Dissolution Techniques for In Vitro Testing of Dry Powders for Inhalation
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To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders.
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.
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.
The paddle apparatus with membrane holder has the best discrimination power with optimal reproducibility.
KEY WORDSdiffusion flow through cell Franz diffusion cell paddle apparatus aerosol for inhalation
Andersen cascade impactor
dry powder inhaler
high performance liquid chromatography
mean dissolution time
scanning electron microscopy
simulated lung fluid
ACKNOWLEDGMENTS & DISCLOSURES
Wolfgang Bootz (Boehringer Ingelheim) and Dr. Bernhard Meier for SEM pictures
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