The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations I: Direct Quantification by Atomic Force Microscopy

Abstract

To obtain a quantitative assessment of the cohesive and adhesive force balance within dry powder inhaler formulations. The atomic force microscope (AFM) colloid probe technique was used to measure the adhesive and cohesive force characteristics of dry powder systems containing an active component (budesonide, salbutamol sulphate) and alpha-lactose monohydrate. To minimize the variations in contact area between colloid probe and substrates, nanometer smooth crystal surfaces of the drugs and the excipient were prepared. The uniformity in contact area allowed accurate and reproducible force measurements. Cohesive-adhesive balance (CAB) graphs were developed to allow direct comparison of the interaction forces occurring in model carrier-based formulations. A salbutamol sulphate-lactose system revealed a significant tendency for the two materials to adhere, suggesting a propensity for the powder to form a homogenous blend. In contrast, the budesonide-lactose system exhibited strong cohesive properties suggesting that the formulation may exhibit poor blend homogeneity and potential for segregation upon processing and handling. The novel approach provides a fundamental insight into the cohesive-adhesive balances in dry powder formulations and further understanding of powder behavior.