A PROMISING ACETAZOLAMIDE NANOCRYSTALS FORMULATION FOR GLAUCOMA TREATMENT.

AWDE ALFONSO, HAMOUDI G.; FORMICA, MARÍA L.; TÁRTARA, LUIS IGNACIO; PAREDES, ALEJANDRO J.; PALMA, SANTIAGO D.

Rosario

Congreso; 7MA REUNIÓN INTERNACIONAL DE CIENCIAS FARMACÉUTICAS; 2023

Glaucoma is a multifactorial, progressive, and neurodegenerative disease, characterized by increased high intraocular pressure (IOP). Acetazolamide (ACZ) is an inhibitor of the enzyme carbonic anhydrase that controls the secretion of fluids such as aqueous humor, reducing the IOP. However, it must be administered orally and high doses are required due to its poor permeability. In this study, an ocular formulation based on acetazolamide nanocrystals (ACZ-NCs) was proposed to improve glaucoma treatment.For this goal, the wet bead milling technique was used to obtain a nanosuspension of AZM-NCs, followed by a spray drying process to obtain dried dispersible ACZ-NCs. A mixture design was carried out to study the optimum drug: stabilizer proportion, and subsequently drug nanosuspension was spray-dried. ACZ-NCs were characterized in terms of size, polydispersity index (PDI), zeta potential (ZP), morphological analysis by electronic microscopy, thermal analysis, FTIR and XRD. The in vivo ocular tolerability and IOP reduction were evaluated in normotensive male albino white rabbits (n=9) via eye drop instillation.Dispersible ACZ-NCs showed an average size of (303,3±11,07) nm, PDI of (0,135±0,0120) and ZP of (-29± 0,97) mV, which remained stable until 45 days stored as a dried powder at room temperature. FTIR and XRD spectra showed no apparent chemical and crystallinity changes, while no apparent thermal changes were revealed by thermal analysis. Furthermore, ACZ-NCs showed high solubility and presented spherical shapes with a rougher surface. In turn, ACZ-NCs presented higher mucin adhesion degrees compared to normal-sized ACZ powder. Finally, in vivo evaluation showed a significant IOP decrease in the group of animals treated with dispersible ACZ-NCs compared with the groups of animals treated with a suspension of ACZ powder as the normal saline solution (control).Thus, dispersible ACZ-NCs are a promising approach to achieving a simple eye drop formulation for the treatment of glaucoma.