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开发一种安全的小儿液体自微乳化给药系统用于治疗片形吸虫病的三氯苯达唑。

Development of a safe pediatric liquisolid self-nanoemulsifying system of triclabendazole for the treatment of fascioliasis.

机构信息

College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.

College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.

出版信息

Int J Pharm. 2022 Oct 15;626:122163. doi: 10.1016/j.ijpharm.2022.122163. Epub 2022 Sep 5.

DOI:10.1016/j.ijpharm.2022.122163
PMID:36067920
Abstract

Fascioliasis, a common parasitic infection observed in the pediatric patient population, is a leading cause of concern in countries with poor/unhealthy water resources. To treat this condition first line agent such as triclabendazole (TBZ) has been the choice therapy. However, there is a major hurdle in exploiting TBZ. Characterized with poor aqueous solubility (0.1 mg/L), its solubility has been the rate limiting factor, rendering requirement of large doses of TBZ. To address the same, the focus of the current study was to develop a self-nano emulsifying drug delivery system (TBZ-SNEDDS) for TBZ and developing dose customizable pediatric dispersible color-coded tablets. TBZ-SNEDDS were successfully formulated by using Kolliphor®EL, as a surfactant, a lipid phase of medium chain triglyceride and α-tocopherol in the ratio of (1:1), with dimethylacetamide (DMA) as a solvent. It was observed during in vitro release studies that there was a significant effect of fed conditions on the rate of TBZ release from the formulation. greater than 85 % TBZ was observed to release in fed conditions in comparison to fasted conditions. As currently TBZ is prescribed on a weight-based dosage regimen, it is imperative to develop a dose-customizable fast dissolving pediatric formulation. Hence, TBZ-SNEDDS could prove to be pivotal in helping countless children around the world in desperate conditions to get cheap yet effective therapy.

摘要

肝片形吸虫病是一种常见的寄生虫感染,在水资源较差/不健康的国家是一个主要的关注点。治疗这种疾病的一线药物如三氯苯达唑(TBZ)一直是首选治疗方法。然而,在开发 TBZ 时存在一个主要障碍。其水溶性差(0.1mg/L),溶解度是限速因素,需要使用大剂量的 TBZ。为了解决这个问题,目前的研究重点是开发 TBZ 的自微乳给药系统(TBZ-SNEDDS),并开发可定制剂量的儿科分散片。通过使用 Kolliphor®EL 作为表面活性剂、中链甘油三酯和 α-生育酚的脂质相(1:1),并使用二甲基乙酰胺(DMA)作为溶剂,成功地制备了 TBZ-SNEDDS。在体外释放研究中观察到,给食条件对制剂中 TBZ 释放速率有显著影响。与空腹条件相比,在给食条件下,超过 85%的 TBZ 被释放。由于目前 TBZ 是根据体重剂量方案开处方的,因此开发一种可定制剂量的快速溶解儿科制剂势在必行。因此,TBZ-SNEDDS 可以帮助世界上无数处于困境中的儿童获得廉价而有效的治疗。

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