Jagiellonian University, Medical College, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, 9 Medyczna Street, 30-688 Cracow, Poland; University of Lille, CNRS, INRAE, Centrale Lille, UMR 8207, UMET - Unité Matériaux et Transformations, F-59000 Lille, France.
University of Lille, CNRS, INRAE, Centrale Lille, UMR 8207, UMET - Unité Matériaux et Transformations, F-59000 Lille, France.
Eur J Pharm Biopharm. 2023 Jul;188:137-146. doi: 10.1016/j.ejpb.2023.05.014. Epub 2023 May 15.
In this study, high energy ball milling and nano spray drying were used to prepare amorphous solid dispersions of bosentan in copovidone for the first time. In particular, the impact of this polymer on the bosentan amorphization kinetics was investigated. Copovidone was shown to facilitate the amorphization of bosentan upon ball milling. As a result, bosentan was dispersed in copovidone at the molecular level, forming amorphous solid dispersions, regardless of the ratio of the compounds. The similarity between the values of the adjustment parameter that describes the goodness of fit of the Gordon-Taylor equation to the experimental data (K = 1.16) and that theoretically calculated for an ideal mixture (K = 1.13) supported these findings. The kind of coprocessing method determined the powder microstructure and the release rate. The opportunity to prepare submicrometer-sized spherical particles using nano spray drying was an important advantage of this technology. Both coprocessing methods allowed the formation of long-lasting supersaturated bosentan solutions in the gastric environment with maximum concentrations reached ranging from four (11.20 μg/mL) to more than ten times higher (31.17 μg/mL) than those recorded when the drug was vitrified alone (2.76 μg/mL). Moreover, this supersaturation lasted for a period of time at least twice as long as that of the amorphous bosentan processed without copovidone (15 min vs. 30-60 min). Finally, these binary amorphous solid dispersions were XRD-amorphous for a year of storage under ambient conditions.
在这项研究中，首次使用高能球磨和纳米喷雾干燥法制备了泊沙康唑与共聚维酮的无定形固体分散体。特别地，研究了该聚合物对泊沙康唑非晶化动力学的影响。研究表明，共聚维酮有助于泊沙康唑在球磨过程中实现非晶化。结果，泊沙康唑以分子水平分散在共聚维酮中，形成无定形固体分散体，而与化合物的比例无关。描述 Gordon-Taylor 方程拟合实验数据的调整参数值（K=1.16）与理论上计算的理想混合物的参数值（K=1.13）非常接近，这支持了上述发现。共处理方法的种类决定了粉末的微观结构和释放速率。使用纳米喷雾干燥制备亚微米级球形颗粒的机会是该技术的一个重要优势。这两种共处理方法都允许在胃环境中形成持久的过饱和泊沙康唑溶液，最大浓度范围从四倍（11.20μg/mL）到十倍以上（31.17μg/mL），高于单独将药物玻璃化时记录到的浓度（2.76μg/mL）。此外，这种过饱和度的持续时间至少是无共聚维酮处理的非晶泊沙康唑的两倍（15 分钟对 30-60 分钟）。最后，这些二元无定形固体分散体在环境条件下储存一年仍保持 X 射线无定形态。
