STTR Phase I: Ultrasonic Measurement Instrument for Pharmaceutical Tablet Design, Development, and Continuous Manufacturing

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响/商业潜力是改善药品生产的质量控制。压缩片剂是世界上最流行的药物剂型。尽管其完善的生产工艺，但平板电脑的质量问题经常出现。其设计和制造中的问题有可能产生重大的医疗和财务影响，因为质量失败可能导致对患者的伤害、产品召回和药品短缺。提议的超声波测量仪器（UMI）单元将大大缩短片剂设计/开发周期，并在发布前检测/识别生产和质量问题。它在现代连续生产线上的应用将最大限度地降低不良片剂生产/处置和昂贵的产品召回/处置的风险。统一计量单位将产生两种不同的解决方案：(i)连续生产生产线的实时预防性质量监测装置和（ii）用于描述片剂物理特性的独立实验室设备。我们基于umi的产品的目标用户包括制药商；设备供应商;仿制药生产商；企业和大学的研发团队和药物开发团队；还有复方药房。这个小型企业技术转移（STTR）第一期项目及其超声波方法在药品生产质量评估和监测技术竞争中具有几个关键优势。与其他检测技术不同，超声波直接与质量密度、材料弹性/粘弹性、缺陷/裂纹和介质的不均匀性相互作用，压电换能器是瞬态应变传感最敏感的设备。在MHz频率下工作，超声波技术可以在相关波长上对片剂和缺陷尺寸（微米到毫米尺度）进行快速（微秒尺度）测量。需要解决的挑战包括：(i)具有微结构的粘弹性片剂材料的现有波传播模型不足以用超声波准确地表征/评估材料；（ii）片剂需要精确的处理和定位设备，因为对于机器学习和数据分析/挖掘，需要可重复获取和处理大型数据集。该项目的主要成果是一个概念验证测试/测量单元（UMI），具有精确的平板处理子系统及其伴随的用于形成大型数据集的数学算法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to improve quality control in pharmaceutical manufacturing. The compressed tablet is the most popular pharmaceutical dosage form in use worldwide. Despite its well-established manufacturing processes, issues with tablet quality are frequent. Issues in its design and manufacturing have the potential to make significant medical and financial impacts as failures in quality may result in harm to patients, product recalls, and medicine shortages. The proposed Ultrasonic Measurement Instrument (UMI) unit will substantially shorten drug tablet design/development cycles and detect/identify manufacturing and quality problems before release. Its utilization in modern continuous manufacturing lines will minimize the risk of defective tablet production/disposition and costly product recalls/disposals. The UMI unit will lead to two distinct solutions: (i) a real-time preventive quality monitoring device for continuous manufacturing production line and (ii) a stand-alone laboratory equipment for characterizing tablet physical properties. The target users for our UMI-based products include pharmaceutical manufacturers; equipment providers; generic drug manufacturers; R&D groups and drug development teams in corporations and universities; and compounding pharmacies.This Small Business Technology Transfer (STTR) Phase I project and its ultrasonic approach have several critical advantages over the competing quality assessment and monitoring technologies for pharmaceutical manufacturing. Unlike other detection techniques, ultrasound directly interacts with the mass density, material elasticity/viscoelasticity, defects/cracks, and inhomogeneities of a medium and piezoelectric transducers are the most sensitive devices for transient strain sensing. Operating in MHz frequency, ultrasonic techniques make rapid (micro-seconds scale) measurements at relevant wavelengths for tablet and defect sizes (micrometer to millimeter scales). Challenges to be addressed include: (i) existing wave propagation models for viscoelastic tablet materials with microstructures are inadequate for accurate materials characterization/valuation with ultrasound, and (ii) a precise handling and positioning apparatus for tablets is needed, as for machine learning and data analytics/mining, the repeatable acquisition and processing of large data sets are required. The main outcome of the project is a proof-of-concept testing/measurement unit (UMI) with a precise tablet handling sub-system and its accompanying mathematical algorithms for the formation of large data sets.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.