Transbuccal delivery of benznidazole associated with monoterpenes: permeation studies and mechanistic insights.,European Journal of Pharmaceutical Sciences

当前位置： X-MOL 学术 › Eur. J. Pharm. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Transbuccal delivery of benznidazole associated with monoterpenes: permeation studies and mechanistic insights.
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2019-12-05 , DOI: 10.1016/j.ejps.2019.105177
Beatriz Ribeiro Amaral ₁ , Débora Fretes Argenta ₁ , Roselene Kroth ₁ , Thiago Caon ₁

Affiliation

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.

中文翻译：

经颊腔输送苯并硝唑与单萜类化合物：渗透研究和机理见解。

在大多数流行国家，苯并咪唑（BZN）是目前可用于治疗恰加斯病的唯一药物。口服给药时，由于其广泛的肝代谢，因此需要高剂量，并且其毒性是停药的主要原因。由于这些并发症，对经颊颊给予BZN进行了研究。该途径避免了肝脏的首过代谢，并具有高通透性，可直接进入体循环。用纯丁子香酚，香芹酚或柠檬烯预处理后，将BZN应用于猪颊粘膜。进行了热分析（DSC）和光谱分析（FT-IR），以研究药物吸收增强的机制。用丁子香酚预处理后，BZN的渗透系数值分别提高了2.6倍，2.9倍和4.9倍，香芹酚和柠檬烯分别。相应地，预处理样品中的滞后时间缩短了。DSC和FT-IR分析表明BZN通过颊粘膜的转运与log P和单萜的大小有关。柠檬烯是最有效的吸收促进剂，有助于与颊上皮的非极性区域发生更大的相互作用。总体而言，BZN已显示可通过颊途径有效转运，但应进行体内药代动力学研究以证实这些发现。有助于与颊上皮非极性区域的相互作用。总体而言，BZN已显示可通过颊途径有效转运，但应进行体内药代动力学研究以证实这些发现。有助于与颊上皮非极性区域的相互作用。总体而言，BZN已显示可通过颊途径有效转运，但应进行体内药代动力学研究以证实这些发现。

更新日期：2019-12-05

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11