An efficient ternary complex of acetazolamide with HP-ß-CD and TEA for topical ocular administration

SANTIAGO D. PALMA; LUIS I. TARTARA; DANIELA QUINTEROS; DANIEL A. ALLEMANDI; MARCELA R. LONGHI; GLADYS E. GRANERO

ELSEVIER SCIENCE BV

Año: 2009 vol. 138 p. 24 - 24

n order to enhance the ocular bioavailability of acetazolamide (ACZ), a multicomponent complex with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and triethanolamine (TEA) was prepared to be applied topically. In vitro corneal permeation across isolated rabbit cornea of proposed ACZ formulations and the marketed AZOPT® formulation (1%w/v brinzolamide)was studied. Formulationswere also tested for their effect on the intraocular pressure (IOP) in rabbits. 1H- and 13C-NMRexperimentswere undertaken to verify the real inclusion of ACZ in the ACZ?HP-ß-CD?TEAmulticomponent complex. The binding of ACZ to HP-ß-CD in the presence of TEA is described. The increase of TEA concentration decreases the apparent equilibrium constant for the ACZ?HP-ß-CD complex. The ternary systemACZ?HP-ß-CD?TEA seemed to be able to reduce IOP in about 30%. This effectwas sustained for 4 h after instillation. In vitro corneal permeation studies demonstrated that the ACZ permeation was increased. RMN experiments indicate