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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.

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

Drug development and industrial pharmacy (2013-11-21)
T Ehtezazi, M J Davies, L Seton, M N Morgan, S Ross, G D Martin, I M Hutchings
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Albuterol sulfate, Pharmaceutical Secondary Standard; Certified Reference Material
Salbutamol sulfate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
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Glycerol solution, puriss., meets analytical specification of Ph. Eur., BP, 84-88%
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Glycerol, tested according to Ph. Eur., anhydrous
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Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
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Glycerol, FCC, FG
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Glycerin, meets USP testing specifications
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Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
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Glycerol, for molecular biology, ≥99.0%
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Salbutamol hemisulfate salt, ≥98%
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Glycerol, BioXtra, ≥99% (GC)
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Glycerol, ≥99.5%
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Glycerol, SAJ first grade, ≥98.0%
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Glycerol, JIS special grade, ≥99.0%
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Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material
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Glycerol, puriss., anhydrous, 99.0-101.0% (alkalimetric)
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Glycerol, puriss. p.a., ACS reagent, anhydrous, dist., ≥99.5% (GC)
USP
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Glycerol, analytical standard