RISE Research Intitutes of Sweden, Division of Bioscience and Materials, Box 5607, SE-114 86Stockholm, Sweden; KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Drottning Kristinas väg 51, SE-100 44, Stockholm, Sweden.
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Int J Pharm. 2018 Feb 15;537(1-2):140-147. doi: 10.1016/j.ijpharm.2017.12.021. Epub 2017 Dec 17.
Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. However, such operations may induce undesired material properties modifications when conditioning particle size through milling, for example. Modification of both surface and bulk material structure will change the material properties, thus affecting the processability of the powder. Hence it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore a surface evaluation of the α-lactose monohydrate after short and prolonged milling times has been performed. Unprocessed α-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between unprocessed α-lactose, 1 h and 20 h milled lactose and spray dried lactose were detected from SEM and AFM images. Additionally, AFM was used to simultaneously characterize particle surface amorphicity by measuring energy dissipation. Extensive surface amorphicity was detected after 1 h of milling while prolonged milling times showed only a moderate particle surface amorphisation. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1 h milled lactose and a fully amorphous thermal profile for the 20 h milled lactose. The temperature profiles however, were shifted somewhat in the comparison to the amorphous reference, particularly after extended milling, suggesting a different amorphous state compared to the spray-dried material. Water loss during milling was measured with TGA, showing lower water content for the lactose amorphized through milling compared to spray dried amorphous lactose. The combined results suggest a surface-bulk propagation of the amorphicity during milling in combination with a different amorphous structural conformation to that of the amorphous spray dried lactose. The hardened surface may be due to either surface crystallization of lactose or to formation of a low-water glass transition.
药物粉末的预处理是一种常见的工序，用于改善材料的制造性能。然而，例如通过研磨来调节颗粒尺寸时，这种操作可能会导致不希望的材料性质的改变。表面和体材料结构的改性都会改变材料的性质，从而影响粉末的加工性能。因此，控制研磨过程中发生的材料转变是至关重要的。表面性质的形貌和力学变化可以作为进一步材料转变的初步指示。因此，对经过短时间和长时间研磨的 α-乳糖一水合物进行了表面评估。未处理的 α-乳糖一水合物和喷雾干燥乳糖被评估为与研磨样品平行的参考示例，以评估结晶和无定形乳糖结构。从 SEM 和 AFM 图像中检测到未处理的 α-乳糖、1 h 和 20 h 研磨的乳糖和喷雾干燥乳糖之间的形貌差异。此外，AFM 用于通过测量能量耗散来同时表征颗粒表面非晶度。研磨 1 h 后检测到广泛的表面非晶度，而延长研磨时间仅显示出适度的颗粒表面非晶化。使用 DSC 进行的体材料特性分析表明，1 h 研磨的乳糖部分非晶化，而 20 h 研磨的乳糖呈现完全无定形的热谱。然而，与无定形参考相比，温度曲线有些偏移，特别是在延长研磨后，这表明与喷雾干燥材料相比，存在不同的无定形状态。TGA 测量了研磨过程中的水分损失，显示出通过研磨非晶化的乳糖的含水量低于喷雾干燥的无定形乳糖。综合结果表明，在研磨过程中，非晶度从表面到体的传播与喷雾干燥的无定形乳糖的不同无定形结构构象相结合。硬化的表面可能是由于乳糖的表面结晶或形成低水分玻璃化转变。
