Mixing has always been overlooked in the production of dry powder inhaler (DPI) formulations. This study radically investigates the effect of mixing energy on the behaviour of drug-carrier interactions in single active DPI formulations as a function of three different carrier particle sizes (63-90 µm, 125-180 µm and 210-250 µm). Binary mixtures containing coarse lactose (CL) and the active drug, Salbutamol Sulphate (SS) were prepared in triplicates and mixed in eight different mixer rotations and each of these batches were tested for blend homogeneity by using the percentage of relative standard deviation (%RSD) of the drug concentration in six samples. When mixing energy was increased, there was an astonishing and surprising non-linear but similar trends in blend homogeneity observed for all three formulations. This can be divided into four distinct stages in which, during the initial mixing process, there was a non-homogeneous stage, followed by a homogeneous stage at around 13000 mixer rotations and a variable region, where there is a sudden decrease in homogeneity before it reaches a constant homogenous stage at very high mixer rotations (~40000 mixer rotations). Hence, a significant mechanism depicting the interparticulate interactions occurring during the mixing process was proposed in this study. The results obtained by this study ratifies that mixing energy does affect DPI formulation performance and the particle size of carrier employed in the formulation was shown to affect the interparticulate interactions occurring between the drug-carrier and mixing can potentially be utilized to evaluate these interactions.
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