Predicting the quality of powders for inhalation from surface energy and area

Purpose. To correlate the surface energy of active and carrier components in an aerosol powder to in vitro performance of a passive dry powder inhaler. Methods. Inverse gas chromatography (IGC) was used to assess the surface energy of active (albuterol and ipratropium bromide) and carrier (lactose monohydrate, trehalose dihydrate and mannitol) components of a dry powder inhaler formulation. Blends (1% w/w) of drug and carrier were prepared and evaluated for dry powder inhaler performance by cascade impaction. The formulations were tested with either of two passive dry powder inhalers, Rotahaler(R) (GlaxoSmithKline) or Handihaler(R) (Boehringer Ingelheim). Results. In vitro performance of the powder blends was strongly correlated to surface energy interaction between active and carrier components. Plotting fine particle fraction vs. surface energy interaction yielded an R-2 value of 0.9283. Increasing surface energy interaction between drug and carrier resulted in greater fine particle fraction of drug. Conclusions. A convincing relationship, potentially useful for rapid formulation design and screening, was found between the surface energy and area parameters derived from IGC and dry powder inhaler performance.