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Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs.

Ehtezazi, T and Davies, MJ and Seton, L and Morgan, MN and Ross, S and Martin, GD and Hutchings, IM (2015) Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs. Drug Dev Ind Pharm, 41. pp. 279-291.

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Abstract

Conventional suspension pressurized metered dose inhalers (pMDIs) suffer not only from delivering small amounts of a drug to the lungs, but also the inhaled dose scatters all over the lung regions. This results in much less of the desired dose being delivered to regions of the lungs. This study aimed to improve the aerosol performance of suspension pMDIs by producing primary particles with narrow size distributions. Inkjet spray drying was used to produce respirable particles of salbutamol sulfate. The Next Generation Impactor (NGI) was used to determine the aerosol particle size distribution and fine particle fraction (FPF). Furthermore, oropharyngeal models were used with the NGI to compare the aerosol performances of a pMDI with monodisperse primary particles and a conventional pMDI. Monodisperse primary particles in pMDIs showed significantly narrower aerosol particle size distributions than pMDIs containing polydisperse primary particles. Monodisperse pMDIs showed aerosol deposition on a single stage of the NGI as high as 41.75 ± 5.76%, while this was 29.37 ± 6.79% for a polydisperse pMDI. Narrow size distribution was crucial to achieve a high FPF (49.31 ± 8.16%) for primary particles greater than 2 µm. Only small polydisperse primary particles with sizes such as 0.65 ± 0.28 µm achieved a high FPF with (68.94 ± 6.22%) or without (53.95 ± 4.59%) a spacer. Oropharyngeal models also indicated a narrower aerosol particle size distribution for a pMDI containing monodisperse primary particles compared to a conventional pMDI. It is concluded that, pMDIs formulated with monodisperse primary particles show higher FPFs that may target desired regions of the lungs more effectively than polydisperse pMDIs.

Item Type: Article
Uncontrolled Keywords: Inkjet monodisperse particles oropharyngeal models pressurized metered dose inhalers spray drying Administration, Inhalation Aerosols Albuterol Bronchodilator Agents Chemistry, Pharmaceutical Drug Delivery Systems Drug Stability Humans Lung Metered Dose Inhalers Microscopy, Electron, Scanning Models, Biological Particle Size
Subjects: UNSPECIFIED
Divisions: Div E > Production Processes
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 19:09
Last Modified: 14 Sep 2017 01:27
DOI: