An Investigation of the Blending Strategy and Design Space of Interactive Mixtures for Use in Inhalers

  • Dr David Morton, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia
  • Dr Shyamal Das, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia
  • Dr Ian Larson, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia
  • Stephanie Phan, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia
  • Cindy Ling, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia
  • Professor Peter Stewart, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, VIC 3052, Australia, Australia

    • Background and Purpose: The majority of dry powder inhaler (DPI) formulations comprise a ternary system of large lactose carrier particles, blended with fine lactose and micronized drug. Blending these components is a critical processing step in the creation of a stable, consistent and effective product: but despite such importance, the effect of blending on product performance is poorly understood. We hypothesize that the fine lactose provides a matrix to hold the micronized drug, preventing an unfavourable direct adhesion to the carrier. Consequently, over-blending or incorrect blending order may reduce formulation performance. This study investigated the influence of mixing on the blend structure and dispersion of two different micronized drugs (with different affinity for lactose surfaces) from ternary dry powder inhaler formulations.

    Method: A pre-blend of fine lactose and drug was prepared followed by a secondary blending of this with the carrier. Samples were taken as a function of time of the secondary blend, and assessed for content uniformity and for aerosol performance (Fine Particle Fraction: FPF).

    Result: A decrease in FPF on extended blending of over 10% was observed for the drug where drug-lactose affinity was greater than drug-drug. This change was not observed for the less adhesive drug on extended mixing.

    Conclusion: The observations supported our hypothesis, and demonstrated that an optimum design space can be identified, which can be defined by mixing parameters, and which is related to the mix structure.