a Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin , Austin , TX , USA.
b DisperSol Technologies, LLC , Georgetown , TX , USA.
Drug Dev Ind Pharm. 2019 May;45(5):724-735. doi: 10.1080/03639045.2019.1569037. Epub 2019 Jan 25.
KinetiSol is a high-shear, fusion-based technology capable of producing stable amorphous solid dispersions (ASDs) without the assistance of solvent. KinetiSol has proven successful with multiple challenging BCS class II and IV drugs, where drug properties like thermal instability or lack of appreciable solubility in volatile solvents make hot melt extrusion or spray drying unfeasible. However, there is a necessity to characterize the ASDs like those made by the KinetiSol process, in order to better understand whether KinetiSol is capable of homogeneously dispersing drug throughout a carrier in a short (<40 s) processing time. Our study utilized the high melting point, BCS class II drug, meloxicam, in order to evaluate the degree of homogeneity of 1, 5, and 10% w/w KinetiSol-processed samples. Powder blend homogeneity and content uniformity were evaluated, and all samples demonstrated a meloxicam concentration % relative standard deviation of ≤2.0%. SEM/EDS was utilized to map elemental distribution of the processed samples, which confirmed KinetiSol-processed materials were homogeneous at a 25 µm area. Utilizing Raman spectroscopy, we were able to verify the amorphous content of the processed samples. Finally, we utilized ssNMR H spin-lattice relaxation measurement to evaluate the molecular miscibility of meloxicam with the polymer at 1% w/w drug load, for the first time, and determined the processed sample was highly miscible at ∼200 nm scale. In conclusion, we determined the KinetiSol process is capable of producing ASDs that are homogeneously and molecularly well-dispersed drug-in-polymer at drug concentrations as low as 1% w/w.
KinetiSol 是一种高剪切融合技术，能够在不使用溶剂的情况下生产稳定的无定形固体分散体（ASD）。KinetiSol 已成功用于多种具有挑战性的 BCS 类 II 和 IV 药物，这些药物的特性如热不稳定性或在挥发性溶剂中缺乏可观的溶解度使得热熔挤出或喷雾干燥变得不可行。然而，有必要对 KinetiSol 工艺生产的 ASD 进行特性描述，以便更好地了解 KinetiSol 是否能够在短（<40 秒）的加工时间内将药物均匀地分散在载体中。我们的研究利用高熔点、BCS 类 II 药物美洛昔康来评估 1%、5%和 10%w/w KinetiSol 处理样品的均匀度。评估了粉末混合物的均匀性和含量均匀性，所有样品均显示美洛昔康浓度的相对标准偏差≤2.0%。SEM/EDS 用于绘制加工样品的元素分布图，证实 KinetiSol 加工材料在 25μm 面积上是均匀的。利用拉曼光谱，我们能够验证加工样品的无定形含量。最后，我们首次利用 ssNMR H 自旋晶格弛豫测量来评估 1%w/w 药物负载下美洛昔康与聚合物的分子混溶性，并确定加工样品在约 200nm 尺度上具有高度混溶性。总之，我们确定 KinetiSol 工艺能够生产 ASD，其药物在聚合物中的均匀性和分子分散性高达 1%w/w。
