The development of a growth regime map for a novel reverse-phase wet granulation process.

The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.

An assessment of powder pycnometry as a means of determining granule porosity.

A powder pycnometry method, using a commercially available instrument (GeoPyc® with DryFlo® displacement media), was evaluated as a means of measuring the envelope density of hydroxyapatite (HA) granules in the size range of 75-8000 µm. The aims of this study were to (1) investigate the reproducibility of the DryFlo® powder particle size and consolidation properties, (2) determine the number of preparation cycles required before test measurements should be taken, (3) compare the powder pycnometry method to the reference mercury porosimetry method and (4) investigate the effect of granule size on envelope density measurement. DryFlo® was shown to have a reproducible particle size when sampled at multiple locations across three separate containers. A minimum of 1 preparation cycle should be used to ensure consistent packing of the DryFlo® and HA granules. DryFlo® density was found to be insensitive to consolidation forces in the range of 10-100 N. The powder pycnometry method could be linearly calibrated against the reference mercury porosimetry method when considering polydisperse HA granule samples. However, when analyzing narrow particle size fractions limitations in the powder pycnometry method were noted resulting in a reduced particle size range of 1850-4050 µm that could be linearly calibrated against the mercury porosimetry method.