Liu Tao, Müller Rainer H, Möschwitzer Jan P
Department of Pharmaceutical Engineering, Qingdao University of Science and Technology, Qingdao, China.
Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Freie Universität Berlin, Berlin, Germany.
AAPS PharmSciTech. 2017 Jul;18(5):1683-1691. doi: 10.1208/s12249-016-0612-1. Epub 2016 Sep 30.
Nanosizing is frequently used as formulation approach to increase the bioavailability of poorly water-soluble drugs. However, standard size reduction processes can be relatively time-consuming. It was found that the modification of the physical properties of a starting material by means of spray-drying can be used to improve the effectiveness of a subsequently performed high pressure homogenization. Such a process belongs to the combinative particle size reduction methods and is also referred to as H 42 process. Based on previous studies, it was hypothesized that the improved efficiency was a result of reduced crystallinity of the modified drug. The present study was conducted in order to asses this hypothesis in a systematical manner by applying design of experiment (DoE) principles. Resveratrol was selected as model compound for this study. It was processed by both standard high pressure homogenization and by a combinative particle size reduction process (the H42 process). An optimized resveratrol/surfactant ratio for the spray-dried intermediate was identified by using the response-surface methodology. The optimization led to a nanosuspension with a mean particle size of 192 nm, which is much smaller than the mean particle size of 569 nm when standard high pressure homogenization was used. Both predominately crystalline and predominately amorphous solids resulted from the spray-drying process. In contrast to the initial hypothesis, the smallest particle sizes were achieved by processing predominately crystalline intermediate with high pressure homogenization.
纳米化通常被用作一种制剂方法来提高难溶性药物的生物利用度。然而，标准的尺寸减小过程可能相对耗时。研究发现，通过喷雾干燥改变起始物料的物理性质可用于提高随后进行的高压均质化的效果。这样的过程属于组合式粒度减小方法，也被称为H 42过程。基于先前的研究，推测效率提高是改性药物结晶度降低的结果。本研究旨在通过应用实验设计（DoE）原则以系统的方式评估这一假设。白藜芦醇被选为该研究的模型化合物。它通过标准高压均质化和组合式粒度减小过程（H42过程）进行处理。通过使用响应面方法确定了喷雾干燥中间体的白藜芦醇/表面活性剂的最佳比例。优化后得到了平均粒径为192 nm的纳米混悬液，这比使用标准高压均质化时的平均粒径569 nm小得多。喷雾干燥过程产生了主要为结晶态和主要为无定形态的固体。与最初的假设相反，通过对主要为结晶态的中间体进行高压均质化处理得到了最小的粒径。
