title: Effect of γ-cyclodextrin on solubilization and complexation of irbesartan: influence of pH and excipients.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland; Faculty of Pharmacy, Siam University, 38 Petkasem Road, Phasicharoen, Bangkae, Bangkok 10160, Thailand.
authors.forename: Chutimon
authors.initials: C
authors.lastname: Muankaew
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok 10330, Thailand.
authors.forename: Phatsawee
authors.initials: P
authors.lastname: Jansook
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, National University Hospital, Eiríksgata 37, IS-101 Reykjavík, Iceland.
authors.forename: Einar
authors.initials: E
authors.lastname: Stefánsson
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland. Electronic address: thorstlo@hi.is.
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D000077405:Irbesartan; D015394:Molecular Structure; D012995:Solubility; D013777:Tetrazoles / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D001713:Biphenyl Compounds; D005079:Excipients; D013777:Tetrazoles; D047408:gamma-Cyclodextrins; D000077405:Irbesartan; C023792:gamma-cyclodextrin
keywords: Complexation; Excipient; Irbesartan; Solubilization; pH; γ-Cyclodextrin