Details

Autor(en) / Beteiligte

• Cirilli, Roberto
• Guglielmi, Paolo
• Formica, Francesca Romana
• Casulli, Adriano
• Carradori, Simone

Titel

The sodium salt of the enantiomers of ricobendazole: Preparation, solubility and chiroptical properties

Ist Teil von

• Journal of pharmaceutical and biomedical analysis, 2017-05, Vol.139, p.1-7

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •The Na salts of the enantiomers of RBZ were obtained by a two-step process.•In the first step RBZ was resolved on a semipreparative scale by HPLC on the Chiralpak IG CSP.•In the second step the isolated enantiomers of RBZ were submit to salification by addition of NaOH.•At physiological pH the aqueous solubility of RBZ-Na was 14.49mgmL−1. Albendazole (ABZ) is a sulfanyl-benzimidazole anthelmintic drug used worldwide in the treatment and prevention of parasitic diseases in animals and humans. Following oral administration, ABZ is rapidly oxidized into the pharmacologically active chiral sulfoxide metabolite known as ricobendazole (RBZ). As its achiral precursor, RBZ shows very low intestinal absorption due to its poor solubility in water (0.06mgmL−1). To the best of our knowledge, there is no known example in human medicine of a water-soluble salt form of racemic or enantiomerically pure RBZ. In the present study, we describe in detail the preparation of the sodium (Na) salt of the enantiomers of RBZ through a two-step process: i) the multi-milligram resolution of RBZ by HPLC on the amylose-based Chiralpak IG chiral stationary phase under polar organic mode; ii) the salification of the isolated enantiomers of RBZ by reaction with sodium hydroxide solution. The spectroscopic and chiroptical properties of the RBZ-Na enantiomers were determined. Due to their unique solubility in 0.01M phosphate buffer at physiological pH (14.49mgmL−1) and the high sample throughput obtained on semipreparative separation of the non-salified form, it is potentially possible to develop new anthelmintic enantiopure formulations with improved pharmacokinetic properties and lower toxicity.