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Published on: April 6, 2017
In vitro/in vivo comparisons in pulmonary drug delivery
Stephen P Newman1, Hak-Kim Chan
1steve.newman@physics.org
Summary
In vitro aerodynamic particle size distribution (APSD) data can predict lung deposition for inhaled drugs. Lung deposition closely matches the aerosol dose smaller than 3 micrometers, improving inhaler device comparisons.
Area of Science:
- Pharmaceutical Sciences
- Respiratory Drug Delivery
- Inhalation Technology
Background:
- Establishing in vitro-in vivo correlations for inhaled drugs is crucial for product development.
- Aerodynamic particle size distribution (APSD) is a key in vitro metric for predicting lung deposition and clinical effects.
- Current methods for measuring APSD may not fully represent the in vivo conditions of drug delivery.
Purpose of the Study:
- To investigate the relationship between in vitro APSD and in vivo lung deposition for inhaled drug products.
- To evaluate the predictive power of different APSD metrics for lung deposition across various inhaler devices.
- To identify potential improvements in in vitro methods for better correlation with clinical outcomes.
Main Methods:
- Comparison of APSD data from cascade impaction with lung deposition data from gamma scintigraphy studies.
- Analysis of whole-lung deposition in relation to fine particle fraction (FPF) and particle size distributions.
- Evaluation of different FPF definitions (e.g., <5.8 µm, <6.8 µm) and their correlation with deposition.
Main Results:
- Whole-lung deposition showed a significant correlation with FPF across different inhaler devices.
- FPF metrics systematically overestimated lung deposition for most inhalers.
- Lung deposition demonstrated closer numerical equivalence to the percentage of aerosol dose <3 µm.
Conclusions:
- Correlations between APSD and whole-lung deposition support the use of APSD for comparing inhaler devices.
- Measuring APSD using methods that mimic clinical use, such as simulated upper airway anatomy, may improve in vitro-in vivo agreement.
- Further research is needed to establish unambiguous links between APSD and clinical response for inhaled drugs.
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