The relationship between particulate properties of carrier materials and the adhesion force of drug particles in interactive powder mixtures

Abstract

The influence of particle size, shape, and particle surface roughness of lactose monohydrate carrier particles on the adhesion properties of drug particles in interactive powder mixtures similar in quality of a commercial product (Serevent Diskhaler®) has been investigated. None of the ten lactose monohydrate batches tested was found to be similar in terms of particle size. To obtain more information about particle shape and surface roughness, mathematical analysis was undertaken to structure the data. The lactose monohydrate batches could be split into four different types of particle shape. In terms of particle surface roughness, as measured by a laser profilometer, three different roughness categories were identified. Two sets of mixtures were prepared to relate the physical properties of the lactose monohydrate particles to the adhesion properties of the drug formulations: (a) constant mixing time and speed (25 min, 42 rpm), and (b) optimal mixing time (speed 42 rpm) to match the adhesion properties of the Serevent Diskhaler®. All ten lactose monohydrate batches provided different adhesion properties under test condition (a) and the optimum mixing time [test condition (b)] was also different for each batch. Multivariate data analysis showed that the adhesion force between drug and lactose monohydrate increases with a decrease in particle size and for more irregularly shaped, elongated carrier particles. The effect of surface roughness could only be qualitatively assessed and thus no definitive conclusions can be drawn to judge whether adhesion will increase or decrease as surface roughness changes.