The bulk volume changes of powders by granulation and compression with respect to capsule filling

Abstract

Experiments were performed to study the possibility of predicting the bulk volume changes of a powder bed due to granulation and/or low compression, to aid the development of powder filled hard gelatin capsules. Granulation techniques used were a high speed mixer/granulator and an oscillating granulator. For each of a series of typical filler powders and the granules produced from them, the tapped volume and the Kawakita constant a were determined on the basis of tap density volumetry. The Kawakita constant was also obtained from low compression experiments using a Höfliger and Karg powder plug simulator. Only the granules produced in the high speed mixer/granulator partly provided a reduced tap volume, whereas the processing by an oscillating granulator resulted generally in an increased tap volume. For the decrease in volume, a limiting value of the tap volume of the original powders of 1.4 cm 3/g appears to exist. Powders with a tap volume below this threshold cannot be densified by granulation, whereas the degree of possible volume reduction increases with an increase in tap volume above the limiting value. After application of a sufficient number of taps, Carr's compressibility index and the Kawakita constant a are similar in value. However, the Kawakita constant a is increased by on average 5% if determined using low compression. Thus, the application of the Kawakita equation has no advantage over the use of Carr's compressibility index as an indicator of possible volume reduction. Therefore, an estimate of the volume reduction due to low compression can be found by adding 5% to Carr's compressibility index. A combination of granulation and compression to further densify a powder failed in providing smaller plug volumes. Hence, if a reduction in capsule size is the only reason to use a densification method, low compression is preferable to granulation.