A recombinant smart elastin-like tetrablock-copolymer for the controlled release of acetazolamide

FERNÁNDEZ COLINO, A.; CID, A. G.; BERMUDEZ, J. M.; GONZO, E. E.; ARIAS, J.

Córdoba

Otro; 3° Reunión Internacional de Ciencias Farmacéuticas -RICiFa 2014; 2014

Acetazolamide (AZM) is used for the treatment of glaucoma. Topical administration is the most common route for ophthalmic medications, but it presents some limitations, such as the short precorneal residence time and the poor bioavailability of most eye-drop solutions. Several approaches to increase the ocular bioavailability of drugs are subject of research. The aim of this work was to evaluate the ability of a recombinant smart elastin-like tetrablock-copolymer (E50I60)2 to release AZM for potential use as a drug delivery system platform. The influence of the medium (NaCl 0.9 or Dextrose 5%) on the release profile of AZM from the tetrablock hydrogel was investigated at physiological temperatures over a period of 6 days, and the release kinetics were determined using the Korsmeyer kinetic model. The results showed that AZM release was sustained over the period of time studied, with a visible absence of burst release at the initial time-points. The release kinetics of AZM from tetrablock hydrogels were markedly influenced by the release medium, with rate constants, K, of 5.19 and 1.03 for NaCl and dextrose respectively. Although similar quantities of released AZM were detected after 6 days (cumulative release of 79% in NaCl, and 70% for dextrose), the shape of the released profile was totally different, pointing out the differences in the drug delivery mechanism. The data for the release profile of AZM from the hydrogel on dextrose solution fitted an anomalous (non-Fickian) mode of diffusion (n= 0.84), thus suggesting a combination of pure AZM diffusion and polymer relaxation/swelling mechanisms. On the other hand, when the medium was NaCl the release profile followed a Fickian diffusion model (n=0.58), evidencing a pure diffusion mechanism. In conclusion, the dispersing medium influences the released profile of AZM and tetrablock hydrogel has great potential for use as a component of ophthalmic pharmaceutical formulations.