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.

该小型企业技术转移（STTR）I期项目的更广泛的影响/商业潜力是改善制药制造中的质量控制。压缩平板电脑是全球使用中最受欢迎的药品剂型。尽管其制造过程良好，但具有平板电脑质量的问题频繁。由于质量失败可能会对患者，产品召回和医学短缺，其设计和制造业的问题有可能对医疗和财务产生重大影响。拟议的超声测量仪器（UMI）单元将大大缩短药品片剂的设计/开发周期，并在释放前检测/识别制造和质量问题。它在现代连续制造线路中的利用将最大程度地减少平板电脑生产/处置有缺陷的风险和昂贵的产品召回/处置。 UMI单元将导致两种不同的解决方案：（i）用于连续制造生产线的实时预防质量监控设备，以及（ii）一种用于表征平板电脑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；设备提供商；通用药物制造商；公司和大学的研发小组和药物开发团队；这一小型企业技术转移（STTR）I阶段项目及其超声波方法在竞争质量评估和监测技术制造技术方面具有多个关键优势。与其他检测技术不同，超声直接与质量密度，材料弹性/粘弹性，缺陷/裂纹以及培养基和压电传感器的不均匀性相互作用是瞬时应变感应的最灵敏的设备。超声波技术以MHz频率运行，在相关波长的平板电脑和缺陷尺寸（微米至毫米尺度）上进行快速（微秒尺度）测量。要解决的挑战包括：（i）带有微观结构的粘弹性平板电脑材料的现有波浪传播模型不足以进行超声进行超声处理的准确材料表征/估值，（ii）需要用于平板电脑的精确处理和定位设备，如机器学习和数据分析和挖掘，可重复的批准，需要大型数据集。 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.

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
• 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

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
• 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-Chao;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
• 期刊: AAPS PharmSciTech
• 影响因子: 3.3
• 作者: Sultan, Tipu;Paul, Shubhajit;Rozin, Enamul Hasan;Tseng, Yin-Chao;Bazzocchi, Michael C.;Cetinkaya, Cetin
• 通讯作者: Cetinkaya, Cetin