Influence of the blending process on the quality and physicochemical properties of inhalation powders

Abstract

With increasing understanding of the lung physiology and respiratory diseases, drugs delivered directly to the lungs are becoming an alternative choice to treat local and systemic diseases. Currently, the most common inhalation products are inhalation powders administered with the use of the dry powder inhalers (DPI), in which the aerosolization of solid particles in the air is activated by the intensive inhalation performed by the patient. Only micronized drug substances with suitable aerodynamic size (1-5 µm) can efficiently reach the lungs and be deposited there. The particle size is not the only parameter determining the required aerodynamic properties of the powder. Appropriate lung deposition is also achieved by using a suitable carrier with larger particles, most often lactose. The selection of a carrier with appropriate properties and its proper introduction into the mixture is extremely important for its interactions with drug substance and for obtaining the appropriate fine particle dose. For the quality of the medicinal product, the mixing step of ingredients in inhalation powder is a critical step that requires to be optimized and controlled. The parameters of the mixing process must be selected so that the interparticulate adhesion forces between the particles of the carrier and the drug substance (van der Waals forces, electrostatic interactions, capillary phenomena and mechanical adjustment) are strong enough to achieve homogeneity and stability of the mixture during the use and at the same time, allowing for easy separation into its primary components upon aerosolisations. The aim of this work is to describe the physicochemical and technological factors influencing the quality of powder mixtures intended for inhalation. Among the characteristic features of the carrier, the most important are particle size and shape, density, polymorphism and surface properties that can be modified. The importance of the order in which the ingredients are added during mixing is emphasized, as well as type of mixer, mixing speed and batch size. In addition to the aerodynamic properties of obtained powder, mechanical properties (flowability) must be controlled. Microscopic and spectroscopic methods allow to observe the interactions between the particles of ingredients, during the product development phase or in process control.

Keywords

• manufacturing
• inhalation powders
• dpi
• blending process
• interparticulate forces