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

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.

Virus infections and acute renal transplant rejection.

The date of onset of 360 acute renal transplant rejection episodes from 1969 to 1973 have been compared with the prevalence of various common viral infections and infections due to Mycoplasma pnuemoniae. A positive correlation was found for influenza B infections (r=0.43, p less than 0.01) up to 5 months before transplantation and for adenovirus infections (r=0.32, p less than 0.05) at 1 month before kidney grafting.