The anti-inflammatory nanocrystals development of phthalimide associated with budesonide hybrid compound for ophthalmic application

• Autor(a) principal: Maria Christina Camasmie Peters
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
• Texto Completo: https://doi.org/10.11606/D.9.2020.tde-05072021-163351

Glucocorticoids are widely used for the treatment of eye inflammation followed or not by infection. Although effective, this class of drugs has significant adverse effects such as increased intraocular pressure and cataracts. Thus, the development of an innovative drug with greater efficacy and safety for the treatment of ophthalmic inflammation is of fundamental importance. The glucocorticoid derivative synthesized by molecular hybridization of phthalimide associated with budesonide revealed anti-inflammatory activity. Furthermore, this drug candidate was designed to eliminate the undesirable adverse effects of glucocorticoids. However, this compound has low water solubility, limiting its bioavailability for ocular use. In this sense, drug nanocrystals allow overcome this challenge by reducing the radius of the particles with a consequent increase in the surface area. This high increase in the ratio between the area and the volume of the particle allows the increase in the saturation solubility and mucoadhesiveness of the drug candidate. Moreover, the development of pharmaceutical products must be carried out using a systematic approach that allows revealing interactions or effects between components of the formula and the critical process parameters. Thus, in the present study, design of experiment (DoE) was used to develop nanosuspension of this glucocorticoid derivative. The reduction in the particle size of the drug candidate was carried out by applying super small scale wet bead milling, giving rise to particles with an average size equal to 165.0 nm. The application of the statistical tool allowed formula optimization. The parameters that influence the particle size reduction were determined: stirring speed and the surfactant concentration. Besides, the statistical approach revealed the interaction between the types of surfactants (synergistic stabilizing action). Among the surfactants tested, those that promoted the greatest reduction in particle size were cationic: benzalkonium chloride (BAK) or cetylpyridinium chloride (CPC). These usually do not perform this function in conventional ophthalmic preparations. In general, they are used as antimicrobial preservatives in multi-dose preparations. The optimized formulation presented the following composition: 1.0 % (w/w) of glucocorticoid derivative and 0.092 % (w/w) of cetylpyridinium chloride. This nanosuspension was evaluated for its morphology, physicochemical characteristics, and in vitro mucoadhesiveness test. Therefore, the present study allowed the development of an innovative product with potential applications in the treatment of eye inflammations.