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Effects of Process and Design Parameters on Granule Size Distribution in a Continuous High Shear Granulation Process

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Abstract

Purpose

Wet granulation is widely used in the pharmaceutical industry. This advantageous technology is capable of enhancing compression and powder handling, decreasing ingredient segregation, and promoting blend and content uniformity. Currently, a high level of interest exists in the continuous version of this technology, both by the US Food and Drug Administration (FDA), and by pharmaceutical manufacturers.

Methods

In this paper, a continuous high shear wet granulation process was examined based on a placebo formulation comprising 70% ∂-lactose monohydrate and 30% microcrystalline cellulose (Avicel® PH101). Granulation was then carried out in a continuous high shear mixer granulator, Glatt GCG 70. The impact of two process variables (rotation speed and liquid/solid (L/S) ratio) and two design parameters (blade configuration and nozzle position) were evaluated via an I-optimal design.

Results

Multi-factor analysis of variance (ANOVA) indicated that rotation speed and L/S ratio dominated the granulation process and had the most significant effects on granule size distribution (GSD). The largest granule mass median diameter was obtained at the lowest rotation speed and highest L/S ratio. The granulation mechanism underlying this continuous process was examined using a wetting and nucleation regime map. For the cases studied here, the mechanical dispersion regime controlled the formation of granule nuclei, leading to a broad GSD and a limited growth ratio.

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Acknowledgements

The authors would like to acknowledge the financial support from National Science Foundation Engineering Research Center on Structured Organic Particulate Systems.

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Authors and Affiliations

  1. Department of Pharmaceutics, Rutgers University, Piscataway, NJ, 08854, USA

    Wei Meng, Thamer Omer & Fernando J. Muzzio

  2. Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08854, USA

    Sarang Oka, Rohit Ramachandran & Fernando J. Muzzio

  3. BASF Corporation, Beachwood, OH, 44122, USA

    Xue Liu

Authors
  1. Wei Meng
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  2. Sarang Oka
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  3. Xue Liu
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Correspondence to Fernando J. Muzzio.

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Meng, W., Oka, S., Liu, X. et al. Effects of Process and Design Parameters on Granule Size Distribution in a Continuous High Shear Granulation Process. J Pharm Innov 12, 283–295 (2017). https://doi.org/10.1007/s12247-017-9288-7

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