thesisposted on 15.01.2017 by Tan, Melvin
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
Wet granulation is a process of particle size enlargement whereby a liquid binder is added onto agitated powder beds to facilitate granule formation. This PhD thesis studies the foam granulation process, where the liquid binder is added as an aqueous foam. The investigation into foam granulation technology begins with a literature review on both the foam and wet granulation disciplines, followed by a series of experimental studies. The experimental studies are divided into a few different stages, starting with small scale experiments investigating single nucleus formation on static powder beds, followed by nuclei formation by a nucleation-only mechanism on real moving powder beds, foam granulation at a wide range of material and process conditions, and case studies investigating moisture and drug distribution in granules, with the primary aim to develop understanding of the mechanisms controlling (foam) binder dispersion and nucleation during foam granulation. It was discovered that the liquid drainage rate is the rate limiting step during foam penetration. Large binder concentration and/or fme powder particles are associated with a slow foam penetration process, which also give rise to the formation of fine nuclei. Nucleation via foam penetration on static powder beds was shown to provide better liquid usage and improve liquid distribution efficiency compared to the nucleation via drops on lactose powder. From the study of nuclei formation on a real moving powder bed, it was proposed that wetting and nucleation during foam granulation involves "foam drainage" and "mechanical dispersion" controlled mechanisms. Foam granulation limited to a nucleation-only mechanism was demonstrated to be able to create nuclei with uniform, narrow size distributions. The proposition of "foam drainage" and "mechanical dispersion" controlled mechanisms was verified in a series of foam granulation experiments using a wide range of material and process properties, which showed that the mechanisms can influence the initial nuclei size distribution as well as the final granule size distribution. It was discovered that increasing the liquid to solid ratio, decreasing the foam quality, increasing the primary particle size, decreasing the binder concentration and decreasing the impeller speed all have an equivalent effect in increasing the average granule size and the spread of granule size distribution. Two independent case studies have demonstrated the potential of foam granulation to achieve unifonn moisture and drug distribution in granules. Comparison between foam and spray granulation also found the differences in the wetting and nucleation mechanisms involved, and identified the major contribution to granule heterogeneity. Transfonnation and regime maps have been proposed to explain foam granulation behaviour. On the basis of the two wetting and nucleation mechanisms - "foam drainage" and mechanical dispersion" controlled mechanisms, the transfonnation maps summarizes the effects of material and process properties on the nuclei granule size distribution. A regime map is presented for to show the regimes of operation for the key rate processes involved in foam granulation and spray granulation. The maps should prove to be useful for foam granulation design, and act as the foundation for future study.