Cross-Pharma Collaboration on the Development and Evaluation of a New Mid-Scale Preparative Supercritical Fluid Chromatography Instrument

Biba, Mirlinda; Wong, Mengling; Akin, Anne; Manning, Eric T.; Schaffter, Lisa M.; Miller, Larry; Zhang, Yingru; Farrell, William; DaSilva, Jimmy; Nogle, Lisa; Hritzko, Benjamin; Riley, Frank; DePianta, Robert P.; Barry, Kevin Joseph; Gao, Donghong A.; Seest, Eric P.; Goel, Meenakshi; Chung, Loanne; Paulson, James; Lee, Heewon; Moore, Donald R.; Shu-ping, Dong; Leister, William; Fukushima, Nobumitsu; Sasaki, Andy; Lee, Timothy J.; Iriki, Takayuki; Nishimura, Masayuki; Tomita, Masami; Owa, Michiaki; Shagawa, Tomohiro; Moran, Thomas J.; Bamba, Takeshi; Welch, Christopher J.

doi:10.1021/acs.oprd.0c00136

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Since a supercritical fluid can easily percolate into a sample, it is possible to obtain extracts from a sample more efficiently than with a liquid. 52) Moreover, because supercritical carbon dioxide becomes a gas under atmospheric pressure, there is almost no need to evaporate solvents from eluents. However, it is difficult to collect the whole eluents on a small scale with a high recovery rate.…”

Section: Microfluidic Technology For Sfcmentioning

confidence: 99%

Emerging Separation Techniques in Supercritical Fluid Chromatography

Yamamoto

Machida

Kotani

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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Supercritical fluid chromatography (SFC) has unique separative characteristics distinguished from those of HPLC and gas chromatography. At present, SFC is widely used and there are many applications in various biological, medical, and pharmaceutical fields. In this review, we focus on recently developed novel techniques related to SFC separation including: new column stationary phases, microfluidics, twodimensional separation, and gas-liquid separation. In addition, we discuss the application of SFC using a water-containing modifier to biological molecules such as amino acids, peptides, and small proteins that had been challenging analytes.

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Section: Microfluidic Technology For Sfcmentioning

confidence: 99%

Emerging Separation Techniques in Supercritical Fluid Chromatography

Yamamoto

Machida

Kotani

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…First, performing SFC purifications with a deuterated modifier would be considerably costly unless it is carried out on an analytical scale. Surprisingly, the availability of analytical/midscale SFC instrumentation with automated fraction collection was achieved only in the last 5–10 years, with a limited number of papers showcasing its potential . Second, investigations of the use of deuterated modifiers in SFC and its impact on chromatographic performance across a wide spectrum of analytes are nonexistent.…”

Section: Introductionmentioning

confidence: 99%

Deuterated Modifiers in Sub/Supercritical Fluid Chromatography for Streamlined NMR Structure Elucidation

et al. 2022

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Isolation and chemical characterization of target components in fast-paced pharmaceutical laboratories can often be challenging, especially when dealing with mixtures of closely related, possibly unstable species. Traditionally, this process involves intense labor and manual intervention including chromatographic method development and optimization, fraction collection, and drying processes prior to NMR analyses for unambiguous structure elucidation. To circumvent these challenges, a foundational framework for the proper utilization of supercritical carbon dioxide (scCO 2 ) and deuterated modifiers (CD 3 OD) in sub/supercritical fluid chromatography (SFC) is herein introduced. This facilitates a streamlined multicomponent isolation with minimized protic residues, further enabling immediate NMR analysis. In addition to bypassing tedious drying processes and minimizing analyte degradation, this approach (complementary to traditional reversed-phase liquid chromatography, RPLC) delivers highly efficient separations and automated fraction collection using readily available analytical/midscale SFC instrumentation. A series of diverse analytes across a wide spectrum of chemical properties (acid, basic, and neutral), combined with different stationary-phase columns in SFC are investigated using both a protic organic modifier (CH 3 OH) and its deuterated counterpart (CD 3 OD). The power of this framework is demonstrated with pharmaceutically relevant applications in the context of target characterization and analysis of complex multicomponent reaction mixtures from modern synthetic chemistry, demonstrating high isolation yields while reducing both the environmental footprint and manual intervention. This workflow enables unambiguous fast-paced structure elucidation on the analytical scale, providing results that are comparable to traditional, but time-consuming, RPLC purification approaches.

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“…For many ETC projects, future users are directly involved in product development, at times serving as high-level technical advisors and β-testers. Some of the successful ETC collaborations have been reported in the literature. , We report the achievements of one of the first ETC projects, which has resulted in a new population balance model (PBM)-based interactive, user-friendly crystallization software for pharmaceutical research and development. The key scope of such software tool is to perform process modeling and simulation of industrial crystallization processes by regressing model parameters from the experimental data.…”

Section: Introductionmentioning

confidence: 99%

Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)

Szilágyi

Eren

et al. 2021

Crystal Growth & Design

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Precompetitive collaborations on new enabling technologies for research and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes projects, often with third-party collaborators, to develop new tools and technologies of mutual interest. Here, we report the results of one of the first ETC projects: the development of a user-friendly population balance model (PBM)-based crystallization simulator software. This project required the development of PBM software with integrated experimental data handling, kinetic parameter regression, interactive process simulation, visualization, and optimization capabilities incorporated in a computationally efficient and robust software platform. Inputs from a team of experienced scientists at 10 ETC member companies helped define a set of software features that guided a team of crystallization modelers to develop software incorporating these features. Communication, continuous testing, and feedback between the ETC and the academic team facilitated the software development. The product of this project, a software tool called CrySiV, an acronym for Crystallization Simulation and Visualization, is reported herein. Currently, CrySiV can be used for cooling, antisolvent, and combined cooling and antisolvent crystallization processes, with primary and secondary nucleation, growth, dissolution, agglomeration, and breakage of crystals. This paper describes the features and the numerical methods of the software and presents two case studies demonstrating its use for parameter estimation. In the first case study, a simulated data set is used to demonstrate the capabilities of the software to find kinetic parameters and its goodness of fit to a known solution. In the second case study, the kinetics of an antisolvent crystallization of indomethacin from a ternary solvent system are estimated, providing a practical example of the tool.

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Cross-Pharma Collaboration on the Development and Evaluation of a New Mid-Scale Preparative Supercritical Fluid Chromatography Instrument

Cited by 7 publications

References 18 publications

Emerging Separation Techniques in Supercritical Fluid Chromatography

Emerging Separation Techniques in Supercritical Fluid Chromatography

Deuterated Modifiers in Sub/Supercritical Fluid Chromatography for Streamlined NMR Structure Elucidation

Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)

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