Formulation and testing of methazolamide cyclodextrin eye drop solutions

Methazolamide is a carbonic anhydrase inhibitor which has been used in oral formulations to treat glaucoma. Methazolamide has a limited aqueous solubility. The effects of three different water-soluble polymers on phase-solubility diagrams of methazolamide were determined in aqueous 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) solutions. The polymers increased the stability constant (K-c) of the drug-HP beta CD complex from 28 M(-1), when no polymer was present, to 69 M(-1) when the solution contained HP beta CD and 0.1% (w/v) hydroxypropyl methylcellulose (HPMC). The solubilizing effect of the HP beta CD/HPMC combination on methazolamide was used to make aqueous eye drop solutions of methazolamide. The eye drop solutions were administrated topically to rabbits and the IOP lowering effect of the drug determined. The results show that, when formulated in aqueous HP beta CD/HPMC solutions, methazolamide is a topically active IOP lowering agent. The 1% (w/v) methazolamide solution was shown to be almost as active as Blocadren(R) (0.5% w/v timolol). These results indicate that these types of HP beta CD/HPMC low Viscosity eye drop solutions are potent delivery vehicles for topical delivery of carbonic anhydrase inhibitors to the eye.