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

PALMA, SANTIAGO DANIEL; TÁRTARA, LUIS IGNACIO; QUINTEROS, DANIELA; ALLEMANDI, DANIEL ALBERTO; LONGHI, MARCELA; GRANERO, GLADYS

JOURNAL OF CONTROLLED RELEASE

ELSEVIER SCIENCE BV

Año: 2009 p. 24 - 31

0168-3659

In 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. Formulations were also tested for their effect on the intraocular pressure (IOP) in rabbits. 1H- and 13C- NMR experiments were undertaken to verify the real inclusion of ACZ in the ACZ–HP-ß-CD-TEA multicomponent complex. The ternary system ACZ-HP-ß-CD-TEA seemed to be able to reduce IOP in about 30%. This effect was sustained for 4 h after instillation. In vitro corneal permeation studies demonstrated that the ACZ permeation was increased by means 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 the ternary system ACZ-HP-ß-CD-TEA might be a useful tool for formulating aqueous ACZ eye drop solutions.