Segregation in inhalable powders: Quantification of the effect of vibration on adhesive mixtures

The objective of this investigation was to study the effect of induced vibrations on adhesive mixtures containing budesonide and salbutamol sulphate as active pharmaceutical ingredients (APIs) and InhaLac 70 as carrier. A series of adhesive mixtures with varied API concentration (1-4%) was prepared for each API. Half of the adhesive mixture was stressed on a vibrating sieve under conditions resembling hopper flow. Based on scanning electron micrographs, it was concluded that InhaLac 70 contains particles of two distinct shapes, one irregular with groves and valleys and the other more regular with well defined edges. The dispersibility of the control and stressed mixtures was studied using a next generation impactor. The stressed mixtures containing 1 and 1.5% API displayed a significant reduction in fine particle dose (FPD) compared to the control. The reduction in FPD resulted from a loss of API from the adhesive mixture during vibration and as a consequence of restructuring and self agglomeration resulting in reduced dispersibility. However, no significant difference was observed for mixtures with larger weight fractions of API (2 and 4% API) but these have a drawback of reduced fine particle fraction (FPF). It is concluded that vibrations induced on the adhesive mixtures during handling potentially have a significant effect on the dispersibility of the API and the total amount of drug delivered to the lungs.