Effect of γ-cyclodextrin on solubilization and complexation of irbesartan: influence of pH and excipients


In effort to prepare an eye drop formulation of irbesartan, the effect of γ-cyclodextrin complexation on irbesartan solubilization in aqueous solutions was investigated. The optimum cyclodextrin concentration for formation of irbesartan/cyclodextrin inclusion complex was found to be 10% (w/v) and the solubility of ionized irbesartan/γ-cyclodextrin complex (at pH 7.2) was shown to be three fold greater than that of the unionized complex (at pH 4.3). The irbesartan flux through semipermeable membranes increased with increasing γ-cyclodextrin concentration at both pH values. However, the ionized complex displayed decrease in the drug permeation coefficient with increasing cyclodextrin concentration. The effect of four pharmaceutical excipients on the cyclodextrin solubilization was investigated. EDTA, hydroxypropyl methylcellulose, and tyloxapol increased complexation efficiency of γ-cyclodextrin while benzalkonium chloride had negligible effect. The largest solubilization was observed in the eye drop vehicle that contained all four excipients in addition to γ-cyclodextrin. Dynamic light scattering measurements disclosed that excipients had impact on size of complex aggregates and consequently on the drug flux through the semipermeable membranes. Complex of irbesartan/γ-cyclodextrin was characterized by FT-IR, (1)H NMR, XRPD, and TEM techniques.

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