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Powder Processing: Performance Improvements Through Co-milling

Steckel H, Stank K.

Respiratory Drug Delivery 2014. Volume 1, 2014: 89-98.

Abstract:

The performance of dry powder formulations for inhalation depends on the balance of adhesive and cohesive forces. Physical stability and dispersion of micronized active pharmaceutical ingredients in hydrofluroalkane propellants is also related to particle interactions. Micronized drugs exhibit a high agglomeration tendency, which is disadvantageous for powder aerosolization during the inhalation manoeuvre or consistent metering from a pressurized metered dose inhaler (pMDI) valve. Many attempts have been made to understand and control the forces between particles. The process of co-milling offers the opportunity to combine size reduction and surface modification, utilizing mechanical energy input. In this study, salbutamol sulphate was used as model drug and co-milled with either magnesium stearate or glyceryl monostearate. Co-micronization with both excipients resulted in a significant decrease of the dispersive surface energy and the dispersive surface energy distribution compared to the purely micronized drug. In addition, the interparticulate forces, measured using powder rheology, were reduced and the surface-modified powders demonstrated improved de-agglomeration behavior. In pMDIs, surface modified salbutamol sulphate powders resulted in a reduced sedimentation rate and a high volume sediment. Surface modification of drugs using co-milling proved to be a useful technique to improve product performance.