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The Effects of Excipients and Particle Engineering on the Biophysical Stability and Aerosol Performance of Parathyroid Hormone (1-34) Prepared as a Dry Powder for Inhalation

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Abstract

Pulmonary delivery of therapeutic peptides and proteins has many advantages including high relative bioavailability, rapid systemic absorption and onset of action and a non-invasive mode of administration which improves patient compliance. In this study, we investigated the effect of spray-drying (SD) and spray freeze-drying processes on the stability and aerosol performance of parathyroid hormone (PTH) (1-34) microparticles. In this study, the stabilisation effect of trehalose (a non-reducing sugar) and Brij 97 (a non-ionic surfactant) on spray-dried PTH particles was assessed using analytical techniques including circular dichroism (CD), fluorescence spectroscopy, modulated differential scanning calorimetry and an in vitro bioactivity assay. Physical characterisation also included electron microscopy, tap density measurement and laser light diffraction. The aerosol aerodynamic performance of the formulations was assessed using the Andersen cascade impactor. Based on these studies, a formulation for spray freeze-drying was selected and the effects of the two particle engineering techniques on the biophysical stability and aerosol performance of the resulting powders was determined. CD, fluorescence spectroscopy and bioactivity data suggest that trehalose when used alone as a stabilising excipient produces a superior stabilising effect than when used in combination with a non-ionic surfactant. This highlights the utility of CD and fluorescence spectroscopy studies for the prediction of protein bioactivity post-processing. Therefore, a method and formulation suitable for the preparation of PTH as a dry powder was developed based on spray-drying PTH with trehalose as a stabiliser with the bioactivity of SD PTH containing trehalose being equivalent to that of unprocessed PTH.

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Acknowledgements

This research was supported by Science Foundation Ireland under grants SFI RFPENG0020 & SFI07/SRC/B1154.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Thomas Jefferson University, Edison Building, 130 South 9th Street, Philadelphia, Pennsylvania, 19107-5233, USA

    Sunday A. Shoyele

  2. Freund Pharmatec Ltd, Unit 1, IDA Business & Technology Park, Tullamore, Co.Offaly, Ireland

    Neeraj Sivadas

  3. School of Pharmacy, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland

    Sally-Ann Cryan

Authors
  1. Sunday A. Shoyele
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  2. Neeraj Sivadas
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  3. Sally-Ann Cryan
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Correspondence to Sally-Ann Cryan.

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Shoyele, S.A., Sivadas, N. & Cryan, SA. The Effects of Excipients and Particle Engineering on the Biophysical Stability and Aerosol Performance of Parathyroid Hormone (1-34) Prepared as a Dry Powder for Inhalation. AAPS PharmSciTech 12, 304–311 (2011). https://doi.org/10.1208/s12249-011-9585-2

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  • DOI: https://doi.org/10.1208/s12249-011-9585-2

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