2-HYDROXYPROPYL-BETA-CYCLODEXTRIN IN TOPICAL CARBONIC-ANHYDRASE INHIBITOR FORMULATIONS

The effect of 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) on the pe rmeation of acetazolamide through semi-permeable membrane and the topi cal delivery of acetazolamide and ethoxyzolamide was investigated. Bot h the Free drug and the drug-HP beta CD complex permeate a semi-permea ble cellophane membrane, but the free drug molecules permeate the memb rane at a rate about 24 times faster than the drug-HP beta CD complex. Maximum acetazolamide penetration was obtained when just enough HP be ta CD was used to keep all acetazolamide in solution. Only insignifica nt amounts of HP beta CD are able to permeate tight biological barrier s like the eye cornea. Our results indicate that HP beta CD increases the ocular bioavailability of acetazolamide by keeping the acetazolami de molecules in solution and increasing their availability at the surf ace of the corneal barrier without penetrating the barrier itself In v ivo experiments in rabbits showed that topically applied aqueous 1% ac etazolamide low viscosity eye-drop solution had notable but somewhat l ess IOP lowering effect than Blocadren(R).