The development of a cascade impactor simulator based on adhesion force measurements to aid the development of dry...

Adhesion and friction forces are the main physical factors determining the re-suspension of a micronized drug from carrier particles during inhalation. Hence, it appears useful to link adhesion and friction force measurements to the in vitro testing of dry powder inhalations, namely the assessment of the mass median aerodynamic diameter (MMAD) using an eight-stage Andersen cascade impactor. Interactive mixtures of micronized Salmeterol Xinafoate adhered to irrespirable lactose monohydrate carrier particles were used as model dosage forms. The adhesion force between the drug and carrier particles was assessed using a centrifuge technique, and the MMAD was determined under standardized working conditions using the Andersen-Cascade impactor (Mark II). A cascade impactor simulator (CIS), which is a computer program containing a re-suspension model to assess the amount of drug detached from the carrier particles during inhalation, was developed and validated using the experimental data. It could be shown, that the CIS provided a good estimate of the loss of drug due to adhesion to the carrier particles and the loss of drug on the cascade impactor walls. Small deviations between the theoretical and experimental mass median aerodynamic particle diameters however were found. These deviations were shown to be mainly due to the experimental error introduced by the cascade impactor, and that the error due to the experimental adhesion measurements is negligibly small. Hence, the CIS developed could be a useful tool in early development stages of dry powder inhalations to predict the in vitro aerodynamic performance of drug particles.