Organic Process Research & Development最新文献_第7页

Application of an Interdisciplinary Approach to Form Selection in Drug Development

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-01-25 DOI: 10.1021/acs.oprd.4c0032010.1021/acs.oprd.4c00320

Darren L. Reid*, Margaret M. Faul*, Vilmalí López-Mejías, Prashant Agarwal, Markus Bergauer, Laura E. Blue, Mary K. Chaves, John Chung, Melanie Cooke, Robert P. Farrell, James E. Huckle, Ron C. Kelly, Y.-H. Kiang, Weikun Li, Adrian Ortiz and Qiong Wu,

{"title":"Application of an Interdisciplinary Approach to Form Selection in Drug Development","authors":"Darren L. Reid*, Margaret M. Faul*, Vilmalí López-Mejías, Prashant Agarwal, Markus Bergauer, Laura E. Blue, Mary K. Chaves, John Chung, Melanie Cooke, Robert P. Farrell, James E. Huckle, Ron C. Kelly, Y.-H. Kiang, Weikun Li, Adrian Ortiz and Qiong Wu, ","doi":"10.1021/acs.oprd.4c0032010.1021/acs.oprd.4c00320","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00320https://doi.org/10.1021/acs.oprd.4c00320","url":null,"abstract":"Selecting the development form of an active pharmaceutical ingredient (API) in drug development is key to determining the final performance of the drug substance and drug product. Form selection requires an interdisciplinary approach involving a complex process to discover, monitor, and evaluate the solid-state characteristics, biopharmaceutical properties, stability, and processability of numerous forms. This Perspective discusses the importance of aligning critical material attributes with the desired quality target product profile to ensure drug safety and efficacy. It discusses how the form selection strategy is dependent on factors related to the administration route, dosage form, and therapeutic indication and provides an interdisciplinary framework with four prioritized sets of target attributes for oral delivery: solid-state properties, biopharmaceutical performance, stability, and processability. A classification system to guide form selection, particularly for immediate-release oral medications, is reviewed. The benefits of crystalline forms in terms of stability and processability are highlighted, emphasizing the role of solution crystallization in controlling their development. The interdisciplinary form selection process will be demonstrated through case studies highlighting how each set of target attributes were evaluated leading to the selection of ideal forms for development.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 2","pages":"237–254 237–254"},"PeriodicalIF":3.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Application of an Interdisciplinary Approach to Form Selection in Drug Development

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-01-25 DOI: 10.1021/acs.oprd.4c00320

Darren L. Reid, Margaret M. Faul, Vilmalí López-Mejías, Prashant Agarwal, Markus Bergauer, Laura E. Blue, Mary K. Chaves, John Chung, Melanie Cooke, Robert P. Farrell, James E. Huckle, Ron C. Kelly, Y.-H. Kiang, Weikun Li, Adrian Ortiz, Qiong Wu

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引用次数: 0

A Confined Impinging Jet Reactor for High-Throughput Continuous Flow Mononitration of Salicylic Acid 用于水杨酸高通量连续流单硝的密闭冲击射流反应器

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-01-23 DOI: 10.1021/acs.oprd.4c00467

Muzammilanwar S. Khan, Tabrez R. Shaikh, Sphurti P. Kulkarni, Abhishek A. Patil, Amol A. Kulkarni

{"title":"A Confined Impinging Jet Reactor for High-Throughput Continuous Flow Mononitration of Salicylic Acid","authors":"Muzammilanwar S. Khan, Tabrez R. Shaikh, Sphurti P. Kulkarni, Abhishek A. Patil, Amol A. Kulkarni","doi":"10.1021/acs.oprd.4c00467","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00467","url":null,"abstract":"Novel approach is reported for highly efficient continuous mononitration of salicylic acid using confined impinging jet reactor (CIJR) with a vent. Initially, controlled semibatch reactions are optimized to achieve complete conversion and formation of mononitro products with very high selectivity for 5-nitrosalicylic acid (5-NSA). Further, the combination of computational fluid dynamics simulations and experiments is employed to optimize CIJR design and operating flow conditions, suitable to yield only mononitro products with excellent control over mixing, heat transfer, and liberation of fumes during continuous flow reaction. Detailed analysis of internal flow patterns, rate of heat generation, and concentration distribution inside the CIJR facilitated the optimization of present exothermic reaction in a safe manner. In less than a minute, complete salicylic acid (SA) conversion with good yield and better selectivity for 5-NSA is achieved using the CIJR. Safety and clogging issues are addressed effectively, even at a relatively lower mole ratio (1:5) of SA:acetic acid (AcOH). The present approach is quite scalable using the numbering-up strategy, with advantages viz. nonfouling, high throughput, and the small footprint of CIJR.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"74 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Applicability of Fluidized Bed Crystallization for Separation of Enantiomers Forming Needle-Shaped Crystals

