARIOUS ADDITIVES ON ITRACONAZOLE AS SOLUBILIZED SYSTEMS FOR OCULAR DELIVERY

Mamdouh Ghorab*, Ahmed Nassar, El-Sayed Khafagy, Shadeed Gad

Abstract

Itraconazole, a triazole antifungal agent, present significant challenges to the formulator for providing a suitable effective system for ocular delivery. The effect of different cosolvents and/or surfactants on the solubility of itraconazole shows various effects on the enhancement of itraconazole solubility. PEG 400 has the greatest solubilizing power for itraconazole and the micellar solubilization show that the aqueous solubility of itraconazole increased in a linear relationship with the concentrations of Cremophor® RH 40 shows the utmost micellar solubilization comparing with others. The effect of PEG 400- Cremophor® RH 40 combined system shows insignificant effect on improving itraconazole solubility. Phase-solubility techniques were used to assess the effect of cosolvent and/or surfactant on itraconazole complexation with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The data suggested Ap-type solubility relationships, indicating higher order complexation at higher HP-β-CD concentrations. The itraconazole-HP-β-CD complex was formed even in the presence of 10% w/v PEG 400 and/or 5% w/v Cremophor® RH 40. Although the cosolvent-surfactant combined system made the interaction of itraconazole with HP-β-CD weaker due to the competitive inclusion. The 10% w/v PEG 400-5% w/v Cremophor® RH 40 decrease the inclusion strength of HP-β-CD that upon dilution gives a larger free fraction of drug which is favorable for ocular absorption. The combination of using appropriate cosolvent and/or surfactant with the drug will be particularly useful for design of the cyclodextin-based pharmaceutical ocular formulations.

Keywords: Itraconazole; Cosolvent; Surfactant; Hydroxypropyl-?-cyclodextrin; Solubilization.