Implantes intravítreos contendo acetazolamida para o tratamento do glaucoma: desenvolvimento e caracterização.

Abstract

Glaucoma is a chronic and multifactorial disease, characterized by typical structural changes of the optic disc and visual impairment. It affects more than 70 million individuals worldwide and is the main cause of irreversible blindness. Currently, the treatment is focused on reducing intraocular pressure, the only factor that can suffer intervention, by surgery or primarily with medications. Acetazolamide, a carbonic anhydrase inhibitor, is one of the most important drugs for this purpose, but is currently available only for systemic use, orally or intravenously, which is associated with many serious and poorly tolerated adverse effects. The development of topical formulations for the drug is very challenging, limited by its physicochemical properties, including low solubility and corneal permeation. In this context, biodegradable intravitreal implants emerged as a promising alternative to provide intraocular and prolonged release of acetazolamide, minimizing adverse effects and increasing bioavailability and adherence to the treatment. Therefore, in the present study, polylactic-co-glycolic acid-based intravitreal implants containing acetazolamide were produced by hot molding and extensively characterized. The implants were presented as white cylindrical rods, with uniform surface and length, thickness and weight of about 5.00 mm, 0.45 mm and 1.27 mg, respectively. A drug-excipient compatibility study showed no physical or chemical interactions and typical and desirable characteristics of matrix release systems. The implants were analyzed by chromatographic methods developed and validated and demonstrated a content of 230 μg/g, uniformity of content and stability for at least six months during an accelerated stability study. Sustained release of approximately 50% of the dose was observed in 42 days. In the same period of study, no signs of ocular irritation or in vitro and in vivo toxicity for the retina were observed for the devices and drugs at concentrations of up to 0.020 mmol/L. Moreover, there was significant and clinically relevant hypotensive effect for the implants in normotensive rabbits. Thus, the proposed intravitreal implants proved to be a safe and potentially effective alternative for intravitreal administration and controlled release of acetazolamide in glaucomatous patients.