Crystallisation is gaining a lot of interest in pharmaceutical industry to help
designing active ingredients with tailored physicochemical properties. Many
factors have been found to affect the crystallisation process, including process
parameters and material attributes. Several studies in the literature have
discussed the role of these parameters in the crystallisation process. A
comprehensive study is still missing in this field where all the significant terms are
taken into consideration, including the square effect and the interaction terms
between different parameters. In this study, a thorough investigation into the main
factors affecting crystallisation of a polymeric system, processed via injection
moulding, was presented and a sample of response optimisation was introduced
which can be mimicked to suite a specific need.
Three grades of pure polyethylene oxide; 20K, 200K and 2M, were first
characterised using differential scanning calorimetry (DSC), thermogravimetric
analysis (TGA), powder X-ray diffraction (PXRD) and shear rheometry. The onset
of degradation and the rate varied according to molecular weight of polyethylene
oxide (PEO). The peak melting temperature and the difference in enthalpy
between melting and crystallisation were both in a direct proportion with PEO
molecular weight. PEO200K and PEO2M struggle to recrystallise to the same
extent of the original state at the tested cooling rates, while PEO20K can retain
up to a similar crystallinity degree when cooled at 1 °C/min. Onset of
crystallisation temperature (Tc1) was high for PEO2M and the difference between
the 20K and 200K were pronounced at low cooling rate (20K is higher than 200K).
The rheometer study showed that PEO2M has a solid-like structure around
melting point which explains the difficulty in processing this grade at a low
temperature via IM. PEO20K was almost stable within the strain values studied
(Newtonian behaviour). For higher grades, PEO showed a shear thinning
behaviour. The complex viscosity for PEO2M is characterised by a steeper slope
compared to PEO200K, which indicates higher shear thinning sensitivity due to
higher entanglement of the longer chains.
For binary blends of PEO, the enthalpy of crystallisation studied by DSC was in
direct proportion to the lowest molecular weight PEO content (PEOL %) in
PEO20K/200K and PEO20K/2M blends. The effect of PEOL% on Tc1 became
slightly pronounced for PEO20K-2M blends where Tc1 exhibited slight inverse
proportionality to PEOL% and it became more significant for PEO200K-2M
blends. It was interesting to find that Tc1 for the blends did not necessarily lie
between the values of the homopolymers. In all binary blends, Tc1 was inversely
proportional to cooling rate for the set of cooling rates tested. Thermal analysis
using hot stage polarised light microscopy yields different behaviours of various
PEO grades against the first detection of crystals especially where the lowest grade showed highest detection temperature.
Visual observation of PEO binary blends caplets processed at various conditions
via injection moulding (IM) showed the low-quality caplets processed at mould
temperature above Tc1 of the sample. The factors affecting crystallisation of
injection moulded caplets were studied using response surface methodology for
two responses; peak melting temperature (Tm) and relative change in crystallinity
(∆Xc%) compared to an unprocessed sample. Mould temperature (Tmould) was the
most significant factor in all binary blend models. The relationship between Tmould
and the two responses was positive non-linear at the Tmould ˂ Tc1. Injection speed
was also a significant factor for both responses in PEO20K-200K blends. For Tm,
the injection speed had a positive linear relationship while the opposite trend was
found for ∆Xc%. The interaction term found in the RSM study for all models was
only between the injection speed and the PEOL % which shows the couple effect
between these two factors. Molecular effect was considered a significant factor
in all ∆Xc% models across the three binary blends. The order of ∆Xc% sensitivity
to the change in PEOL% was 3, 5 and 7 % for 20K-200K, 200K-2M and 20K-2M.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/18783 |
| Date | January 2019 |
| Creators | Mkia, Abdul R. |
| Contributors | Gough, Timothy D., Isreb, Mohammad |
| Publisher | University of Bradford, Faculty of Life Sciences. School of Pharmacy and Medical Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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