Soluvec™，一种新型无溶剂水基伊维菌素配方的物理和药代动力学特征。

Physical and pharmacokinetic characterization of Soluvec™, a novel, solvent-free aqueous ivermectin formulation.

机构信息

Mountain Valley MD, 260 Edgeley Blvd - Unit 4, Concord, Ontario, L4K 3Y4, Canada.

IntrinsiChem Consulting Inc., Oakville, Ontario, L6M 4A2, Canada.

出版信息

Ther Deliv. 2023 Jun;14(6):391-399. doi: 10.4155/tde-2023-0021. Epub 2023 Aug 3.

DOI:10.4155/tde-2023-0021

PMID:37535333

Abstract

To describe application of the Quicksol™ solvent-free approach to solubilize ivermectin (IVM). Lyophilized IVM complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD) was resolubilized in aqueous polysorbate-80, generating Soluvec™. Lyophilizate was examined by Fourier-transform infrared spectroscopy and differential scanning calorimetry; Soluvec, by dynamic light scattering. Pharmacokinetics was evaluated in dogs allocated to subcutaneous (SC) or intramuscular (IM) Soluvec or oral IVM. IVM in Soluvec was tightly bound by HPβCD, forming nearly monodisperse 28 nm particles with solubility ∼2500-times that of free IVM. SC and IM Soluvec increased IVM exposure, peak IVM and extended duration of IVM exposure, versus oral dosing. The Quicksol method generated Soluvec, a concentrated aqueous parenteral IVM formulation with pharmacokinetic properties suitable for veterinary or human use.

摘要

描述 Quicksol™ 无溶剂方法在伊维菌素（IVM）溶解中的应用。将冻干的 IVM 与羟丙基-β-环糊精（HP-β-CD）络合，在聚山梨醇酯 80 水溶液中重新溶解，生成 Soluvec™。对冻干物进行傅里叶变换红外光谱和差示扫描量热法分析；对 Soluvec 进行动态光散射分析。将狗分配到皮下（SC）或肌肉内（IM）Soluvec 或口服 IVM 组，评估药代动力学。Soluvec 中的 IVM 与 HPβCD 紧密结合，形成近乎单分散的 28nm 颗粒，其溶解度比游离 IVM 高约 2500 倍。与口服给药相比，SC 和 IM Soluvec 增加了 IVM 的暴露量、峰值 IVM 和 IVM 暴露时间的延长。Quicksol 法生成了 Soluvec，这是一种浓缩的水相 IVM 注射制剂，具有适合兽医或人类使用的药代动力学特性。