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Abstract：
Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal structure. The aim of this work is to study in situ dynamic, dispersion, chemical, biological and surface properties of lacosamide powder after a complete cycle of mechanical loading by laser scattering, electron microscopy, FR-IR and biopharmaceutical approaches. The SLS method demonstrated the spontaneous tendency toward surface-energy reduction due to aggregation during micronisation. DLS analysis showed conformational changes of colloidal particles as supramolecular complexes depending on the loading time on the solid. SEM analysis demonstrated the conglomeration of needle-like lacosamide particles after 60 min of milling time and the transition to a glassy state with isotropy of properties by the end of the tribochemistry cycle. The following dynamic properties of lacosamide were established: elastic and plastic deformation boundaries, region of inhomogeneous deformation and fracture point. The ratio of dissolution-rate constants in water of samples before and after a full cycle of loading was 2.4. The lacosamide sample, which underwent a full cycle of mechanical loading, showed improved kinetics of API release via analysis of dissolution profiles in 0.1 M HCl medium. The observed activation-energy values of the cell-death biosensor process in aqueous solutions of the lacosamide samples before and after the complete tribochemical cycle were 207 kJmol-1 and 145 kJmol-1, respectively. The equilibrium time of dissolution and activation of cell-biosensor death corresponding to 20 min of mechanical loading on a solid was determined. The current study may have important practical significance for the transformation and management of the properties of drug substances in solid form and in solutions and for increasing the strength of drug matrices by pre-strain hardening via structural rearrangements during mechanical loading.
摘要：
固体的许多物理和化学性质，比如力量,可塑性,分散性,溶解度和溶解取决于晶体结构中的缺陷。这项工作的目的是研究原位动力学，色散，化学,通过激光散射进行完整的机械加载循环后，拉科酰胺粉末的生物学和表面特性，电子显微镜，FR-IR和生物制药方法。SLS方法证明了由于微粉化过程中的聚集而导致的表面能降低的自发趋势。DLS分析显示胶体颗粒作为超分子复合物的构象变化取决于在固体上的加载时间。SEM分析表明，在60分钟的研磨时间后，针状拉科酰胺颗粒聚集，并在摩擦化学循环结束时转变为具有各向同性性质的玻璃态。建立了拉科沙胺的以下动态特性：弹性和塑性变形边界，不均匀变形区域和断裂点。在整个加载周期之前和之后，样品在水中的溶解速率常数之比为2.4。拉科沙胺样本,它经历了一个完整的机械加载周期，通过分析在0.1MHCl介质中的溶解曲线显示出改善的API释放动力学。在完整的摩擦化学循环之前和之后，在lacosamide样品的水溶液中观察到的细胞死亡生物传感器过程的活化能值分别为207kJmol-1和145kJmol-1。确定了溶解和激活细胞-生物传感器死亡的平衡时间，对应于固体上20分钟的机械负载。当前的研究对于固体形式和溶液中药物物质的性质的转变和管理以及通过在机械加载期间通过结构重排进行预应变硬化来增加药物基质的强度可能具有重要的现实意义。
