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

这个小型企业技术转让(STTR)第一阶段项目的更广泛的影响/商业潜力是改善制药制造的质量控制。压片是全世界使用的最受欢迎的药物剂型。尽管其成熟的制造工艺，但平板电脑的质量问题仍然屡见不鲜。它的设计和制造中的问题可能会造成重大的医疗和财务影响，因为质量问题可能会导致对患者的伤害、产品召回和药品短缺。拟议的超声测量仪器(UMI)单元将大大缩短药物片剂的设计/开发周期，并在发布之前检测/识别制造和质量问题。它在现代连续生产线中的应用将最大限度地降低片剂生产/处置缺陷和昂贵的产品召回/处置的风险。UMI部门将产生两种不同的解决方案：(I)用于连续生产生产线的实时预防性质量监控设备；(Ii)用于表征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药品制造商；设备供应商；仿制药制造商；企业和大学的研发团队和药物开发团队；以及复合制药。这一小型企业技术转移(STTR)第一阶段项目及其超声波方法与制药生产的竞争质量评估和监测技术相比具有几个关键优势。与其他检测技术不同，超声波直接与介质的质量密度、材料弹性/粘弹性、缺陷/裂纹和不均匀性相互作用，而压电换能器是最敏感的瞬时应变传感设备。超声波技术工作在MHz频率，可在相关波长(微秒级)对药片和缺陷大小(微米到毫米级)进行快速测量。需要解决的挑战包括：(I)现有的具有微结构的粘弹性片剂材料的波传播模型不足以通过超声波对材料进行准确的表征/评估，以及(Ii)需要片剂的精确处理和定位设备，对于机器学习和数据分析/挖掘，需要对大数据集进行可重复的采集和处理。该项目的主要成果是概念验证测试/测量单元(UMI)，具有精确的平板处理子系统及其形成大型数据集的随附数学算法。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.