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  1. Real-time feasible model-based crystal size and shape control of crystallization processes

    09 Jun 2023 | Contributor(s):: Szilagyi, Botond, Nagy, Zoltan K.

    The simultaneous control of crystal size and shape is particularly important in fine chemical and pharmaceutical crystallization. These two quantities influence the dissolution rate and bioavailability of final drug products, and also contribute to the manufacturability and efficiency of...

  2. Progress of Pharmaceutical Continuous Crystallization

    09 Jun 2023 | Contributor(s):: Zhang, DJ, Xu, SJDu, SC, Wang, JK, Gong, JB

    Crystallization is an important unit operation in the pharmaceutical industry. At present, most pharmaceutical crystallization processes are performed in batches. However, due to product variability from batch to batch and to the low productivity of batch crystallization, continuous...

  3. Progress to Date in the Design and Operation of Continuous Crystallization Processes for Pharmaceutical Applications

    09 Jun 2023 | Contributor(s):: Wood, Barbara, Girard, Kevin, Polster, Christopher, Croker, Denise

    Continuous crystallization has gained interest in the pharmaceutical sector as part of the drive toward thetransition from exclusive batch manufacturing to integrated continuous manufacturing in this industry. As a result, the design and operation of continuous crystallization processes for the...

  4. Process Analytical Technology for continuous manufacturing of solid-dosage forms

    09 Jun 2023 | Contributor(s):: Fonteyne, Margot;, Vercrusysse, Jurgen, De Leersnyder, Fien, Van Snick, Bernd, Vervaet, Chris, Remon, Jean, De Beer, Thomas

    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...

  5. Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients

    09 Jun 2023 | Contributor(s):: Malwade, CR, Qu, HY

    Background: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities....

  6. Process Analytical Technology Tools for Monitoring Pharmaceutical Unit operations: A Control Strategy for Continuous Process Verification

    09 Jun 2023 | Contributor(s):: Kim, Eun, Kim, Ji, Kim, Min-Soo, Jeong, Seong, Choi, Du

    Various frameworks and methods, such as quality by design (QbD), real time release test (RTRT), and continuous process verification (CPV), have been introduced to improve drug product quality in the pharmaceutical industry. The methods recognize that an appropriate combination of process controls...

  7. Pharmaceutical industry perspectives on flow chemocatalysis and biocatalysis

    09 Jun 2023 | Contributor(s):: Martin, LL, Peschke, TVenturoni, F, Mostarda, S

    In response to a growing demand for more sustainable and cost-effective synthetic processes, the pharmaceutical industry is increasingly relying on continuous manufacturing as a valuable alternative to conventional batch processing. Particularly, flow processing may enable process intensification...

  8. Pharmaceutical spray drying: solid-dose process technology platform for the 21st century

    09 Jun 2023 | Contributor(s):: Snyder, HE

    Requirement for precise control of solid-dosage particle properties created with a scalable process technology are continuing to expand in the pharmaceutical industry. Alternate methods of drug delivery, limited active drug substance solubility and the need to improve drug product stability under...

  9. Perspectives on the flexibility analysis for continuous pharmaceutical manufacturing processes

    09 Jun 2023 | Contributor(s):: Yang, WH, Qian, WXYuan, ZH, Chen, BZ

    Pharmaceutical continuous manufacturing, especially under the context of COVID-19 pandemic, is regarded as an emerging technology that can guarantee the adequate quality assurance and mitigate process risk while guaranteeing the desirable economic performance. Flexibility analysis is one approach...

  10. Pharmaceutical application of multivariate modelling techniques: a review on the manufacturing of tablets

    09 Jun 2023 | Contributor(s):: Shi, Guolin, Lin, Longfei, Liu, Yuling, Chen, Gongsen, Luo, Yuting, Wu, Yanqiu, Li, Hui

    The tablet manufacturing process is a complex system, especially in continuous manufacturing (CM). It includes multiple unit operations, such as mixing, granulation, and tableting. In tablet manufacturing, critical quality attributes are influenced by multiple factorial relationships between...

  11. Pharmaceutical cocrystallization techniques. Advances and challenges

    09 Jun 2023 | Contributor(s):: Rodrigues, M, Baptista, BLopes, JA, Sarraguca, MC

    Cocrystals are homogenous (single-phase) crystalline structures composed by two or more components in a definite stoichiometric ratio bonded together by noncovalent bonds. Pharmaceutical industry has been showing interest in cocrystals due to their ability to improve active pharmaceutical...

  12. Part 3: Enhanced Approaches to the Development of the Control Strategy and its Implementation in the Manufacturing Process Description

    09 Jun 2023 | Contributor(s):: Popkin, ME, Omer, BASeibert, KD, Luciani, CV, Srivastava, S, Hobson, L, Lepore, JV

    A series of case histories from IQ consortium member companies will be presented to exemplify how the application of the ICH Q11 vision for enhanced Quality by Design (QbD) development of the active pharmaceutical ingredient (API) can lead to differentiated outcomes for elements such as the API...

  13. PAT implementation for advanced process control in solid dosage manufacturing - A practical guide

    09 Jun 2023 | Contributor(s):: Sacher, Stephan, Poms, Johannes, Rehrl, Jakob, Khinast, Johannes G.

    The implementation of continuous pharmaceutical manufacturing requires advanced control strategies rather than traditional end product testing or an operation within a small range of controlled parameters. A high level of automation based on process models and hierarchical control concepts is...

