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Scaling Up the Spray Drying Process from Pilot to Production Scale Using an Atomized Droplet Size Criterion

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Abstract

Purpose

The purpose of this study was to investigate the possibility of producing identical powders in pilot and production scale spray drying equipment by matching the droplet size distributions produced by two differently sized atomizers.

Methods

Particles were prepared by spray drying solutions of acetaminophen and polyvinylpyrrolidone K-30. The success of the up-scaling was evaluated by comparing the powders in terms of particle size distribution (laser diffraction), crystallinity (XPRD) and morphology (SEM). Furthermore, the influence of process parameters on other product characteristics such as stability and residual volatile content was also evaluated.

Results

The spray drying experiments resulted in spherical, amorphous particles with volumetric median diameters of typically 4–10 μm for pilot scale and 4–30 μm for production scale. The results showed that particles with similar morphology and crystallinity could be produced in the two applied spray dryers. However, scale-up based purely on matching droplet size distributions was not feasible.

Conclusions

The scale-up criterion did not account for the differences between the droplet-drying gas mixing and residence time distribution within the two spray dryers. Therefore, production scale experiments are required in order to obtain similar product characteristics as in pilot scale.

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Acknowledgments

The Drug Research Academy, GEA Pharmaceutical A/S, and Niro A/S are acknowledged for financial support. The authors would like to thank Matti Murtomaa and University of Turku for use of X-ray diffractometer and microcalorimeter. Mikko Tenho and Olli-Pekka Hämäläinen are greatly appreciated for their assistance in XRPD and isothermal microcalorimetry measurements.

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Author notes

  1. Sune Klint Andersen

    Present address: Novo Nordisk A/S, Novo Nordisk Park, 2760, Maaloev, Denmark

Authors and Affiliations

  1. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Pia Thybo & Lars Hovgaard

  2. Niro A/S, Gladsaxevej 305, 2860, Soeborg, Denmark

    Jesper Sæderup Lindeløv, Anders Brask & Sune Klint Andersen

  3. Novo Nordisk A/S, Novo Nordisk Park, 2760, Maaloev, Denmark

    Lars Hovgaard

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  1. Pia Thybo
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Correspondence to Pia Thybo.

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Thybo, P., Hovgaard, L., Lindeløv, J.S. et al. Scaling Up the Spray Drying Process from Pilot to Production Scale Using an Atomized Droplet Size Criterion. Pharm Res 25, 1610–1620 (2008). https://doi.org/10.1007/s11095-008-9565-8

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  • DOI: https://doi.org/10.1007/s11095-008-9565-8

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