The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Thomas De Beer - One of the best experts on this subject based on the ideXlab platform.

  • control of three different Continuous pharmaceutical manufacturing processes use of soft sensors
    International Journal of Pharmaceutics, 2018
    Co-Authors: Jakob Rehrl, Martin Horn, Anssi-pekka Karttunen, Niels Nicolai, Theresa Hormann, Ossi Korhonen, Thomas De Beer, Ingmar Nopens, Johannes Khinast
    Abstract:

    One major advantage of Continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the measurement of active pharmaceutical ingredient (API) concentration at specific locations in the production line via process analytic technology (PAT), e.g. near-infrared (NIR) spectrometers. The implementation of the PAT instruments is associated with monetary investment and the long term operation requires techniques avoiding sensor drifts. Therefore, our paper proposes a soft sensor approach for predicting the API concentration from the feeder data. In addition, this information can be used to detect sensor drift, or serve as a replacement/supplement of specific PAT equipment. The paper presents the experimental determination of the residence time distribution of selected unit operations in three different Continuous Processing lines (hot melt extrusion, direct compaction, wet granulation). The mathematical models describing the soft sensor are developed and parameterized. Finally, the suggested soft sensor approach is validated on the three mentioned, different Continuous Processing lines, demonstrating its versatility.

  • Process Analytical Technology for Continuous manufacturing of solid-dosage forms
    TrAC - Trends in Analytical Chemistry, 2015
    Co-Authors: Margot Fonteyne, Bernd Van Snick, Jean Paul Remon, Fien De Leersnyder, Jurgen Vercruysse, Chris Vervaet, Thomas De Beer
    Abstract:

    Currently, pharmaceutical production is making the switch from batch Processing towards Continuous Processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the advantages of Continuous Processing, so the critical quality attributes of Continuously produced pharmaceuticals need to be monitored in real time. In 2004, the US Food and Drug Administration launched the process analytical technology (PAT) concept to stimulate the pharmaceutical industry to change from off-line to real-time quality testing. This review explores the implementation of PAT tools within Continuous pharmaceutical processes (i.e., blending, spray drying, roller compaction, twin-screw granulation and compression), focusing on both opportunities and challenges.

Andrew B Holmes - One of the best experts on this subject based on the ideXlab platform.

  • a gram scale batch and flow total synthesis of perhydrohistrionicotoxin
    Chemistry: A European Journal, 2010
    Co-Authors: Malte Brasholz, James M Macdonald, John H Ryan, Simon Saubern, Andrew B Holmes
    Abstract:

    : The total synthesis of the spiropiperidine alkaloid (-)-perhydrohistrionicotoxin (perhydro-HTX) 2 has been accomplished on a gram scale by employing both conventional batch chemistry as well as microreactor techniques. (S)-(-)-6-Pentyltetrahydro-pyran-2-one 8 underwent nucleophilic ring opening to afford the alcohol 10, which was elaborated to the nitrone 13. Protection of the nitrone as the 1,3-adduct of styrene and side-chain extension to the unsaturated nitrile afforded a precursor 17, which underwent dipolar cycloreversion and 1,3-dipolar cycloaddition to give the core spirocyclic precursor 18 that was converted into perhydro-HTX 2. The principal steps to the spirocycle 18 have successfully been transferred into flow mode by using different types of microreactors and in a telescoped fashion, allowing for a more rapid access to the histrionicotoxins and their analogues by Continuous Processing.

Johannes Khinast - One of the best experts on this subject based on the ideXlab platform.

