Institute of Pharmaceutical Technology and Biopharmacy, University Muenster, Corrensstraße 48, 48149 Muenster, Germany.
Bayer AG, Process Technologies, Chempark, Building E41, 51368 Leverkusen, Germany.
Int J Pharm. 2024 Sep 5;662:124491. doi: 10.1016/j.ijpharm.2024.124491. Epub 2024 Jul 18.
The nanoparticle albumin bound™ (nab™) technology generally offers great potential for the formulation of poorly water-soluble drugs as albumin-stabilized nanosuspensions for intravenous use while avoiding solubilizers and cross-linking agents. The nab™ technology is a three-step process consisting of emulsification, high-pressure homogenization and solvent evaporation. Within this work, a screening approach was developed to predict whether active pharmaceutical ingredients are suitable for nab™ formulations. A design of experiments approach was used to investigate the effects of ultrasonic homogenization on an albumin-stabilized itraconazole nanosuspension. Based on this, a screening platform was developed, and subsequently evaluated and applied to a selection of poorly water-soluble drugs. The screening process to produce albumin-stabilized nanosuspensions consists of two process steps: Ultrasonic treatment, which combined emulsification and homogenization, followed by solvent evaporation. The results of the screening process were fully transferable to the standard three-step process of nab™ technology. In addition, based on drug screening, drug properties were highlighted that are important for the development of nab™ formulations. All in all, the nab™ technology is a promising but not universal formulation platform for poorly water-soluble drugs. Nevertheless, for some poorly soluble drugs it offers a valuable approach for the formulation of nanosuspensions for intravenous use.
纳米白蛋白结合（nab）技术通常为将亲脂性药物制成白蛋白稳定的纳米混悬剂用于静脉注射提供了巨大的潜力，同时避免使用增溶剂和交联剂。nab 技术是一个由乳化、高压匀质和溶剂蒸发三个步骤组成的过程。在这项工作中，开发了一种筛选方法来预测原料药是否适合 nab 制剂。采用实验设计方法研究了超声匀质对白蛋白稳定的伊曲康唑纳米混悬剂的影响。在此基础上，开发了一个筛选平台，并对一系列疏水性药物进行了评估和应用。制备白蛋白稳定的纳米混悬剂的筛选过程包括两个工艺步骤：超声处理，它结合了乳化和匀质，然后进行溶剂蒸发。筛选过程的结果可以完全转移到 nab 技术的标准三步过程中。此外，基于药物筛选，突出了对 nab 制剂开发重要的药物性质。总的来说，nab 技术是一种有前途但并非普遍适用于疏水性药物的制剂平台。然而，对于一些疏水性药物，它为静脉注射用纳米混悬剂的制剂提供了一种有价值的方法。
