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Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders

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Abstract

Continuous manufacturing (CM) has clear potential for manufacturing solid oral dosages. It provides several advantages that may aid the manufacturing and quality of drug products. However, one of the main challenges of this technology is the relatively large amount of knowledge required and the amounts of material needed to develop the process during the early stages of development. Early process development evaluations of continuous manufacturing equipment often require larger amounts of material compared with batch, which hinder CM prospect for drugs during the early stages of process development. In this work, a small-scale evaluation of the mixing process occurring in a continuous mixing system was performed. The evaluation involved the use of a small-scale “mixing cell” which was able to replicate the lubrication process of a continuous mixer. It is worth mentioning that we designed the mixing cell by reconfiguration of an existing continuous tubular blender. The extent of lubrication evaluation was performed for three example formulations and was done by mimicking the amount of shear provided to a formulation by means of matching the number of paddle-passes that a formulation experiences within a continuous blending process in the batch mixing cell. The evaluation showed that the small-scale mixing cell was able to replicate the extent of lubrication—evaluated by measuring the tensile strength of compacts being made with both the continuous and mixing cell experiments—occurring in the continuous mixer using a fraction of the amount of materials needed to perform the same evaluation in the continuous blending process.

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Acknowledgments

The authors would like to thank Mr. Lan Le, Mr. Kian Chau, Ms. Rhea Jamsandekar, and Ms. Tulsi Char for their support during the experiments. The authors also want to thank Dr. James Scicolone, Dr. Sonia Razavi and, Dr. Sarang Oka for their valuable inputs.

Equation parameters

  • MAcc mass hold up inside of the blender [=] g

  • \( {\dot{m}}_{in} \) mass flow rate into the blender [=] g/s

  • \( {\dot{m}}_{out} \) mass flow rate out of the blender [=] g/s

  • τspace − time space time in the blender [=] s

  • Nblade − passes number of blade passes experienced by the blend inside the blender

  • ω angular speed of blades in the blender [=] RPM

  • Kbatch extent of lubrication in a batch blending system [=] dm

  • δ geometric constant for extent of lubrication in batch systems [=] unitless

  • Vb batch blender volume [=] L

  • Fh fraction of headspace empty [=] unitless

  • Nrev number of revolutions of the blende [=] unitless

  • Kcontinuous extent of lubrication in continuous blending systems [=] dm

  • α geometric constant for extent of lubrication in continuous systems [=] unitless

  • vtip tip speed of blades in the continuous blending system [=] m/s

  • Dblender dimeter of the continuous blending system [=] m

  • Ksystem extent of lubrication observed by the blend [=] dm

  • σtablet, 0 tablet tensile strength at point of no lubrication [=] MPa

  • σtablet tablet tensile strength [=] MPa

  • γ lubrication extent coefficient of a blend [=] unitless

  • μ tensile strength decay rate of a blend [=] 1/dm

  • F tablet breaking force [=] N or kp

  • hT measured tablet thickness [=] mm

  • Dtablet tablet in-die diameter [=] mm

Funding

The research was financially supported by Janssen Pharmaceuticals.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, California State University, Long Beach, California, USA

    Sara Moghtadernejad

  2. Department of Chemical and Biochemical Engineering. Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA

    M. Sebastian Escotet-Espinoza, Zhanjie Liu, Elisabeth Schäfer & Fernando Muzzio

  3. The Janssen Pharmaceutical Companies of Johnson and Johnson, Beerse, Belgium

    Elisabeth Schäfer

Authors
  1. Sara Moghtadernejad
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  2. M. Sebastian Escotet-Espinoza
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  4. Elisabeth Schäfer
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  5. Fernando Muzzio
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Corresponding authors

Correspondence to Sara Moghtadernejad or Fernando Muzzio.

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Sara Moghtadernejad and M. Sebastian Escotet-Espinoza share equal first authorship.

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Moghtadernejad, S., Escotet-Espinoza, M.S., Liu, Z. et al. Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders. AAPS PharmSciTech 20, 262 (2019). https://doi.org/10.1208/s12249-019-1473-1

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