Development of topically effective formulations of acetazolamide using HP-beta-CD-polymer co-complexes

The myriad of side effects induced by acetazolamide (oral use), the introduction of newer topical carbonic anhydrase inhibitors (CAI's) and the advent of other antiglaucoma medications has led to a decreased interest in acetazolamide. The use of cyclodextrins to improve the solubility and bioavailability of poorly soluble drugs has however, rekindled an interest in acetazolamide (ACZ), because its poor solubility is one of the major factor responsible for its failure to show topical effectiveness. Since water soluble polymers have been reported to improve the complexing capabilities of beta-cyclodextrins, in the present study water soluble polymers like polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), hydroxypropymethylcellulose (HPMC) and the mucoadhesive polymer Carbopol 934P were incorporated into aqueous 10% w/v 2HP-beta-CD solution to improve the solubility of ACZ. The effect of these polymers on the corneal transport of 5 mg/ml (0.5% w/v) solution of ACZ in aqueous 10% 2HP-beta-CD was evaluated. The inclusion of these polymers significantly increased the solubility of ACZ from 3.43 mg/ml in aqueous 10% 2HP-beta-CD to 5.1 mg/ml (48.6%) in 0.05% PVP; 6.80 mg/ml (98.3%) in 0.05% PVA; and 6.74 mg/ml (96.5%) in 0.2% Carbopol 934P. From amongst the various polymers assessed in the study, PVA was deemed the best, based on the premise of better apparent permeability coefficient (P(app)) upon in vitro corneal permeation studies. Inspite of a large enhancement in solubility produced by Carbopol 934P, surprisingly, it could not efficiently increase the Papp.