Formulation and preliminary in vivo testing of rufloxacin-cyclodextrin ophthalmic solutions

Aim of the present work was to investigate the effect of some cyclodextrins (CDs) on the solubility and ocular bioavailability of rufloxacin base (RUF), with the ultimate goal of developing an ophthalmic formulation. Phase solubility studies of RUF in pH 7.4 buffer were carried out in the presence of beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and gamma-cyclodextrin (gamma-CD). The effect of hydroxypropyl methylcellulose ( HPMC) on RUF solubility was evaluated after heating the solutions containing HP-beta-CD at 120degreesC. A significant enhancement of RUF solubility was achieved by associating the drug with CDs, particularly HP-beta-CD. This CD formed with RUF a less stable complex than that formed by beta-CD, but did not suffer the solubility limitations of the parent CD, and showed a higher solubilizing capacity than gamma-CD. Addition of 0.25% (w/v) HPMC to solutions containing HP-beta-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 the ocular bioavailability of 0.3% (w/v) RUF solubilized by HP-beta-CD was higher when compared with a 0.3% (w/v) RUF suspension used as reference.