Effect of mixing time and mixing rate on the evolution of powderproperties for binary adhesive mixtures

Abstract: Dry powder inhalers (DPIs) are often used to deliver drugs to the lungs when treating respiratory diseases. Inhalation powders are often formulated as adhesive mixtures which is the main formulation type used for dry inhalation powders of pharmaceuticals. The fine particulate active pharmaceutical ingredient (API) of interest is mixed with a coarser carrier resulting in an adhesion of the API on to the surface of the larger sized carrier. The aim of this project was to investigate how mixing time and mixing rate influences the morphology and bulk properties of mixtures with different surface to coverage ratios (SCRs). Several analyses of bulk properties were made and a sieve analysis was also conducted to obtain information of the stability of randomly chosen samples. The results showed that mixing time and mixing rate influence the morphology and bulk properties of the adhesive mixtures in different ways. The bulk density and permeability decreased with higher SCR. The bulk density did not seem to be highly affected by mixing time or rate, while the permeability decreased with an increasing mixing rate (i.e. when increasing from 22 to 67 rpm). Regarding the Hausner ratio and compressibility, an increase in SCR increased the HR (with subsequent increase in compressibility). Comparing mixing rates 22 and 67 rpm, an increasing mixing rate appeared to produce mixtures which showed a more stable pattern over mixing time, i.e. less variation in values, in mixtures of SCR 0.5 and 2, while in mixtures of SCR 1, values appeared to fluctuate more. When analyzing the microscopy images, it was observed that SCR 1 with the mixing rate 22 rpm had the smallest agglomerates of all mixture times (when comparing with SCR 0.5 and SCR 2). The mixtures with the highest w/w% of agglomerates above 500 μm were of SCR 2 at both mixing rates and at all mixing times. These mixtures had lower permeability values which is understandable, as it is more difficult for air to get through the powder with large amount of agglomerates in the way. The w/w % for the particles between 90 μm < d < 500 μm was very close for SCR 0.5 and SCR 1. The patterns of the results from the conducted methods appears to be more alike for SCR 0.5 and 1, whereas SCR 2 is more deviant throughout the project.