Transbuccal delivery of benznidazole associated with monoterpenes: permeation studies and mechanistic insights

• Published in: European journal of pharmaceutical sciences 2020-02, Vol.143, p.105177-105177, Article 105177
• Main Authors: Amaral, Beatriz Ribeiro, Argenta, Débora Fretes, Kroth, Roselene, Caon, Thiago
• Format: Article
• Language: English
• Subjects: Absorption enhancers; Benznidazole; Buccal permeability; Monoterpenes
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105177

Benznidazole (BZN) represents the only drug currently available for the treatment of Chagas disease in most endemic countries. When administered orally, high doses are required due to its extensive hepatic metabolism and its toxicity represents the main reason for treatment withdrawals. Because of these complications, transbuccal administration of BZN was investigated. This route avoids the first-pass hepatic metabolism and presents high permeability, with direct access to the systemic circulation. BZN was applied on porcine buccal mucosa after pretreatment with pure eugenol, carvacrol or limonene. Thermal (DSC) and spectroscopic (FT-IR) analyzes were performed to investigate the mechanisms of drug absorption enhancement. The permeability coefficient values of BZN increased 2.6, 2.9 and 4.9-fold after pretreatment with eugenol, carvacrol and limonene, respectively. The lag time, in turn, was shortened in the pretreated samples. The DSC and FT-IR analyzes suggested that transport of BZN through the buccal mucosa is associated with log P and size of monoterpenes. Limonene, the most effective absorption enhancer, contributed to greater interaction with non-polar domains of the buccal epithelium. Overall, BZN showed to be efficiently transported through the buccal route, but in vivo pharmacokinetic studies should be performed to confirm these findings. [Display omitted]