Institution: | 1. Faculty of Pharmaceutical Sciences, Department of Pharmacy, University of Sao Paulo, Avenida Professor Lineu Prestes 508, Butantan, 05508-900, São Paulo, SP, Brazil;2. School of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara- Jaú Km 1, S/n, Campus Ville, 14800-903, Araraquara, SP, Brazil;3. Institute for Technological Research (IPT), Avenida Prof. Almeida Prado, 532, Butantã, 05508-280, São Paulo, SP, Brazil |
Abstract: | The glucocorticoid derivative of budesonide with a phthalimide group is a drug candidate to treat inflammatory eye diseases; nevertheless, it presents low water solubility. Drug nanocrystals have been proposed to overcome this hurdle. The development of an innovative ophthalmic anti-inflammatory nanosuspension was performed using a design space approach. We obtained the particle size reduction of this glucocorticoid derivative on a nanometer scale (approximately 165.0 nm), applying wet bead milling on a super reduced scale. The design of experiment supported the optimization of the formula evaluating the parameters that influence reducing the particle size and also allowed determining the design space. Considering the two statistical models developed and the size range obtained, we proposed that the optimized formulation for the glucocorticoid derivative nanosuspension may be 1.0 wt% glucocorticoid derivative and 0.092 wt% cetylpyridinium chloride. This formulation was characterized by the morphological, physical–chemical, and mucoadhesive in vitro test and showed potential for ophthalmic use with reduced frequency of product application, improved efficiency, and safety, which may promote better patient compliance. |