Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Authors

  • Balázs Démuth
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Gergő Fülöp
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary; Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • Márk Kovács
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Lajos Madarász
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Máté Ficzere
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Ákos Köte
    Affiliation
    Department of Automation and Applied Informatics, Faculty of Electrical Engineering and Informatics, Budapest University of Technology and Economics, H-1117 Budapest, Magyar Tudósok körútja 2., Hungary
  • Bence Szabó
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Brigitta Nagy
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Attila Balogh
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Kristóf Csorba
    Affiliation
    Department of Automation and Applied Informatics, Faculty of Electrical Engineering and Informatics, Budapest University of Technology and Economics, H-1117 Budapest, Magyar Tudósok körútja 2., Hungary
  • Gábor Kaszás
    Affiliation
    Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • Tibor Nagy
    Affiliation
    Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • Attila Bódis
    Affiliation
    Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • György Marosi
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
  • Zsombor Kristóf Nagy
    Affiliation
    Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rakpart 3., Hungary
https://doi.org/10.3311/PPch.14972

Abstract

Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.
A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated.

Keywords:

Twin-Screw Granulation, low-dose formulation, Content Uniformity, pump characteristics

Citation data from Crossref and Scopus

Published Online

2020-03-23

How to Cite

Démuth, B., Fülöp, G., Kovács, M., Madarász, L., Ficzere, M., Köte, Ákos “Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation”, Periodica Polytechnica Chemical Engineering, 64(4), pp. 391–400, 2020. https://doi.org/10.3311/PPch.14972

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Articles