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Effect of Process Parameters and Material Attributes on Crystallisation of Pharmaceutical Polymeric Systems in Injection Moulding Process. Thermal, rheological and morphological study of binary blends polyethylene oxide of three grades; 20K, 200K and 2M crystallised under various thermal and mechanical conditions using injection moulding

Mkia, Abdul R.
Publication Date
2019
End of Embargo
Supervisor
Gough, Tim
Isreb, Mohammad
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
Faculty of Life Sciences. School of Pharmacy and Medical Sciences
Awarded
2019
Embargo end date
Abstract
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.
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Qualification name
PhD
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