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Pharmaceutical microparticle engineering with electrospraying: the role of mixed solvent systems in particle formation and characteristics

  • Engineering and Nano-engineering Approaches for Medical Devices
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Abstract

Microparticles of Celecoxib, dispersed in a matrix of poly(lactic-co-glycolic acid) (PLGA), were prepared by electrospraying using different solvent mixtures to investigate the influence upon particle formation and the resulting particle characteristics. Mixtures consisting of a good solvent, acetone, and an anti-solvent, methanol, for PLGA were studied in different ratios. Properties of the spraying solutions were examined and the resulting microparticles were characterized with regard to size, morphology, porosity, solid state form, surface chemistry and drug release. Particle formation was strongly influenced by the polymer molecular conformation during droplet formation and by the anti-solvent concentration during droplet drying. A strong correlation was found between particle morphology and the solubility of the polymer in the solvent mixtures. The lack of chain entanglements in droplets containing anti-solvent resulted in compact polymer conformation and grain-like particle morphology. Further, the early precipitation of polymer and low chain interaction with increasing content of anti-solvent resulted in surface enrichment of drug (from 10 and 20 % up to 41 and 57 % respectively), also demonstrated by the increasingly higher drug release rates. The results demonstrate the importance of solvent composition in particle preparation and indicate potential for exploiting this dependence to improve pharmaceutical particle design and performance.

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Acknowledgments

The Authors would like to thank the Danish Agency for Science, Technology and Innovation and Veloxis Pharmaceuticals A/S for financial support of this project.

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Authors and Affiliations

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

    Adam Bohr, Feng Wan, Stefania Baldursdottír & Mingshi Yang

  2. Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK

    Adam Bohr, Eleanor Stride & Mohan Edirisinghe

  3. Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, 2300, Copenhagen, Denmark

    Jakob Kristensen

  4. Iota NanoSolutions Ltd, MerseyBio, Crown Street, Liverpool, L69 7ZB, UK

    Mark Dyas

  5. Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Headington, OX3 7DQ, UK

    Eleanor Stride

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  1. Adam Bohr
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  2. Feng Wan
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  3. Jakob Kristensen
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  4. Mark Dyas
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  7. Mohan Edirisinghe
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  8. Mingshi Yang
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Correspondence to Adam Bohr.

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Bohr, A., Wan, F., Kristensen, J. et al. Pharmaceutical microparticle engineering with electrospraying: the role of mixed solvent systems in particle formation and characteristics. J Mater Sci: Mater Med 26, 61 (2015). https://doi.org/10.1007/s10856-015-5379-5

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  • DOI: https://doi.org/10.1007/s10856-015-5379-5

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