CONICET | Buscador de Institutos y Recursos Humanos

Purpose: To evaluate the performance of 6-O-LaurylL-ascorbic acid nanostructures (coagels) as vehicles for acetazolamide in ophthalmic administration by in vitro and in vivo experimental tests. Materials and Methods: The systems of coagel + acetazolamide, were evaluated in terms of their in vitro release (dialysis membrane), permeability (isolated cornea), pharmacological effectiveness (intraocular pressure-reduction in normotensive rabbits) and their potential irritant effects. Results: The results concerning acetazolamide permeation were better when vehiculized in coagels compared to ringer solution, which was evident from the acetazolamide steady-state flux and Papp values (J= 1.43 µg/min and Papp= 3.04 cm.s1). As a consequence of this increase in permeation, the coagel-acetazolamides were more effective in lowering the intraocular pressure, according to the results obtained from the in vivo assays. Coagels loaded with 0.4 % (W/W) of acetazolamide showed a higher hypotensive effect in rabbits compared to the commercial formulation AZOPT® (brinzolamide 1%), mainly due to the prolonged effect of the former. In all cases, the intensity of irritation was time dependent. The sodium lauryl sulphate solution (2%) used as positive control produced serious injury after 30 minutes post administration. This effect caused irritation which decreased slowly and even at 180 minutes the discomfort was still considerable. However, in the case of coagels, a mild to moderate effect was observed. Conclusions: The incorporation of acetazolamide in coagels seems to improve the ocular bioavailability of this drug. Coagel-acetazolamide 0.4% showed a higher hypotensive effect, with a mild to moderate irritant effect. These systems could be administrated in human beings, although more detailed studies still need to be carried out.

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