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Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation

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ABSTRACT

Purpose

To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders.

Methods

From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerated cellulose membranes using an abbreviated Andersen cascade impactor. The membrane was then transferred to the respective dissolution set up either paddle apparatus with membrane holder, flow through cell or Franz diffusion cell.

Results

All tested dissolution techniques could discriminate between good and poorly soluble substances, but only the paddle apparatus differentiated between small variations of solubility. We showed that membrane coverage and particle diameter play an important role for the dissolution rate. The profiles were fitted with mathematical models (e.g., Weibull, first order) choosing the best fit for determination of the mean dissolution time. Furthermore, a correlation between the dissolution profiles obtained with Franz cell compared to paddle apparatus could be shown.

Conclusion

The paddle apparatus with membrane holder has the best discrimination power with optimal reproducibility.

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Abbreviations

ACI:

Andersen cascade impactor

DPI:

dry powder inhaler

HPLC:

high performance liquid chromatography

MDT:

mean dissolution time

PE:

polyethylen

PEEK:

polyetherketone

RC:

regenerated cellulose

SEM:

scanning electron microscopy

SLF:

simulated lung fluid

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ACKNOWLEDGMENTS & DISCLOSURES

Wolfgang Bootz (Boehringer Ingelheim) and Dr. Bernhard Meier for SEM pictures

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Authors and Affiliations

  1. PharmBioTec GmbH, Saarbrücken, Germany

    Sabine May, Marc Schneider & Claus Michael Lehr

  2. Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany

    Birte Jensen & Markus Wolkenhauer

  3. Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany

    Marc Schneider & Claus Michael Lehr

  4. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarbrücken, Germany

    Claus Michael Lehr

Authors
  1. Sabine May
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  2. Birte Jensen
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  3. Markus Wolkenhauer
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  4. Marc Schneider
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  5. Claus Michael Lehr
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Corresponding author

Correspondence to Marc Schneider.

Electronic supplementary material

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Figure S1

DSC of substance A amorphous base: glass transition point is between 6 and 10 minutes at approx. 110 °C (heating rate 10 °C/min) (DOCX 396 kb)

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May, S., Jensen, B., Wolkenhauer, M. et al. Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation. Pharm Res 29, 2157–2166 (2012). https://doi.org/10.1007/s11095-012-0744-2

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  • DOI: https://doi.org/10.1007/s11095-012-0744-2

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