  • control of three different Continuous pharmaceutical manufacturing processes use of soft sensors
    International Journal of Pharmaceutics, 2018
    Co-Authors: Jakob Rehrl, Martin Horn, Anssi-pekka Karttunen, Niels Nicolai, Theresa Hormann, Ossi Korhonen, Thomas De Beer, Ingmar Nopens, Johannes Khinast
    Abstract:

    One major advantage of Continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the measurement of active pharmaceutical ingredient (API) concentration at specific locations in the production line via process analytic technology (PAT), e.g. near-infrared (NIR) spectrometers. The implementation of the PAT instruments is associated with monetary investment and the long term operation requires techniques avoiding sensor drifts. Therefore, our paper proposes a soft sensor approach for predicting the API concentration from the feeder data. In addition, this information can be used to detect sensor drift, or serve as a replacement/supplement of specific PAT equipment. The paper presents the experimental determination of the residence time distribution of selected unit operations in three different Continuous Processing lines (hot melt extrusion, direct compaction, wet granulation). The mathematical models describing the soft sensor are developed and parameterized. Finally, the suggested soft sensor approach is validated on the three mentioned, different Continuous Processing lines, demonstrating its versatility.

  • Continuous Processing of active pharmaceutical ingredients suspensions via dynamic cross flow filtration
    Journal of Pharmaceutical Sciences, 2015
    Co-Authors: Johannes Gursch, Roland Hohl, Gregor Toschkoff, Diana Dujmovic, Jorg Brozio, Norbert Rasenack, Markus Krumme, Johannes Khinast
    Abstract:

    ABSTRACT Over the last years, Continuous manufacturing has created significant interest in the pharmaceutical industry. Continuous filtration at low flow rates and high solid loadings poses, however, a significant challenge. A commercially available, Continuously operating, dynamic cross-flow filtration device (CFF) is tested and characterized. It is shown that the CFF is a highly suitable technology for Continuous filtration. For all tested model active pharmaceutical ingredients, a material-specific strictly linear relationship between feed and permeate rate is identified. Moreover, for each tested substance, a constant concentration factor is reached. A one-parameter model based on a linear equation is suitable to fully describe the CFF filtration performance. This rather unexpected finding and the concentration polarization layer buildup is analyzed and a basic model to describe the observed filtration behavior is developed. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3481-3489, 2015

Ian R Baxendale - One of the best experts on this subject based on the ideXlab platform.

  • studies of a diastereoselective electrophilic fluorination reaction employing a cryo flow reactor
    Synlett, 2013
    Co-Authors: Keiji Nakayama, Duncan L Browne, Ian R Baxendale
    Abstract:

    The application of meso-scale flow chemistry in research laboratories continues to increase. Here, we report on the use of a modular cryo-flow device as applied to a diastereoselective fluorination process. The reactor can be incorporated into existing flow chemistry setups to permit Continuous Processing at low temperatures without recourse to cryogenic consumables.

  • Continuous flow Processing of slurries evaluation of an agitated cell reactor
    Organic Process Research & Development, 2011
    Co-Authors: Duncan L Browne, Benjamin J Deadman, Robert Ashe, Ian R Baxendale
    Abstract:

    A general method for the Continuous Processing of suspensions and particulates is reported. A commercially available agitating cell reactor which uses a transverse mixing motion to maintain solids in suspension has been successfully applied to a salt-forming reaction. The flow device delivered 208 g of N-iodomorpholinium hydroiodide salt over a 9-h period (equating to 3.88 kg/week) under optimized conditions. The reactor is suitable for the medium-scale (5 kg) Processing of solid-forming reactions and appears to offer the potential for a variety of more complex applications.

Martyn Poliakoff - One of the best experts on this subject based on the ideXlab platform.

  • Continuous catalytic reactions in supercritical fluids
    Applied Catalysis A-general, 2001
    Co-Authors: Jason R Hyde, Peter Licence, Daniel Carter, Martyn Poliakoff
    Abstract:

    Abstract Recent heightened awareness of the environmental impacts associated with a large proportion of established chemical processes has led to the application of considerable pressures on the chemical industry, both regulatory and consumer driven, to adopt a cleaner and greener approach to manufacture. The economies of scale and associated efficiencies of Continuous processes have long been a contributing factor in the design and efficient running of many large-scale industrial plants. When successfully combined with a versatile and environmentally benign solvent system such as supercritical fluids (SCFs), Continuous Processing can be seen to be suitable for a wide variety of reactions (hydrogenation, hydroformylation, alkylation, etc.). which can be conducted efficiently in an environmentally sensitive way. This review article aims to show the reader how the marriage of these two technologies is helping chemistry to achieve this goal.