Selectivity Control by Use of Near-IR for a Hydrogenation Process

Smet, Koen De; Dun, Jan Van; Stokbroekx, Bard; Spittaels, Tom; Schroyen, Christine; Broeck, Peter Van den; Lambrechts, J.F.; Cleuvenbergen, Dirk Van; Smout, Guy; Dubois, J.-L.; Horváth, András; Verbraeken, Jurgen; Cuypers, Jef

doi:10.1021/op049782x

Cited by 13 publications

(13 citation statements)

References 2 publications

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“…In recent years, some particle analysis techniques (PATs) have been widely used to monitor and control the transformation process during crystallization, especially in pharmaceutical, fine chemical, and food industries. , Off-line techniques such as powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermo gravimetric analysis (TGA), and scanning electron microscopy (SEM) are often used to identify the polymorphs to qualitatively analyze this process. , In situ techniques including focused beam reflectance measurement (FBRM), Raman spectroscopy, , attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), and near-infrared (NIR) spectroscopy can be applied to analyze the transformation kinetics quantitatively. Particle vision measurement (PVM) can be used to follow the evolution of crystal morphology during the process.…”

Section: Introductionmentioning

confidence: 99%

Solution-Mediated Polymorphic Transformation: From Amorphous to Crystals of Disodium Guanosine 5′-Monophosphate in Ethanol

Zou¹,

Qiao²,

Yang³

et al. 2017

Ind. Eng. Chem. Res.

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Solvent-mediated transformation of disodium guanosine 5′-monophosphate (5′-GMPNa2) from amorphous to hydrated crystal phases was studied. The SMT process is dominated by the dissolution of the amorphous form and nucleation and growth of the crystal polymorph. The kinetic estimation based on population balance equation was carried out according to experimental data, including polymorphic fraction in the solid phase, solute concentration, and crystal size distribution. Furthermore, independent seeded batch experiments were carried out to estimate the kinetic parameters. The experimental data showed that the nucleation and growth of the crystal polymorph occurred shortly after the dissolution of the amorphous form. The estimated growth, nucleation, and dissolution rates indicated that the solution-mediated transformation was governed by the nucleation and growth of crystal polymorph. We believe that the results hold great importance toward understanding the transformation process of 5′-GMPNa2, which provides theoretical guidance for producing its specific forms, and possibly those for other pharmaceuticals and chemicals as well.

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Section: Introductionmentioning

confidence: 99%

Solution-Mediated Polymorphic Transformation: From Amorphous to Crystals of Disodium Guanosine 5′-Monophosphate in Ethanol

Zou¹,

Qiao²,

Yang³

et al. 2017

Ind. Eng. Chem. Res.

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“…In 2005, a series of articles in a special section of the journal Organic Process Research & Development (OPR&D) demonstrated the potential of PAT framework in various operations within pharmaceutical process development and manufacturing. These articles cover reaction monitoring [161][162][163][164] crystallization, 161,165 granulation, 161 calorimetry and safety studies, 163 and in situ cleaning validation. 166 Since then, OPR&D had served as a regular platform for reporting new PAT technologies and applications.…”

Section: Publications Conferences and Internetmentioning

confidence: 99%

Trends in process analytical technology

2010

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Since the promotion of Process Analytical Technology (PAT) by the U.S. Food and Drug Administration (FDA), there has been a flurry of activities happening across related fields. This excitement permeates regulatory agencies, professional societies, academia and industry worldwide. This review surveys the PAT related developments that have taken place in the period 2004-2009. It serves as an introduction to PAT, with highlights on the parallel advances and convergence points across various fields and applications. From this review, five common threads are identified from the underlying trends of the recent global PAT endeavor, namely, organisational objectives, enabling sciences, economic outlook, collaborative efforts and emerging trends. There are also six potential gaps that require further efforts to bridge. The overall PAT venture is promising for delivering an integrated systems approach for quality design, process analyses, understanding and control, continuous improvement, knowledge and risk-based management within the FDA 21st century pharmaceutical cGMP initiative.

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“…They also provide continuous real-time monitoring and are much more amenable to use in large scale manufacturing. 5,6 Whatever measurement system is used, the aim is clear, to gain process understanding and develop robust processes such that in-process measurements are only required where benefits can be realised, such as controlling critical process parameters and potentially reduce end product testing. Therefore, many of the measurement systems used in process development can often become embedded in the control strategy for a manufacturing process, so it is important that the measurement system itself is reliable and robust.…”

Section: Introductionmentioning

confidence: 99%

“…Techniques such as MS, NMR and HPLC can provide detailed process understanding in early stages of development and are widely used, mostly off-line but increasingly using more at-line and on-line modes. − Optical spectroscopic techniques can also be used as in-line measurement systems and offer some advantages over traditional off-line techniques for processes that are difficult to sample (heterogeneous, low temperature, unstable intermediates). They also provide continuous real-time monitoring and are much more amenable to use in large scale manufacturing. , Whatever measurement system is used, the aim is clear, to gain process understanding and develop robust processes such that in-process measurements are only required where benefits can be realised, such as controlling critical process parameters and potentially reduce end product testing. Therefore, many of the measurement systems used in process development can often become embedded in the control strategy for a manufacturing process, so it is important that the measurement system itself is reliable and robust.…”

Section: Introductionmentioning

confidence: 99%

In situ Monitoring of a Heterogeneous Etherification Reaction Using Quantitative Raman Spectroscopy

Hart

Pedge

Steven

et al. 2014

Org. Process Res. Dev.

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The development and use of an in situ Raman spectroscopic method for the end-point detection of an etherification reaction, during a pilot plant scale manufacturing campaign, is described. Monitoring the reaction progress and minimising the level remaining of a chloropyrazine starting material at the reaction end-point were important, as the latter impacted a drug substance critical quality attribute (CQA). Furthermore, the etherification reaction required the use of a heterogeneous base (K 2 CO 3 ), and therefore the time to reach reaction completion could be scale dependent, owing to differences in reactor geometry and mixing characteristics. To provide valuable process understanding about the rate and extent of reaction during scale-up, a quantitative method utilising in situ Raman spectroscopy was developed. A series of laboratory scale reactions were performed to provide the spectroscopic and off-line reference measurements (HPLC) required for calibration model development. A quantitative multivariate calibration (PLS2) was developed to allow the concentration of starting material and reaction product to be predicted during the final 30% of the reaction using in situ generated Raman spectra. The root-mean square error of prediction (RMSEP) values for the 5-factor PLS2 model were 0.2% w/w and 0.1% w/w for ether 1 and phenol 2 respectively. This method was transferred and implemented in the pilot plant to detect the reaction end-point for a number of batches. During the initial batches, it was demonstrated that the results obtained from the Raman calibration model were equivalent to results obtained by off-line HPLC analysis. OPC was used to transfer the predicted results to the pilot plant control system, thus allowing scientists to remotely view the reaction progress in real-time.

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Selectivity Control by Use of Near-IR for a Hydrogenation Process

Cited by 13 publications

References 2 publications

Solution-Mediated Polymorphic Transformation: From Amorphous to Crystals of Disodium Guanosine 5′-Monophosphate in Ethanol

Solution-Mediated Polymorphic Transformation: From Amorphous to Crystals of Disodium Guanosine 5′-Monophosphate in Ethanol

Trends in process analytical technology

In situ Monitoring of a Heterogeneous Etherification Reaction Using Quantitative Raman Spectroscopy

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