PFI-RP: Commercializing innovations in design and manufacture of fine pharmaceutical powders for cheaper and better medicines

PFI-RP：将精细药粉的设计和制造创新商业化，以提供更便宜、更好的药品

• 批准号: 1919037
• 负责人: Rajesh Dave
• 金额: $ 55万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1919037&HistoricalAwards=false
• 关键词: PFI; RP; Commercializing; innovations; design

The broader impact/commercial potential of this Partnerships for Innovation - Research Partnerships (PFI-RP) project is in making technologies available to improve manufacturing of powder-based products in a variety of industries, including pharmaceutical. These industries are increasingly dealing with fine powders, desirable because they improve product performance. Unfortunately, fine powder-based products pose significant difficulties in manufacturing and cause product failures due to their intrinsic poor processability and tendency to form large lumps. The innovation comes through scientific understanding of why fine powders behave poorly, and determining how their surfaces could be modified via novel mechanical processes to drastically and predictively improve their behavior. Significant commercial impact is expected from shorter drug product development times and reduced pharmaceutical product failures, as well as from increased profits in manufacturing tablet-based drug products. Societal impact comes from making available higher quality medicines to patients at lower costs. It will have a positive impact on the professional development of students participating in the project, through training in cutting-edge research, innovation and entrepreneurship. In addition, the proposed science teacher training will impact K-12 participants from school districts with large underrepresented minority populations. The proposed project will fundamentally advance understanding of how fine powders behave and why they lead to significant manufacturing challenges. The Intellectual merit of the project stems from physics-based models explaining why fine smooth particles, as well as rough particles (less than third the diameter of human hair), flow and pack poorly. However, when they are nano-rough, i.e., having surface asperities 500 times smaller than the diameter of human hair, they flow and pack significantly better. The understanding and development of mechanical processes to economically create nano-rough surfaces offer commercialization opportunities for the pharmaceutical industry. These include benefits from novel fine engineered drug powders flowing as well as those 5-10 times their size, and development of fine excipients that outperform their larger commercial counterparts in flow, packing, and tablet forming capability. The proposed novel advanced models should also help design the powders and their blends that form the building blocks of pharmaceutical products, such as tablets and capsules. If successful, these models will eliminate excessive time and material-consuming experimentation that increases manufacturing costs. Associated simulations will enable computer-assisted design of tablets, leading to better and cheaper drug products. Additional intellectual merit of the project is through the participation of students with industry partners and mentors while engaging in research targeted for commercialization.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.

这一创新-研究伙伴关系（PFI-RP）项目的更广泛影响/商业潜力在于提供技术，以改善包括制药在内的各种行业的粉末产品制造。这些行业越来越多地处理精细粉末，因为它们改善了产品性能。不幸的是，基于细粉末的产品在制造中造成了显著的困难，并且由于其固有的差的可加工性和形成大块的倾向而导致产品失效。这项创新来自于对精细粉末性能差的原因的科学理解，并确定如何通过新的机械工艺对其表面进行改性，以大幅和预测性地改善其性能。 预计将产生重大的商业影响，因为药物产品开发时间缩短，药物产品故障减少，以及生产片剂药物产品的利润增加。社会影响来自以较低的成本向患者提供更高质量的药品。它将通过尖端研究、创新和创业方面的培训，对参与该项目的学生的专业发展产生积极影响。此外，拟议的科学教师培训将影响来自少数民族人口比例偏低的学区的K-12参与者。拟议的项目将从根本上推进对精细粉末行为的理解，以及为什么它们会导致重大的制造挑战。该项目的智力价值源于基于物理学的模型，解释了为什么精细光滑颗粒以及粗糙颗粒（直径小于人类头发的三分之一）流动和包装不良。然而，当它们是纳米粗糙的时，即，具有比人的头发直径小500倍的表面粗糙度，它们的流动和堆积明显更好。理解和开发机械工艺以经济地制造纳米粗糙表面为制药行业提供了商业化机会。这些优点包括新型精细工程药物粉末的流动性以及其尺寸的5-10倍，以及开发在流动性，包装和片剂形成能力方面优于其较大商业对应物的精细赋形剂。所提出的新型先进模型还应有助于设计粉末及其混合物，这些粉末及其混合物构成了片剂和胶囊等药品的基础。如果成功，这些模型将消除过多的时间和材料消耗实验，增加制造成本。相关的模拟将使计算机辅助设计的片剂，导致更好和更便宜的药品。 该项目的其他智力价值是通过学生与行业合作伙伴和导师的参与，同时从事针对商业化的研究。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Air entrapment during tablet compression – Diagnosis, impact on tableting performance, and mitigation strategies

片剂压缩过程中的空气滞留 — 诊断、对压片性能的影响以及缓解策略

• DOI: 10.1016/j.ijpharm.2022.121514
• 发表时间: 2022
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Vreeman, Gerrit;Sun, Changquan Calvin
• 通讯作者: Sun, Changquan Calvin

Assessing predictability of packing porosity and bulk density enhancements after dry coating of pharmaceutical powders

• DOI: 10.1016/j.powtec.2020.09.037
• 发表时间: 2021-01
• 期刊: Powder Technology
• 影响因子: 5.2
• 作者: Kuriakose T. Kunnath;Liang Chen;K. Zheng;R. Davé

Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size

通过干包衣增强低载药量精细 API 混合物的混合均匀性和流动性：混合时间和赋形剂尺寸的影响

• DOI: 10.1016/j.ijpharm.2023.122722
• 发表时间: 2023
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Kim, Sangah S.;Castillo, Chelsea;Cheikhali, Mirna;Darweesh, Hadeel;Kossor, Christopher;Davé, Rajesh N.
• 通讯作者: Davé, Rajesh N.

Exploring tablet design options for tailoring drug release and dose via fused deposition modeling (FDM) 3D printing

• DOI: 10.1016/j.ijpharm.2020.119987
• 发表时间: 2020-12-15
• 期刊: INTERNATIONAL JOURNAL OF PHARMACEUTICS
• 影响因子: 5.8
• 作者: Buyukgoz, Guluzar Gorkem;Soffer, David;Dave, Rajesh N.
• 通讯作者: Dave, Rajesh N.

Impact of Silica Dry Coprocessing with API and Blend Mixing Time on Blend Flowability and Drug Content Uniformity

二氧化硅与 API 干法协同处理和共混物混合时间对共混物流动性和药物含量均匀性的影响

• DOI: 10.1016/j.xphs.2023.05.016
• 发表时间: 2023
• 期刊: Journal of Pharmaceutical Sciences
• 影响因子: 3.8
• 作者: Kim, Sangah S.;Seetahal, Ameera;Amores, Nicholas;Kossor, Christopher;Davé, Rajesh N.
• 通讯作者: Davé, Rajesh N.