Predictive Stress Tests in the Scale-Up of Capsule Formulations

Abstract

In early development, supplies of bulk active are limited and capsule formulations are developed on a small scale. However they should be suitable for scale-up. In this report, the Turbula T2C is shown to mimic the prolonged stirring and stressing of powder blends in the large hopper of a dosator type machine, e.g. Zanasi LZ64. The degree of mixing affects the lubricity and wettability of capsule blends containing magnesium stearate and stressing powder blends in a Turbula T2C highlights changes in blend properties which occur on scale-up. Measuring tapped bulk density, wettability and disintegration of stressed blends identifies robust formulations which are unaffected by long “lubrication” times and scale. Changes in blend properties are influenced more by shearing energy than the extent of mixing