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-01-23 DOI: 10.1021/acs.oprd.4c00444

Jonathan Gänsch, Igor Gamm, Andreas Seidel-Morgenstern, Heike Lorenz

引用次数: 0

Applicability of Fluidized Bed Crystallization for Separation of Enantiomers Forming Needle-Shaped Crystals

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-01-23 DOI: 10.1021/acs.oprd.4c0044410.1021/acs.oprd.4c00444

Jonathan Gänsch*, Igor Gamm, Andreas Seidel-Morgenstern and Heike Lorenz,

{"title":"Applicability of Fluidized Bed Crystallization for Separation of Enantiomers Forming Needle-Shaped Crystals","authors":"Jonathan Gänsch*, Igor Gamm, Andreas Seidel-Morgenstern and Heike Lorenz, ","doi":"10.1021/acs.oprd.4c0044410.1021/acs.oprd.4c00444","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00444https://doi.org/10.1021/acs.oprd.4c00444","url":null,"abstract":"Enantioselective fluidized bed crystallization (FBC) presents an attractive process concept for the separation of chiral compounds due to its continuous operation, high productivity, and narrow size distribution achievable. Here, we report the application related to the amino acid dl-threonine, characterized by a needle-like crystal shape when crystallized from aqueous solution. After demonstrating successful chiral resolution via FBC, the impact of the system’s specific crystal growth kinetics on the FBC performance is studied at pilot plant scale. The coupling of the anisotropic crystal growth with size-classification and fragmentation in the seeding bypass enables the continuous production of compact pure enantiomer crystals with narrow size distribution. The optimization potential of the seeding strategy and the flow rate on separation performance, product crystal shape, and process robustness is investigated as well.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 2","pages":"430–439 430–439"},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.oprd.4c00444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Confined Impinging Jet Reactor for High-Throughput Continuous Flow Mononitration of Salicylic Acid

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-01-23 DOI: 10.1021/acs.oprd.4c0046710.1021/acs.oprd.4c00467

Muzammilanwar S. Khan, Tabrez R. Shaikh, Sphurti P. Kulkarni, Abhishek A. Patil and Amol A. Kulkarni*,

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引用次数: 0

Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-01-22 DOI: 10.1021/acs.oprd.4c0039910.1021/acs.oprd.4c00399

Nicole M. Ralbovsky*, Gunjan Dixit, Justin P. Lomont, Jay Desai, Cristina Butu, Anumita Saha-Shah, Emily Costello, Janelle Lukens, Michael Mazur, Patrick M. McHugh, Rodell C. Barrientos, Andrew Semple, Gregory J. Hughes, Rebecca Chmielowski, Sheng-Ching Wang, Bhumit A. Patel and Joseph P. Smith,

{"title":"Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions","authors":"Nicole M. Ralbovsky*, Gunjan Dixit, Justin P. Lomont, Jay Desai, Cristina Butu, Anumita Saha-Shah, Emily Costello, Janelle Lukens, Michael Mazur, Patrick M. McHugh, Rodell C. Barrientos, Andrew Semple, Gregory J. Hughes, Rebecca Chmielowski, Sheng-Ching Wang, Bhumit A. Patel and Joseph P. Smith, ","doi":"10.1021/acs.oprd.4c0039910.1021/acs.oprd.4c00399","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00399https://doi.org/10.1021/acs.oprd.4c00399","url":null,"abstract":"Process analytical technology (PAT) is increasingly being explored within pharmaceutical production and process development, with a particular emphasis in the vaccine and biologics space. PAT aims to provide increased process understanding and control through real-time monitoring of critical quality attributes and key process parameters as well as detection of process deviations. Downstream purification in pharmaceutical manufacturing processes can be complex and requires copious analytical characterization. Herein, we showcase the successful implementation of PAT for monitoring bioconjugation reactions related to both vaccine and biologic pharmaceutical manufacturing processes. Specifically, we explore a variety of PAT-based techniques and their utility for monitoring polysaccharide–protein and protein–small molecule bioconjugation reactions. PAT applications using at-line multiangle light scattering, in situ fluorescence spectroscopy, in situ viscosity, and at-line hydrophobic interaction chromatography are shown to each provide distinct, real-time analytical information to enhance the understanding and characterization of bioconjugation reactions.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 2","pages":"353–362 353–362"},"PeriodicalIF":3.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions 药物生物偶联反应实时监测的过程分析技术

