Re-designing the colistimethate sodium Twincer® for large-scale production

Re-designing the colistimethate sodium Twincer® for large-scale production

Floris Grasmeijer1,2, Paul Hagedoorn1 & Anne Haaije de Boer1


1University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, Groningen, 9713 AV, the Netherlands

2PureIMS B.V., Ceintuurbaan Noord 152, Roden, 9301 NZ, the Netherlands



The disposable Twincer® dry powder inhaler was designed and developed to disperse high doses of pure micronised drug for pulmonary administration, such as antibiotics. In this study we tested vacuum drum filling with the OminidoseTM as powder filling principle for the large-scale production of the Twincer. We studied the effect of powder densification and pelletisation with this technique on the dose emission and dispersion with the Twincer. Reproducible dosing of pure micronised colistimethate sodium was possible with the production scale OmnidoseTM, despite the fact that poor powder flowability resulted in large dosing variations with the lab scale OmnidoseTM TT. The vacuum drum filling process resulted in powder pellets with considerable structural integrity at the partial vacuum pressures required for reproducible dosing. Even with small boreholes of 3.6 mm3, which restricted the size of pellets formed during drum filling, the powder passageways in the Twincer were clogged by the pellets during dispersion. A new Twincer model was developed with wider powder passageways, improved air flow through the dose compartment and improved circulation in its air classifiers. With this newly developed Twincer the pellets resulting from drum filling with the OmnidoseTM could be successfully emitted and dispersed, which enables the large-scale colistimethate sodium Twincer production. The considerable cost and risk involved in adapting a dry powder inhaler to changing formulation properties during upscaling stresses the importance of taking into account large-scale production processes during the small-scale development phase of dry powder inhalation products.

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