与压缩口服固体剂型(OSD)有关的质量问题,比如药片,出现在设计过程中,发展,和生产阶段,尽管已经建立了流程和强大的生产工具。主要的质量问题之一是速释OSD产品的崩解特性和药物释放曲线,这取决于它们在晶粒水平上的微观纹理和微观粘弹性。这些特性受配方组成的影响,特别是片剂基质中的崩解剂水平和基质的孔隙率。在这项研究中,一本小说,快速,提出了无损超声表征技术来关联传播弹性波速度的灵敏度,物理/机械性能,和OSD材料在制剂中具有崩解剂水平(%w/w)和压片期间施加的压缩力的分散曲线。所提出的表征框架涉及通过OSD传输压力(纵向)和剪切(横向)波以计算声速,这反过来又提供了关于表观杨氏模量和剪切模量的信息。此外,通过色散分析获得传播波的衰减曲线。为了研究崩解剂和压缩力对OSD中超声波传播的影响,我们纳入了常用崩解剂的七个水平。在每个配方中,OSD在五种压实力下压实。波速的灵敏度,物理/机械性能,在每种崩解剂和压缩力水平下观察到衰减曲线。超声波技术的利用可能为快速,非破坏性的,非侵入性,以及连续制造(CM)和实时发布测试(RTRT)所需的具有成本效益的测试方法,并讨论了其在制药中的实际应用。
Quality issues related to compressed oral solid dosage (OSD) forms, such as tablets, arise during the design, development, and production stages, despite established processes and robust production tools. One of the primary quality concerns is the disintegration properties and drug release profile of immediate-release OSD products, which depend on their micro-texture and micro-viscoelastic properties at the grain level. These properties are influenced by the composition of the formulation, particularly the
disintegrant level in the tablet matrix and the porosity of the matrix. In this study, a novel, rapid, non-destructive ultrasonic characterization technique was proposed to correlate the sensitivity of propagating elastic wave speeds, physical/mechanical properties, and the dispersion profile of the OSD material with the
disintegrant level (% w/w) in the formulation and the compression force applied during tableting. The proposed characterization framework involves transmitting pressure (longitudinal) and shear (transverse) waves through the OSDs to calculate the speed of sound, which in turn provides information on the apparent Young\'s and shear moduli. In addition, the attenuation profile of the propagating wave is obtained through dispersion analysis. To investigate the impact of disintegrants and compression force on ultrasonic wave propagation in OSDs, we incorporated seven levels of a frequently used
disintegrant. In each formulation, OSDs are compacted in five compaction forces. The sensitivity of wave speeds, physical/mechanical properties, and attenuation profile was observed with each
disintegrant and compression force level. The utilization of ultrasonic techniques may present a viable solution for rapid, non-destructive, non-invasive, and cost-effective testing methods required in continuous manufacturing (CM) and real-time release testing (RTRT), and its practical utility in pharmaceutical manufacturing is also discussed.