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

Alejandro J. Paredes, Nahuel M. Camacho, Laureano Schofs, Alicia Dib, María del Pilar Zarazaga, Nicolás Litterio, Daniel A. Allemandi, Sergio Sánchez Bruni, Carlos Lanusse, Santiago D. Palma

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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, their low aqueous solubility leads to poor gastrointestinal dissolution, absorption and potential lack of efficacy. The formulation 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 the physicochemical characterization, a comparative pharmacokinetic evaluation of RBZ-NCs was performed in dogs using 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 FTIR analyses 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 an AUC0-∞ 1.9-fold higher in comparison to that obtained in animals treated with mRBZ. This novel formulation holds substantial potential for the development of new/alternative treatments for helminth infections both in human and veterinary medicine.
Original languageEnglish
JournalInternational Journal of Pharmaceutics
Early online date05 Jun 2020
DOIs
Publication statusPublished - 30 Jul 2020

Fingerprint

Dive into the research topics of 'Ricobendazole nanocrystals obtained by media milling and spray drying: pharmacokinetic comparison with the micronized form of the drug'. Together they form a unique fingerprint.

Cite this