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Luis I. Tartara, Santiago D. Palma, Daniela A. Quinteros, Marcela R. Longhi, Daniel A. Allemandi, Gladys E. Granero; Rediscovering An "Old Drug": Topical Application Of Acetazolamide Using A Ternary Complex With Hp-ß-cd And Tea. Invest. Ophthalmol. Vis. Sci. 2012;53(14):466.
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In order to enhance the ocular bioavailability of acetazolamide (ACZ), a novel liquid formulation based on a multicomponent complex with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and triethanolamine (TEA) was prepared. In vitro e In vivo performance of this formulation was assayed in rabbits.
The background of the design of this formulation was the interaction between the components of the ternary complex. 1H- and 13C- NMR experiments were undertaken to verify the real inclusion of ACZ in theACZ-HP-ß-CD-TEA complex. The biopharmaceutical performance of the formulation was evaluated by mean of In vitro corneal permeation and the In vivo effect on the intraocular pressure (IOP). The marketed ophthalmic solution AZOPT® (1% w/v brinzolamide) was also included in the assays for comparison.
The ternary system ACZ-HP-ß-CD-TEA seemed to be able to reduce IOP in about 30% after two hours. This effect was sustained for four hours after instillation. In vitro corneal permeation studies demonstrated that the ACZ permeation was increased as consequence of the multicomponent complex formation. RMN experiments indicated that TEA can weaken the association between ACZ and HP-ß-CD increasing the drug ocular hypotensive effect by increasing rate and extent of drug dissolution; due to the relative stability of the ternary ACZ-HP-ß-CD-TEA system. All formulations, including the commercial product, were considered practically non-irritant.
These results indicate that this new strategy for ACZ formulation could improve the treatment of IOP. The new formulation thus obtained was to be able to facilitate ACZ corneal permeation and showedappreciable pharmacological activity.
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