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

The effect of 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) on the permeation of acetazolamide through semi-permeable membrane and the topical delivery of acetazolamide and ethoxyzolamide was investigated. Both the Free drug and the drug-HP beta CD complex permeate a semi-permeable cellophane membrane, but the free drug molecules permeate the membrane at a rate about 24 times faster than the drug-HP beta CD complex. Maximum acetazolamide penetration was obtained when just enough HP beta CD was used to keep all acetazolamide in solution. Only insignificant amounts of HP beta CD are able to permeate tight biological barriers like the eye cornea. Our results indicate that HP beta CD increases the ocular bioavailability of acetazolamide by keeping the acetazolamide molecules in solution and increasing their availability at the surface of the corneal barrier without penetrating the barrier itself In vivo experiments in rabbits showed that topically applied aqueous 1% acetazolamide low viscosity eye-drop solution had notable but somewhat less IOP lowering effect than Blocadren(R).