Formulation and preliminary in vivo Testing of Rufloxacin-Cyclodextrin ophthalmic solutions

Aim of the present work was to investigate the effect of somecyclodextrins (CDs) on the solubility and ocular bioavailability of rufloxacin base (RUF), with theultimate goal of developing an ophthalmic formulation. Phase solubility studies of RUF inpH 7.4 buffer were carried out in the presence of β-cyclodextrin (β-CD),hydroxypropyl-β-cyclodextrin (HP-β-CD) and γ-cyclodextrin(γ-CD). The effect of hydroxypropyl methylcellulose (HPMC) on RUF solubility was evaluated after heating the solutionscontaining HP-β-CD at 120 °C. A significant enhancement of RUF solubility was achieved by associatingthe drug with CDs, particularly HP-β-CD. This CD formed with RUF a less stablecomplex than that formed by β-CD, but did not suffer the solubility limitations ofthe parent CD, and showed a higher solubilizing capacity than γ-CD. Addition of 0.25%(w/v) HPMC to solutions containing HP-β-CD increased the solubilizing effect of this CD,thus allowing reduction of the amount necessary for solubilization of 0.3% (w/v) RUF. Preliminary pharmacokinetic data in rabbits indicated that theocular bioavailability of 0.3% (w/v) RUF solubilized by HP-β-CD was higher when compared witha 0.3% (w/v) RUF suspension used as reference.