Nanocrystals of Novel Valerolactam-Fenbendazole Hybrid with Improved in vitro Dissolution Performance

MELIAN, MARIA ELISA; PAREDES, ALEJANDRO; MUNGUÍA, BEATRIZ; COLOBBIO, MAXIMILIANO; RAMOS, JUAN CARLOS; TEIXEIRA, RAMIRO; MANTA, EDUARDO; PALMA, SANTIAGO; FACCIO, RICARDO; DOMÍNGUEZ, LAURA

AAPS PHARMSCITECH

SPRINGER

Año: 2020 vol. 21

1530-9932

alero-fenbendazole (VAL-FBZ) is a novel hybrid compound with in vitro anthelmintic activity, designed and synthesized to address the global problem of resistance to anthelmintic compounds. This new molecule derives from fenbendazole (FBZ), a well-known commercially available benzimidazole used in veterinary medicine despite its poor water solubility. In this work, we report for the first time a strategy to solve the solubility problems of FBZ and VAL-FBZ by means of self-dispersible nanocrystals (SDNC). Nanocrystals were prepared by media milling followed by a spray-drying step, and a comprehensive and exhaustive structural and physicochemical characterization was carried out, in order to understand the systems and their behavior. The formulation poloxamer 188 (P188):FBZ 1:1 turned out with the best process yield (53%) and re-dispersability properties, particle size average of 258 nm, and polydispersity index of 0.2 after redispersion in water. The dissolution profile showed a markedl