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

  • Balázs Démuth 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 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 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 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 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 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 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 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 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 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 Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • Tibor Nagy Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • Attila Bódis Formulation R&D, Gedeon Richter Plc., H-1103 Budapest, Gyömrői utca 19-21., Hungary
  • György Marosi 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 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

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
Published online
2020-03-23
How to Cite
[1]
Démuth, B., Fülöp, G., Kovács, M., Madarász, L., Ficzere, M., Köte, Ákos, Szabó, B., Nagy, B., Balogh, A., Csorba, K., Kaszás, G., Nagy, T., Bódis, A., Marosi, G. and Nagy, Z. ONLINE. Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation. Periodica Polytechnica Chemical Engineering. (ONLINE). https://doi.org/10.3311/PPch.14972.
Section
Articles