Dual centrifugation - A new technique for nanomilling of poorly soluble drugs and formulation screening by an DoE-approach.
The development of nanosuspensions of poorly soluble APIs takes a lot of time and high amount of active material is needed. In this publication the use of dual centrifugation (DC) for an effective and rapid API-nanomilling is described for the first time. DC differs from normal centrifugation by an additional rotation of the samples during centrifugation, resulting in a very fast and powerful movement of the samples inside the vials, which - in combination with milling beads - result in effective milling. DC-nanomilling was compared to conventional wet ball milling and results in same or even smaller particle sizes. Also drug concentrations up to 40% can be processed. The process is fast (typical 90min) and the temperature can be controlled. DC-nanomilling appears to be very gentle, experiments showed no change of the crystal structure during milling. Since batch sizes are very small (100-1000mg) and since 40 sample vials can be processed in parallel, DC is ideal for the screening of suitable polymer/surfactant combinations. Fenofibrate was used to investigate DC-nanomilling for formulation screening by applying a DoE-approach. The presented data also show that the results of DC-nanomilling experiments are highly comparable to the results obtained by common agitator mills.
['Hagedorn|Martin|M|', 'Bögershausen|Ansgar|A|', 'Rischer|Matthias|M|', 'Schubert|Rolf|R|', 'Massing|Ulrich|U|']
D002498:Centrifugation D002626:Chemistry, Pharmaceutical D004339:Drug Compounding D053758:Nanoparticles D036103:Nanotechnology D010316:Particle Size D012995:Solubility D013535:Suspensions
Dual centrifugation Nanomilling Nanosuspension Wet ball milling Design of experiments Nanocrystalline suspension Nanoparticles