  14. Oscillatory Flow Reactors (OFRs) for Continuous Manufacturing and Crystallization

    09 Jun 2023 | Contributor(s):: McGlone, Thomas, Briggs, Naomi E. B., Clark, Catriona A., Brown, Cameron J., Sefcik, Jan, Florence, Alastair J.

    Continuous crystallization is an attractive approach for the delivery of consistent particles with specified critical quality attributes (CQAs), which are attracting increased interest for the manufacture of high value materials, including fine chemicals and pharmaceuticals. Oscillatory flow...

  15. Near-infrared spectroscopic applications in pharmaceutical particle technology

    09 Jun 2023 | Contributor(s):: Razuc, M, Grafia, AGallo, L, Ramirez-Rigo, MV, Romanach, RJ

    Near-infrared spectroscopy (NIRS) is nowadays an established analytical technique in the pharmaceutical industry. The aim of this review is to present the progress of NIRS in providing useful information for pharmaceutical particle technology. NIR methods are now developed to characterize a wide...

  16. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes

    09 Jun 2023 | Contributor(s):: De Beer, Thomas, Burggraeve, Anneleen, Fonteyne, Margot, Saerens, Lien, Remon, Jean Paul, Vervaet, Chris;

    Within the Process Analytical Technology (PAT) framework, it is of utmost importance to obtain critical process and formulation information during pharmaceutical processing. Process analyzers are the essential PAT tools for real-time process monitoring and control as they supply the data from...

  17. Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production

    09 Jun 2023 | Contributor(s):: Lee, SL, O'Connor, TFYang, XC, Cruz, CN, Chatterjee, S, Madurawe, RD, Moore, CMV, Yu, LX, Woodcock, J

    Currently, there is a high level of interest in the pharmaceutical industry in continuous-manufacturing strategies, integrated with online-monitoring tools, that are designed, optimized, and controlled using advanced, model-predictive systems. These strategies can accelerate the full...

  18. Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

    09 Jun 2023 | Contributor(s):: Rogers, Amanda J, Hashemi, Amir, Ierapetritou, Marianthi

    The objective of this work is to present a review of computational tools and models for pharmaceutical processes, specifically those for the continuous manufacture of solid dosage forms. Relevant mathematical methods and simulation techniques are discussed, as is the development of process models...

  19. Micro reactor and flow chemistry for industrial applications in drug discovery and development

    09 Jun 2023 | Contributor(s):: Baraldi, PT, Hessel, V

    In this review, case studies focused on syntheses of active pharmaceutical ingredients, intermediates and lead compounds are reported employing micro reactors and continuous flow technology in areas such as medicinal chemistry, chemical development and manufacturing. The advantages of flow...

  20. Model Based Estimation of 2D Crystallization Kinetics From Concentration and CLD Measurements

    09 Jun 2023 | Contributor(s):: Szilagyi, Botond, Borsos, Akos Simone, Elena Nagy, Zoltan K., Espuña, Antonio, Graells, Moisès, Puigjaner, Luis

    Due to the fact that crystal size and shape influence relevant macroscopic properties of solid particles, the understanding and control of these quantities have increasing importance in particulate science. Crystallization, the primary crystal formation and purification process, is usually...

  21. Model development and prediction of particle size distribution, density and friability of a comilling operation in a continuous pharmaceutical manufacturing process

    09 Jun 2023 | Contributor(s):: Metta, Nirupaplava, Verstraeten, Maxim Ghijs, Michael Kumar, Ashish Schafer, Elisabeth Singh, Ravendra De Beer, Thomas Nopens, Ingmar Cappuyns, Philippe, Van Assche, Ivo

    The comilling process plays an important role in solid oral dosage manufacturing. In this process, the granulated products are comminuted to the required size distribution through collisions created from a rotating impeller. In addition to predicting particle size distribution, there is a need to...

  22. Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production - A critical review

    09 Jun 2023 | Contributor(s):: Kumar, Ashish, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar

    The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete...

  23. Melt extrusion with poorly soluble drugs - An integrated review

    09 Jun 2023 | Contributor(s):: Repka, Michael A., Bandari, Suresh, Kallakunta, Venkata Raman, Vo, Anh Q., McFall, Haley, Pimparade, Manjeet B., Bhagurkar, Ajinkya M.

    Over the last few decades, hot melt extrusion (HME) has emerged as a successful technology for a broad spectrum of applications in the pharmaceutical industry. As indicated by multiple publications and patents, HME is mainly used for the enhancement of solubility and bioavailability of poorly...

  24. Manufacturing of Solid Drug

    09 Jun 2023 | Contributor(s):: Ierapetritou, Marianthi, Escotet-Espinoza, M Sebastian, Singh, Ravendra

    This chapter focuses on the application and development of unit operation and process models of the major routes of continuous solid dose manufacturing. Process models developed in the chapter are very important tools for the design of control system. The chapter also focuses on the current...

  25. Ionic liquids in pharmaceutical industry: A systematic review on applications and future perspectives

    09 Jun 2023 | Contributor(s):: Zhuang, WC, Hachem, KBokov, D, Ansari, MJ, Nakhjiri, AT

    Ionic liquids (ILs) have demonstrated incredible potential of application in various industries such as pharmaceutics. Appropriate utilization of ILs in the pharmaceutical industry can be a great option to overcome the operational/functional challenges related to the use of traditional organic...