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.
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