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

STTR 第一阶段：用于药物片剂设计、开发和连续制造的超声波测量仪器

• 批准号: 2051895
• 负责人: Cetin Cetinkaya
• 金额: $ 25.6万
• 依托单位: PHARMACOUSTICS TECHNOLOGIES LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2051895&HistoricalAwards=false
• 关键词: STTR; Phase; Ultrasonic; Measurement; Instrument

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.

该小型企业技术转让 (STTR) 第一阶段项目的更广泛影响/商业潜力是改善药品制造的质量控制。压缩片剂是全球最流行的药物剂型。尽管其制造工艺完善，但片剂质量问题仍然频繁发生。其设计和制造中的问题可能会产生重大的医疗和财务影响，因为质量缺陷可能会导致患者受伤、产品召回和药品短缺。拟议的超声波测量仪器（UMI）装置将大大缩短药片设计/开发周期，并在发布前检测/识别制造和质量问题。它在现代连续生产线中的使用将最大限度地减少有缺陷的片剂生产/处置和昂贵的产品召回/处置的风险。 UMI 单元将带来两种不同的解决方案：(i) 用于连续生产线的实时预防性质量监控设备和 (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制药商；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；这个小型企业技术转让 (STTR) 第一阶段项目及其超声波方法与药品制造的竞争质量评估和监控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，压电换能器是瞬态应变传感最敏感的设备。超声波技术以 MHz 频率运行，可在相关波长下快速（微秒级）测量药片和缺陷尺寸（微米至毫米级）。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通过超声波进行精确的材料表征/评估，以及（ii）需要用于片剂的精确处理和定位设备，如机器学习和需要数据分析/挖掘、可重复采集和处理大型数据集。该项目的主要成果是概念验证测试/测量单元 (UMI)，具有精确的药片处理子系统及其随附的数学算法，用于形成大型数据集。该奖项反映了 NSF 的法定使命，并已通过使用基金会的智力优点和更广泛的影响审查标准进行评估，认为值得支持。

项目成果

Effect of shape on the physical properties of pharmaceutical tablets

形状对片剂物理性质的影响

• DOI: 10.1016/j.ijpharm.2022.121993
• 发表时间: 2022-08
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Sultan, Tipu;Xu, Xiaochi;Hasan Rozin, Enamul;Sorjonen, Joona;Ketolainen, Jarkko;Wikström, Håkan;Martin de Juan, Luis;Tajarobi, Pirjo;Cetinkaya, Cetin
• 通讯作者: Cetinkaya, Cetin

Micro-viscoelastic Characterization of Compressed Oral Solid Dosage Forms with Ultrasonic Wave Dispersion Analysis

用超声波色散分析表征压缩口服固体剂型的微观粘弹性

• DOI: 10.1208/s12249-022-02483-7
• 发表时间: 2023-01
• 期刊: AAPS PharmSciTech
• 影响因子: 3.3
• 作者: Sultan, Tipu;Paul, Shubhajit;Rozin, Enamul Hasan;Tseng, Yin;Bazzocchi, Michael C.;Cetinkaya, Cetin
• 通讯作者: Cetinkaya, Cetin

Ultrasonic characterization of complete anisotropic elasticity coefficients of compressed oral solid dosage forms

压缩口服固体剂型完全各向异性弹性系数的超声表征

• DOI: 10.1016/j.ijpharm.2022.121922
• 发表时间: 2022-07
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Sultan, Tipu;Paul, Shubhajit;Hasan Rozin, Enamul;Canino, Christian;Tseng, Yin;Cetinkaya, Cetin
• 通讯作者: Cetinkaya, Cetin