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.

Disorder and twinning in molecular crystals: impurity-induced effects in adipic acid.

The variation in physical properties of crystals grown in the presence of additives or impurities have previously been attributed to lattice disorder developed during crystallization. Adipic acid crystallized in the presence of a variety of stereochemically related impurities typifies such behavior with disorder manifest in variations of dissolution rates and enthalpies of solution and fusion. In this case the most extreme habit, produced by the presence of added monoalkanoic acids, is a rounded dumbbell that was suggested previously to be a twinned crystal. In this contribution such crystals are fully characterized both through their external morphology and by means of single crystal X-ray diffraction. These techniques show that these particles are not twinned but rather are disordered single crystals comprising a small number of slightly misaligned domains. The interaction between additive and substrate is modeled and new additives selected that induce the formation of true mechanical twins in adipic acid.