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Raman Map** of Mannitol/Lysozyme Particles Produced Via Spray Drying and Single Droplet Drying

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ABSTRACT

Purpose

This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations.

Methods

A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data.

Results

XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman map** indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles.

Conclusions

It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.

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ACKNOWLEDGMENTS AND DISCLOSURES

Funding from The Danish Council for Technology and Innovation for the Innovation Consortium NanoMorph (952320/2009) is acknowledged. Erik Wisaeus (Danish Technology Institute) is acknowledged for his wonderful work on SEM. The grant from Lundbeckfonden for the purchase of X-ray powder diffractometer is acknowledged (grant decision 479/06). Erik Skibsted from Novo Nordisk A/S is acknowledged for his enthusiastic support with Raman map** technique.

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Authors and Affiliations

  1. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Jari Pekka Pajander, Sanni Matero, Feng Wan, Jukka Rantanen & Mingshi Yang

  2. Quality and Technology, Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg, Denmark

    Sanni Matero

  3. GEA Process Engineering A/S, Gladsaxevej 305, 2860, Soeborg, Denmark

    Jakob Sloth

Authors
  1. Jari Pekka Pajander
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  2. Sanni Matero
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  4. Feng Wan
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  5. Jukka Rantanen
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  6. Mingshi Yang
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Correspondence to Mingshi Yang.

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Pajander, J.P., Matero, S., Sloth, J. et al. Raman Map** of Mannitol/Lysozyme Particles Produced Via Spray Drying and Single Droplet Drying. Pharm Res 32, 1993–2002 (2015). https://doi.org/10.1007/s11095-014-1592-z

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  • DOI: https://doi.org/10.1007/s11095-014-1592-z

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