Séguy Line, Groo Anne-Claire, Goux Didier, Hennequin Didier, Malzert-Fréon Aurélie
Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), UniCaen, Normandie University, 14000 Caen, France.
Centre de Microscopie Appliquée à la biologie (CMAbio), UniCaen, Normandie University, SF4206 Icore, 14000 Caen, France.
Pharmaceutics. 2020 Nov 25;12(12):1141. doi: 10.3390/pharmaceutics12121141.
Among advanced formulation strategies, nanoemulsions are considered useful drug-delivery systems allowing to improve the solubility and the bioavailability of lipophilic drugs. To select safe excipients for nanoemulsion formulation and to discard any haemolytic potential, an in vitro miniaturized test was performed on human whole blood. From haemolysis results obtained on eighteen of the most commonly used excipients, a medium chain triglyceride, a surfactant, and a solubilizer were selected for formulation assays. Based on a design of experiments and a ternary diagram, the feasibility of nanoemulsions was determined. The composition was defined to produce monodisperse nanodroplets with a diameter of either 50 or 120 nm, and their physicochemical properties were optimized to be suitable for intravenous administration. These nanoemulsions, stable over 21 days in storage conditions, were shown to be able to encapsulate with high encapsulation efficiency and high drug loading, up to 16% (/), two water practically insoluble drug models: ibuprofen and fenofibrate. Both drugs may be released according to a modulable profile in sink conditions. Such nanoemulsions appear as a very promising and attractive strategy for the efficient early preclinical development of hydrophobic drugs.
在先进的制剂策略中，纳米乳剂被认为是有用的药物递送系统，能够提高亲脂性药物的溶解度和生物利用度。为了选择用于纳米乳剂制剂的安全辅料并排除任何溶血潜力，对人全血进行了体外小型化试验。根据对18种最常用辅料的溶血试验结果，选择了一种中链甘油三酯、一种表面活性剂和一种增溶剂进行制剂分析。基于实验设计和三元相图，确定了纳米乳剂的可行性。确定了配方以生产直径为50或120nm的单分散纳米液滴，并对其物理化学性质进行了优化，使其适合静脉给药。这些纳米乳剂在储存条件下21天内稳定，显示能够以高包封率和高载药量（高达16%，/）包封两种几乎不溶于水的药物模型：布洛芬和非诺贝特。两种药物在漏槽条件下均可根据可调节的曲线释放。这种纳米乳剂似乎是疏水性药物高效早期临床前开发的一种非常有前景和吸引力的策略。
