DEVELOPMENT OF TRIAMCINOLONE ACETONIDE NANOCRYSTALS FOR OCULAR ADMINISTRATION

AWDE ALFONSO, HAMOUDI G.; FORMICA, MARÍA L.; ALEJANDRO JAVIER PAREDES; PALMA, SANTIAGO D.

Cordóba

Congreso; ASOCIACION ARGENTINA DE FARMACOLOGIA EXPERIMENTAL LIII REUNION ANUAL; 2021

ASOCIACION ARGENTINA DE FARMACOLOGIA EXPERIMENTAL

Objectives: Triamcinolone acetonide (TA) is a powerful anti-inflammatory drug, used in the treatment of inflammatory ocular disorders. Poor drug solubility and ocular anatomical barriers hinder an optimum therapy. The principal problems related to the use of injectable approved formulations of TA include particle size (>1µm), which can hinder the administration, and also the presence of excipients as preservatives, which can generate cell damage. The purpose of this work was to obtain a formulation based on triamcinolone acetonide nanocrystals (TA-NCs) to improve ocular corticosteroid therapy.Material and Methods: The microsphere assisted nanomilling (MAN) followed by spray-drying (SPA) techniques were used to obtain dried TA-NCs, which were characterized by studies of dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), thermal analysis, X-ray diffraction (XRD), and Electron microscopy (SEM). Preliminary studies of anti-inflammatory efficacy of a suspension of dispersable TA-NCs via subconjunctival route (n=5) were carried out in an endotoxin-induced uveitis (EIU) rabbit model and compared with a control group (normal saline solution). Results: Dispersable TA-NCs presented an average particle size of (266±77) nm; a narrow size distribution and zeta potential of (-27±1) mV, which remained stable during 30 days under storage conditions at 4 °C. TA-NCs showed uniform and spherical morphology (SEM). FTIR and XRD spectra showed no apparent chemical and crystallinity changes, while no apparent thermal changes were revealed by thermal analysis. The subconjunctival administration of TA-NCs in albino male white rabbits did not show clinical signs of ocular damage. In vivo preliminary studies showed that dispersable TA-NCs treatment alleviated the inflammatory response in the anterior chamber and iris in EUI rabbit eyes. Conclusion: Dispersable TA-NCs are a promising approach to obtain a novel nanometric TA formulation for ocular disorders.