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.

该创新伙伴关系 - 研究伙伴关系 (PFI-RP) 项目更广泛的影响/商业潜力在于提供技术来改善包括制药在内的各种行业的粉末产品的制造。这些行业越来越多地处理细粉末，这是理想的，因为它们可以提高产品性能。不幸的是，基于细粉末的产品在制造中造成了很大的困难，并且由于其固有的加工性差和形成大块的倾向而导致产品失败。这项创新源于对细粉末性能不佳原因的科学理解，并确定如何通过新颖的机械工艺对其表面进行改性，以显着且可预测地改善其性能。 药品开发时间的缩短、药品失败的减少以及片剂药品生产利润的增加预计将产生重大的商业影响。社会影响来自于以更低的成本向患者提供更高质量的药物。通过前沿研究、创新和创业方面的培训，将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大量少数族裔人口代表性不足的学区的 K-12 参与者。拟议的项目将从根本上增进对细粉末行为方式以及它们为何会带来重大制造挑战的理解。该项目的智力价值源于基于物理的模型，解释了为什么细小的光滑颗粒和粗糙颗粒（小于人类头发直径的三分之一）的流动和堆积性能较差。然而，当它们达到纳米粗糙度时，即表面粗糙度比人类头发直径小 500 倍时，它们的流动性和堆积性明显更好。对经济地制造纳米粗糙表面的机械工艺的理解和开发为制药行业提供了商业化机会。其中包括新型精细工程药物粉末的流动性以及其尺寸的 5-10 倍的优势，以及开发在流动性、包装和片剂成型能力方面优于大型商业同类药物的精细赋形剂。所提出的新型先进模型还应有助于设计粉末及其混合物，以构成片剂和胶囊等药品的基础材料。如果成功，这些模型将消除过多的时间和材料消耗实验，从而增加制造成本。相关模拟将使计算机辅助设计片剂成为可能，从而生产出更好、更便宜的药品。 该项目的额外智力价值是通过学生与行业合作伙伴和导师的参与，同时参与针对商业化的研究。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

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: 2023-03
• 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.

Impact of altered hydrophobicity and reduced agglomeration on dissolution of micronized poorly water-soluble drug powders after dry coating

改变疏水性和减少团聚对微粉化难水溶性药物粉末干包衣后溶出的影响

• DOI: 10.1016/j.ijpharm.2021.120853
• 发表时间: 2021-09
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Kim, Sangah;Bilgili, Ecevit;Davé, Rajesh N.
• 通讯作者: Davé, 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: 2023-05
• 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.

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: 2022-03
• 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

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

探索通过熔融沉积建模 (FDM) 3D 打印定制药物释放和剂量的片剂设计方案

• DOI: 10.1016/j.ijpharm.2020.119987
• 发表时间: 2020-12
• 期刊: International Journal of Pharmaceutics
• 影响因子: 5.8
• 作者: Gorkem Buyukgoz, Guluzar;Soffer, David;Defendre, Jackenson;Pizzano, Gia M.;Davé, Rajesh N.
• 通讯作者: Davé, Rajesh N.