Technische Universität Braunschweig, Institut für Pharmazeutische Technologie, Mendelssohnstraße 1 & Zentrum für Pharmaverfahrenstechnik (PVZ), Franz-Liszt-Straße 35a, 38106 Braunschweig, Germany.
Technische Universität Braunschweig, Institut für Pharmazeutische Technologie, Mendelssohnstraße 1 & Zentrum für Pharmaverfahrenstechnik (PVZ), Franz-Liszt-Straße 35a, 38106 Braunschweig, Germany.
Eur J Pharm Biopharm. 2018 May;126:123-131. doi: 10.1016/j.ejpb.2017.05.009. Epub 2017 May 18.
Passive drug loading can be used to effectively identify suitable colloidal lipid carrier systems for poorly water-soluble drugs. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles. Until now, the passive loading mechanism is unknown, which complicates reliable routine use. In this work, the influence of drug characteristics on the course of passive loading was investigated systematically varying drug surface area and drug solubility. Fenofibrate and flufenamic acid were used as model drugs; the carrier system was a trimyristin nanodispersion. Loading progress was analyzed by UV spectroscopy or by a novel method based on differential scanning calorimetry. While increasing drug solubility by micelle incorporation did not speed up passive loading, a large drug surface area and high water solubility were key parameters for fast loading. Since both factors are crucial in drug dissolution as described by the Noyes-Whitney equation, these findings point to a dissolution-diffusion-based passive loading mechanism. Accordingly, passive loading also occurred when drug and carrier particles were separated by a dialysis membrane. Knowledge of the loading mechanism allows optimizing the conditions for future passive loading studies and assessing the limitations of the method.
被动载药可用于有效鉴定适用于疏水性药物的胶体脂质载体系统。该方法包括将预形成的载体系统与药物粉末孵育，然后测定载体颗粒的载药量。到目前为止，被动载药机制尚不清楚，这给可靠的常规应用带来了困难。在这项工作中，通过改变药物表面积和药物溶解度，系统地研究了药物特性对被动载药过程的影响。非诺贝特和氟芬那酸被用作模型药物；载体系统是三软脂酰甘油纳米分散体。通过紫外光谱或基于差示扫描量热法的新方法分析载药进展。虽然通过胶束包合增加药物溶解度并不能加快被动载药，但大的药物表面积和高的水溶性是快速载药的关键参数。由于这两个因素在 Noyes-Whitney 方程描述的药物溶解中都很重要，因此这些发现表明存在基于溶解-扩散的被动载药机制。因此，即使药物和载体颗粒被透析膜隔开，也会发生被动载药。对载药机制的了解可优化未来被动载药研究的条件，并评估该方法的局限性。
