Process and product understanding of rapid and continuous wet granulation

Student thesis: Doctoral Thesis


Wet granulation is a common industrial operation for particle size enlargement, which traditionally has been performed in batch-based operations. However, the potential advantages of continuous granulation such as improved quality, rapid API sparing development and greater flexibility have drawn attention to this technology.;One of the common equipment evaluated to perform continuous granulation is the twin-screw granulator (TSG). The advantage of this equipment is the flexibility offered from the high number of possible working environments achieved by changing different sections of the screw assembly, different segment geometries or feed port locations. However, the current state of art of this technology does not yet allow the implementation into the pharmaceutical process. The introduction of this technology requires an increased knowledge of the granules properties as well as the acceptable working limits of the TSG equipment.;In this thesis, both issues have been addressed. On one side, a homogeneity factor to transform particle size distributions in a percentage easing the creation of design workspaces was developed. Also, the verification of the channel fill methodology to an 11 mm twin screw granulator and its relationship with another process parameters was explored. Furthermore, a method to use microencapsulated sensors (CAMES) whose rupture is directly dependant on their experienced shear stress was developed for first time for TSG.;On the other side, an algorithm to extract selected parts from inside the granule was developed and applied to granules obtained by both batch and continuous. In addition, the effect ofthe liquid availability and drying effect in the formation of granules was studied obtaining significant morphological differences depending on the temperature. Furthermore, it was found that nuclei obtained a different liquid to solid ratio were similar in size but different in number which suggest that the granules size is directly dependant on the liquid availability.
Date of Award4 Jun 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsEPSRC (Engineering and Physical Sciences Research Council)
SupervisorGavin Halbert (Supervisor) & John Robertson (Supervisor)

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