Prediction of the particle size distribution of the aerosol generated by a pressurized metered-dose inhaler

• Published in: Powder technology Vol. 399; p. 117151
• Main Authors: de Charras, Yamila L., Ramírez-Rigo, M. Verónica, Bertin, Diego E.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01-02-2022; Elsevier BV
• Subjects: Aerosol technology; Aerosols; Atomizing; Drug delivery; Drug dosages; Entropy; Flow stability; Inhalers; Mathematical model; Mathematical models; Maximum entropy; Particle size; Particle size distribution; Respiratory drug delivery; Respiratory tract; Salbutamol; Size distribution; Particle size distribution; Aerosol technology; Mathematical model; Respiratory drug delivery
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2022.117151

Pressurized metered dose inhalers (pMDIs) are devices widely used for drug delivery in the respiratory tract. In this work, a mathematical model to predict the complete particle size distribution (PSD) of the aerosol generated by a pMDI is developed. The model combines the equations developed by Clark in 1999 that describe the flow within the inhaler, the Linear Instability Sheet Atomization (LISA) model and a method based on the Maximum Entropy Principle (MEP). Mathematically it is found that the PSD can be represented by a lognormal function with geometric standard deviation equal to 1.56. The model does not contain fitting parameters and is validated with experimental information for a formulation containing salbutamol and HFA-134a as drug and propellant, respectively. Simulations are performed to explore how the propellants HFA-134a and HFA-227ea affect the PSD of the aerosol generated by the inhaler.
Comparison of the predicted and experimental PSDs. [Display omitted]
•A model to predict the particle size distribution generated by a pMDI is developed.•The PSD is well described by a lognormal function with a geometric standard constant.•The model allows to analyze how the formulation properties impact the aerosol size.