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Investigations into the Formulation of Metered Dose Inhalers of Salmeterol Xinafoate and Fluticasone Propionate Microcrystals

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Abstract

Purpose

To investigate the aerosolization and behaviour of microparticles of salmeterol xinafoate (SX) and fluticasone propionate (FP) suspended in hydrofluoroalkane (HFA) propellant.

Methods

Microcrystals of SX and FP were produced from poly(ethylene glycol) by antisolvent crystallization. The suspension behaviour and aerosolization of the microcrystals when formulated as metered dose inhalers (MDIs) in HFA 134a propellant was compared with that of microparticles produced by micronization (mSX and mFP) using a glass twin stage impinger and by laser light diffraction using a pressurized cell.

Results

FP microparticles underwent non-reversible aggregation in suspension as seen by a doubling in the volume median diameter compared to the raw material. The degree of aggregation of SX particles in suspension was found to decrease as the particle size of the original particles increased. However, because the SX aggregate size was lowest for the particles with the smallest initial size (mSX), the highest fine particle fraction (FPF) of SX was obtained from a suspension of mSX. The FPFs following aerosolization of FP suspensions were similar although the FPF was lowest for particles with the largest original size.

Conclusions

The size of the aggregates in the HFA suspensions was found to correlate directly with the FPFs determined by impaction.

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Acknowledgements

The authors are grateful to MedPharm Ltd. and King’s College London for financial support of this study. We also thank Dr. SA Jones for use of the high pressure circulatory laser diffraction system.

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Authors and Affiliations

  1. King’s College London, Drug Delivery Research Group, Pharmaceutical Science Division, 150 Stamford Street, London, SE1 9NH, UK

    Darragh Murnane, Gary P. Martin & Christopher Marriott

Authors
  1. Darragh Murnane
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  2. Gary P. Martin
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  3. Christopher Marriott
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Corresponding author

Correspondence to Gary P. Martin.

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Murnane, D., Martin, G.P. & Marriott, C. Investigations into the Formulation of Metered Dose Inhalers of Salmeterol Xinafoate and Fluticasone Propionate Microcrystals. Pharm Res 25, 2283–2291 (2008). https://doi.org/10.1007/s11095-008-9622-3

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  • DOI: https://doi.org/10.1007/s11095-008-9622-3

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