Understanding the effect of mixing on the performance of dry powders for inhalation
1Emmace Consulting AB, Scheelevägen 22, S-223 63 Lund, Sweden.
2Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
This study investigates the influence of the mixing process on the dispersibility of adhesive mixtures for inhalation in terms of the fine particle fraction, FPF, with focus on formulations comprising a ‘coating agent’, blended in a high shear mixer. For such systems, an increase in dispersibility as function of the mixing time, followed by a decrease at longer mixing times, is observed. It was found that the applied mixing energy, ME, calculated from carrier particle mass, the radius of the mixing bowl, mixing time and speed, is a key factor. Based on ME, the FPF behavior can be modeled mathematically and rate constants for the increasing and the decreasing part of the FPF curve can be obtained. Formulations without a coating agent blended in a high shear mixer can also be modelled based on ME. In this case, the resulting equation is an exponential decay function. The exact mechanisms behind the increasing and the decreasing parts of the FPF curve remains to be understood but it is hypothesized that the FPF increase is caused by smearing of coating agent onto the API particles. The absence of an increasing phase for formulations without a coating agent supports this hypothesis.
For adhesive mixtures blended in a high shear mixer, the mixing energy, ME, calculated from carrier particle mass, the radius of the mixer bowl, mixing time and speed, has been identified as a key factor governing the dispersibility of the API.