Pharmaceutical Research

, Volume 31, Issue 11, pp 3211–3224 | Cite as

Dissolution Testing of Powders for Inhalation: Influence of Particle Deposition and Modeling of Dissolution Profiles

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



The aim of this study was to investigate influencing factors on the dissolution test for powders for pulmonary delivery with USP apparatus 2 (paddle apparatus).


We investigated the influence of dose collection method, membrane holder type and the presence of surfactants on the dissolution process. Furthermore, we modeled the in vitro dissolution process to identify influencing factors on the dissolution process of inhaled formulations based on the Nernst-Brunner equation.


A homogenous distribution of the powder was required to eliminate mass dependent dissolution profiles. This was also found by modeling the dissolution process under ideal conditions. Additionally, it could be shown that influence on the diffusion pathway depends on the solubility of the substance.


We demonstrated that the use of 0.02% DPPC in the dissolution media results in the most discriminating and reproducible dissolution profiles.

In the model section we demonstrated that the dissolution process depends strongly on saturation solubility and particle size. Under defined assumptions we were able show that the model is predicting the experimental dissolution profiles.


aerodynamic diameter (MMAD) Andersen cascade impactor Nernst Brunner equation paddle apparatus 



Abbreviated Andersen cascade impactor


Andersen cascade impactor




Active pharmaceutical ingredient




European Medicines Agency


Food and Drug Administration


Fine particle dose


High performance liquid chromatography


Abbreviated Andersen cascade impactor with stage extension and modified filter stage


Phosphate buffered saline


Regenerated cellulose membrane


Reversed phase


Sodium dodecyl sulfate


Stage extension


Scanning electron microscopy


United States Pharmacopoeia





Dynamic viscosity of water at 37°C


Solubility of drug


Concentration of the drug in the solution at time t


Diffusion coefficient of substance in the solvent


Aerodynamic particle diameter


Geometric particle diameter


Mass of solid material at time t


Time interval


Difference factor


Similarity factor


Diffusion (boundary) layer thickness


Shape factor


Amount of drug released


Number of particles in a particle size fraction




Mean percent drug released at each time point for reference product


The surface area of the particles


The surface area of each particle size fraction




Mean percent drug released at each time point for test product




Van der Waals volume

Xe (0)

The amount of undissolved drug in a particle size group


The amount of undissolved drug in a particle size group e


Total amount of undissolved drug at time t



Thanks to Dr. Holger Wagner, Dr. Peter Häbel and team (Boehringer Ingelheim) for calculating the van der Waals volumes of the substances and to Wolfgang Bootz (Boehringer Ingelheim) and Dr. Bernhard Meier for the SEM pictures.

Supplementary material

11095_2014_1413_MOESM1_ESM.docx (65 kb)
Fig. S1 (DOCX 64 kb)
11095_2014_1413_MOESM2_ESM.docx (16 kb)
Table S1 (DOCX 15 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sabine May
    • 1
    • 2
  • Birte Jensen
    • 2
  • Claudius Weiler
    • 2
  • Markus Wolkenhauer
    • 2
  • Marc Schneider
    • 1
    • 3
  • Claus-Michael Lehr
    • 1
    • 4
    • 5
  1. 1.PharmBioTec GmbHSaarbrückenGermany
  2. 2.Boehringer Ingelheim Pharma GmbH & Co KGIngelheimGermany
  3. 3.Pharmaceutics and BiopharmacyPhilipps-Universität MarburgMarburgGermany
  4. 4.Biopharmaceutics and Pharmaceutical TechnologySaarland UniversitySaarbrückenGermany
  5. 5.Helmholtz Institute for Pharmaceutical Sciences SaarlandHelmholtz Center for Infection ResearchSaarbrückenGermany

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