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Physicochemical Characterization and Water Vapor Sorption of Organic Solution Advanced Spray-Dried Inhalable Trehalose Microparticles and Nanoparticles for Targeted Dry Powder Pulmonary Inhalation Delivery

  • Research Article
  • Theme: Advances in Pharmaceutical Excipients Research and Use: Novel Materials, Functionalities and Testing
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Abstract

Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T g). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C.

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ACKNOWLEDGEMENTS

The authors gratefully acknowledge financial support from the UK Daniel P. Reedy Fellowship and Fellowship support from the UK Center of Membrane Sciences awarded to Xiaojian Li. The authors thank Dr. Dicky Sick Ki Yu for SEM access and Dr. Tonglei Li for XRPD and HSM access.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences—Drug Development Division, University of Kentucky College of Pharmacy, 789 S. Limestone Street, Lexington, Kentucky, 40536-0596, USA

    Xiaojian Li & Heidi M. Mansour

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  1. Xiaojian Li
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  2. Heidi M. Mansour
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Correspondence to Heidi M. Mansour.

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Guest Editors: Otilia Koo, Thomas Farrell, Allison Radwick, and Sameer Late

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Li, X., Mansour, H.M. Physicochemical Characterization and Water Vapor Sorption of Organic Solution Advanced Spray-Dried Inhalable Trehalose Microparticles and Nanoparticles for Targeted Dry Powder Pulmonary Inhalation Delivery. AAPS PharmSciTech 12, 1420–1430 (2011). https://doi.org/10.1208/s12249-011-9704-0

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  • DOI: https://doi.org/10.1208/s12249-011-9704-0

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