Department of Mechanical and Aeronautical Engineering, Photo-Acoustics Research Laboratory, Center for Advanced Materials Processing, Clarkson University, Potsdam, NY 13699-5725, USA.
Int J Pharm. 2013 Sep 15;454(1):333-43. doi: 10.1016/j.ijpharm.2013.06.045. Epub 2013 Jun 29.
The mechanical properties of a solid dosage, defined by its granular micro-structure and geometry, play a key role in its dissolution profile and performance. An ultrasonic method for extracting the viscoelastic material properties and granular structure of drug tablet compacts is introduced and its utility is demonstrated for tablet compacts made of microcrystalline cellulose (MCC), lactose monohydrate, and sodium starch glycolate as well as magnesium stearate as lubricant. The approach is based on the effect of viscoelasticity and internal micro-structures on the frequency-dependent attenuation of an ultrasonic wave propagating in a granular medium. The models for viscoelastic (a two-parameter Zener model) and scattering attenuation (Rayleigh model) mechanisms are employed. The material parameters including viscoelastic and scattering parameters (average Young's modulus, stress and strain relaxation time constants, and the Rayleigh scattering material parameter) and grain size distribution with a known distribution profile are extracted by an optimization algorithm based on the least square method. The results also indicate good agreement between experimentally and computationally determined phase and group velocities in compacted samples. It is found that the effects of both attenuation mechanisms are present and the extracted grain size distribution parameters are in good agreement with the optically determined values.
固体剂型的机械性能由其颗粒微观结构和几何形状决定，在其溶解特性和性能中起着关键作用。本文介绍了一种用于提取药物片剂压缩物的粘弹性材料特性和颗粒结构的超声方法，并展示了其在由微晶纤维素（MCC）、乳糖一水合物、交联羧甲基纤维素钠以及硬脂酸镁作为润滑剂的片剂压缩物中的应用。该方法基于粘弹性和内部微观结构对在颗粒介质中传播的超声波的频率相关衰减的影响。采用粘弹性（双参数 Zener 模型）和散射衰减（瑞利模型）机制的模型。通过基于最小二乘法的优化算法提取材料参数，包括粘弹性和散射参数（平均杨氏模量、应力和应变松弛时间常数，以及瑞利散射材料参数）以及具有已知分布轮廓的颗粒尺寸分布。结果还表明，在压实样品中实验和计算确定的相速度和群速度之间具有良好的一致性。结果表明，两种衰减机制都存在，并且提取的颗粒尺寸分布参数与光学确定的值吻合良好。
