Publication

Optimization of granule size and tablet properties in a twin screw granulator: the influence of process and formulation parameters

Sekyi, Nana K.G.
Publication Date
End of Embargo
Supervisor
Rahmanian, Nejat
Kelly, Adrian L.
Keywords
Granulation, Twin screw granulation, High shear melt granulation, High shear granulator, Design of experiments, Granule size distrubution, Differential scanning calorimetry, Tableting, Process parameters, Granule production
Rights
Creative Commons License
The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
Department of Chemical Engineering. Faculty of Engineering & Informatics
Awarded
2023
Embargo end date
Collections
Theses
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Files
18017673 Nana Sekyi - Final Thesis for Library.pdf
Adobe PDF, 16.58 MB
Additional title
Granule production and characterization via Design of Experiment approach
Abstract
Omitting the drying step and other associated processing costs in wet granulation is a benefit of melt granulation. However, twin screw hot melt granulation is rarely applied in most industries. This work details the product characteristics and optimization from melt granulation of the model materials, calcium carbonate (Durcal 65) + polyethylene glycol (PEG) 4000, and the pharmaceutical formulation, α-D Lactose monohydrate + ibuprofen + PEG 4000 via a co-rotating granulator. Product characteristics (e.g., granule yield and strength, tablet crushing force, friability, and dissolution) are determined as being both formulation and process dependent. Screw speed, number and type of mixing elements, temperature, and binder content are investigated via Minitab software (v 20.4.0.0) for their impact on product attributes. Higher temperatures and binder content are identified as statistically significant in the formation of both 125 – 1000 μm sized granules and seeded structures. Temperature determines binder viscosities and surface tensions which effectively impact granule and tablet qualities, with initial particle size also impacting tablet properties. Harder tablets of lengthy dissolution times and low drug release is observed for Pharma G and vice versa for Pharma B. A granulation mechanism is proposed with both immersion and distribution nucleation leading to formation of seeded structures though immersion type dominates. The three granulation rate processes occur only with the use of mixing elements, while conveying elements facilitate nucleation and growth in the presence of higher binder content and temperatures. Successfully manipulating particle size distribution, temperature and binder content are vital in achieving desired ngineered products.
URI
https://bradscholars.brad.ac.uk/handle/10454/20327
Version
Citation
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Link to Version of Record
Type
Thesis
Qualification name
PhD
Notes