Dissolution of crystalline and amorphous particles in the aerosol phase



Dissolution Of Crystalline And Amorphous Particles In The Aerosol Phase

Natalie Armstrong Green1, Allen Haddrell1, Jonathan Reid1, David Lewis2 & Tanya Church2

1School of Chemistry, University of Bristol, Bristol, BS81TS, United Kingdom

2Chiesi Limited, Bath Road Industrial Estate, Chippenham, Wilts, United Kingdom


Dry powder inhalers have become a popular inhalation delivery system due to good drug stability and a minimal need for patient coordination.[1] The powdered mixture consists of large, course carrier particles, e.g. lactose, and an active pharmaceutical ingredient (API), e.g. salbutamol sulphate. Given that the efficacy of the drug is dependent on where the dose is delivered, it is important to understand the physicochemical properties of the aerosol to predict dose. Once inhaled, the dry particles experience a warm humid environment where, depending on their solubility properties, they can take up water. A particle that fully dissolves in the aerosol phase will grow during inhalation, the magnitude of growth is controlled by its hygroscopicity. This dynamic size change influences the deposition mechanism, thus the deposited fraction. A particle that partially dissolves or remains solid, will experience a different deposition pattern, and deposit on the lung surface in a different physical state. Here, we report for the first time, dissolution measurements in the aerosol phase of a pharmaceutical aerosol comprising: sodium chloride and salbutamol sulphate. An adapted comparative kinetics electrodynamic balance (CK-EDB) has been used to replicate the dissolution process of dry powder particles in the aerosol phase experienced in the lung. The CK-EDB traps individual particles within its core and monitors size/phase change as a function of time (0.01 second resolution) and environmental conditions (relative humidity and temperature which can be changed <0.1 seconds).