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Pharmaceutical Research

, Volume 29, Issue 8, pp 2157–2166 | Cite as

Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation

  • Sabine May
  • Birte Jensen
  • Markus Wolkenhauer
  • Marc Schneider
  • Claus Michael Lehr
Research Paper

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.

KEY WORDS

diffusion flow through cell Franz diffusion cell paddle apparatus aerosol for inhalation 

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

Notes

ACKNOWLEDGMENTS & DISCLOSURES

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

Supplementary material

11095_2012_744_MOESM1_ESM.docx (397 kb)
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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sabine May
    • 1
  • Birte Jensen
    • 2
  • Markus Wolkenhauer
    • 2
  • Marc Schneider
    • 1
    • 3
  • Claus Michael Lehr
    • 1
    • 3
    • 4
  1. 1.PharmBioTec GmbHSaarbrückenGermany
  2. 2.Boehringer Ingelheim Pharma GmbH & Co KGIngelheimGermany
  3. 3.Biopharmaceutics and Pharmaceutical TechnologySaarland UniversitySaarbrückenGermany
  4. 4.Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)Helmholtz Center for Infection Research (HZI)SaarbrückenGermany

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