Solubilization of tropicamide by hydroxypropyl-β-cyclodextrin and water-soluble polymers:: in vitro/in vivo studies

1% (w/v) aqueous solutions of tropicamide (TR), a poorly water-soluble mydriatic-cycloplegic drug, are usually obtained by adjusting the pH to similar to 5.0, at the expense, however, of ocular tolerance and bioavailability. The capacity of hydroxypropyl-beta -cyclodextrin (HP-beta -CD) to solubilize TR in pH 7.4 0.02 M phosphate buffer was investigated in the absence and presence of hydrophilic polymers (PVP, CMC and HPMC). Approximately 3.5% (w/v) HP-beta -CD was required to solubilize 1% (w/v) TR in pH 7.4 buffer at room temperature. The required amount was reduced to 0.9% (w/v) by heating at 120 degreesC in the presence of 0.1% (w/v) HPMC. Mydriatic activity tests in rabbits showed an improved bioavailability and maximal mydriatic response for two CD formulations, with and without HPMC, when compared to standard 1% (w/v) TR eyedrops, buffered at pH 5.0. The improved in vivo behaviour of the CD formulations are likely due to their physiological pH, resulting in a reduced irritant effect, although an effect of HP-beta -CD on corneal permeability cannot be dismissed a priori. (C) 2001 Elsevier Science B.V. All rights reserved.