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-01-22 DOI: 10.1021/acs.oprd.4c00399

Nicole M. Ralbovsky, Gunjan Dixit, Justin P. Lomont, Jay Desai, Cristina Butu, Anumita Saha-Shah, Emily Costello, Janelle Lukens, Michael Mazur, Patrick M. McHugh, Rodell C. Barrientos, Andrew Semple, Gregory J. Hughes, Rebecca Chmielowski, Sheng-Ching Wang, Bhumit A. Patel, Joseph P. Smith

{"title":"Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions","authors":"Nicole M. Ralbovsky, Gunjan Dixit, Justin P. Lomont, Jay Desai, Cristina Butu, Anumita Saha-Shah, Emily Costello, Janelle Lukens, Michael Mazur, Patrick M. McHugh, Rodell C. Barrientos, Andrew Semple, Gregory J. Hughes, Rebecca Chmielowski, Sheng-Ching Wang, Bhumit A. Patel, Joseph P. Smith","doi":"10.1021/acs.oprd.4c00399","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00399","url":null,"abstract":"Process analytical technology (PAT) is increasingly being explored within pharmaceutical production and process development, with a particular emphasis in the vaccine and biologics space. PAT aims to provide increased process understanding and control through real-time monitoring of critical quality attributes and key process parameters as well as detection of process deviations. Downstream purification in pharmaceutical manufacturing processes can be complex and requires copious analytical characterization. Herein, we showcase the successful implementation of PAT for monitoring bioconjugation reactions related to both vaccine and biologic pharmaceutical manufacturing processes. Specifically, we explore a variety of PAT-based techniques and their utility for monitoring polysaccharide–protein and protein–small molecule bioconjugation reactions. PAT applications using at-line multiangle light scattering, in situ fluorescence spectroscopy, in situ viscosity, and at-line hydrophobic interaction chromatography are shown to each provide distinct, real-time analytical information to enhance the understanding and characterization of bioconjugation reactions.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"27 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quality Control for Incoming Raw Materials Beyond Identity and Purity: Case Studies from Recent Merck API Manufacturing Processes

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-01-19 DOI: 10.1021/acs.oprd.4c0042310.1021/acs.oprd.4c00423

Nelo R. Rivera*, Rekha Gangam*, Rebecca Arvary, Taylor Behre, Zhiwei Chen, Erik D. Guetschow, Nadine Kuhl, Mingxiang Lin, Nastaran Salehi Marzijarani, Erin McCarthy, Ji Qi, Ben W. H. Turnbull, Tao Wang and Wenjun Liu*,

{"title":"Quality Control for Incoming Raw Materials Beyond Identity and Purity: Case Studies from Recent Merck API Manufacturing Processes","authors":"Nelo R. Rivera*, Rekha Gangam*, Rebecca Arvary, Taylor Behre, Zhiwei Chen, Erik D. Guetschow, Nadine Kuhl, Mingxiang Lin, Nastaran Salehi Marzijarani, Erin McCarthy, Ji Qi, Ben W. H. Turnbull, Tao Wang and Wenjun Liu*, ","doi":"10.1021/acs.oprd.4c0042310.1021/acs.oprd.4c00423","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00423https://doi.org/10.1021/acs.oprd.4c00423","url":null,"abstract":"The development of robust manufacturing processes for active pharmaceutical ingredients (APIs) is paramount to ensure a supply of safe and effective medications. Implementation of a holistic control strategy, including quality control of incoming raw materials, is a key element in meeting this goal. This paper describes several examples from recent Merck API manufacturing routes, in which impurities in raw materials affected the processes in various ways, including giving rise to new process impurities, jeopardizing process safety and causing damage to reaction vessels, and─sometimes unexpectedly and counterintuitively─suppressing formation of process impurities. In all of these examples, analytical characterization plays a critical role in identifying these impurities and enabling their control to ensure consistent process performance and product quality.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 2","pages":"401–410 401–410"},"PeriodicalIF":3.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quality Control for Incoming Raw Materials Beyond Identity and Purity: Case Studies from Recent Merck API Manufacturing Processes 入厂原材料的质量控制不仅限于特性和纯度：默克近期原料药生产工艺案例研究

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-01-19 DOI: 10.1021/acs.oprd.4c00423

Nelo R. Rivera, Rekha Gangam, Rebecca Arvary, Taylor Behre, Zhiwei Chen, Erik D. Guetschow, Nadine Kuhl, Mingxiang Lin, Nastaran Salehi Marzijarani, Erin McCarthy, Ji Qi, Ben W. H. Turnbull, Tao Wang, Wenjun Liu

引用次数: 0