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Critical Solvent Properties Affecting the Particle Formation Process and Characteristics of Celecoxib-Loaded PLGA Microparticles via Spray-Drying

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ABSTRACT

Purpose

It is imperative to understand the particle formation mechanisms when designing advanced nano/microparticulate drug delivery systems. We investigated how the solvent power and volatility influence the texture and surface chemistry of celecoxib-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles prepared by spray-drying.

Methods

Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA).

Results

Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures.

Conclusions

The particle formation process is mainly governed by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition.

 

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was funded by The Danish Council for Technology and Innovation via the Innovation Consortium NanoMorph (952320/2009), The Drug Research Academy and The Danish Agency for Science, Technology and Innovation. The authors would also like to thank Erik Wisaeus, Kenneth Brian Haugshøj and Pia Wahlberg (Danish Technological Institute) and Dorthe Ørbæk (Faculty of Health and Medical Sciences, University of Copenhagen) for technical assistance with the SEM, FIB-SEM, XPS and TGA analysis.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen Ø, Denmark

    Feng Wan, Adam Bohr, Camilla Foged, Jukka Rantanen & Mingshi Yang

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

    Adam Bohr

  3. Biopharma Application Development, Novozymes Biopharma A/S, Krogshoejvej 36, 2880, Bagsvaerd, Denmark

    Morten Jonas Maltesen

  4. Preformulation and Delivery/Oral Protein Delivery Diabetes Research Unit, Novo Nordisk A/S, Måløv Byvej 200, 2760, Måløv, Denmark

    Simon Bjerregaard

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  1. Feng Wan
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  2. Adam Bohr
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Correspondence to Mingshi Yang.

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Feng Wan and Adam Bohr contributed equally to the manuscript.

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Wan, F., Bohr, A., Maltesen, M.J. et al. Critical Solvent Properties Affecting the Particle Formation Process and Characteristics of Celecoxib-Loaded PLGA Microparticles via Spray-Drying. Pharm Res 30, 1065–1076 (2013). https://doi.org/10.1007/s11095-012-0943-x

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  • DOI: https://doi.org/10.1007/s11095-012-0943-x

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