Ricobendazole nanocrystals obtained by media milling and spray drying: Pharmacokinetic comparison with the micronized form of the drug

PAREDES, ALEJANDRO J.; CAMACHO, NAHUEL M.; SCHOFS, LAUREANO; DIB, ALICIA; ZARAZAGA, MARÍA DEL PILAR; LITTERIO, NICOLÁS; ALLEMANDI, DANIEL A.; SÁNCHEZ BRUNI, SERGIO; LANUSSE, CARLOS; PALMA, SANTIAGO D.

INTERNATIONAL JOURNAL OF PHARMACEUTICS

ELSEVIER SCIENCE BV

Año: 2020 vol. 585 p. 1 - 9

0378-5173

Helminthic infections are produced by different types of worms and affect millions of people worldwide.Benzimidazole compounds such as ricobendazole (RBZ) are widely used to treat helminthiasis. However, theirlow aqueous solubility leads to poor gastrointestinal dissolution, absorption and potential lack of efficacy. Theformulation of nanocrystals (NCs) have become the strategy of preference for hydrophobic drugs. In this work,we prepared RBZ NCs (RBZ-NCs) by an optimized combination of bead milling and spray-drying. Following thephysicochemical characterization, a comparative pharmacokinetic evaluation of RBZ-NCs was performed in dogsusing as controls a micronized powdered form of RBZ (mRBZ) and a physical mixture of drug and stabilizer 1:1(PM). The particle size of the redispersed RBZ-NCs was 181.30 ± 5.93 nm, whereas DSC, PXRD and FTIRanalyses demonstrated that the active ingredient RBZ remained physicochemically unchanged after the manufacture process. RBZ-NCs exhibited improved in vitro biopharmaceutical behaviour when compared to mRBZ.Consequently, the pharmacokinetic trial demonstrated a significant increase in the drug oral absorption, with anAUC0-∞ 1.9-fold higher in comparison to that obtained in animals treated with mRBZ. This novel formulationholds substantial potential for the development of new/alternative treatments for helminth infections both inhuman and veterinary medicine.