Compression of coated pellets is a practical alternative to capsule filling. The
current practice is to add cushioning agents to minimize the stress on the
coated pellets. Cushioning agents however add bulkiness and reduce the
overall drug loading capacity. In this study, we investigated the performance
of compressed coated pellets with no cushioning agent to evaluate the
feasibility of predicting the coat behaviour using thermo-mechanical and
rheological analysis techniques. Different coating formulations were made of
ethyl cellulose (EC) as a coating polymer and two different kinds of additives
were incorporated into the polymeric coating solution. Triethyl Citrate (TEC)
and Polyethylene glycol 400(PEG400) were used as plasticizers at different
levels to the coating formulations (10%, 20%, 30%). Thermal, mechanical
and rheological measurements of the coating film formulations were
achieved to investigate the effect of plasticizers. Thermal gravimetric
analysis results (TGA) showed higher residual moisture content in films
plasticised with PEG 400 compared to their TEC counterparts. Differential
Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA) and
Parallel Plate Shear Rheometer (PPSR) were used to study the influence of
the level and type of plasticisers incorporated in coating film formulation on
the performance of the coating film. In this study, both DSC and DMA were used to investigate the Tg for each film coating formulation in order to
evaluate the effect of the additives. In general DMA results for the Tg value
of the films were always higher by 10-20% than those measured by the DSC.
Furthermore, clamp size and the frequency of the oscillation have an
influence on the evaluation of Tg. Complex viscosity for different coating film
formulations revealed that the shear hinning gradient changes with
temperature and plasticiser type and concentration. The value of complex
viscosity from DMA and PPSR exhibits power law behaviour. The rheological
moduli were indirectly affected by the level of plasticiser. There was a
discrepancy between the complex viscosity results obtained from both DMA
and PPSR at similar temperature but they follow the same trend. The non
plasticized polymer showed a 10 time higher complex viscosity values when
measured by DMA over that measured by PPSR. The difference was smaller
in plasticized films but it was not consistent. Therefore a consistent
coefficient to correlate the DMA and PPSR couldn’t be accurately determined
Coated pellets were compressed and key process parameters were
evaluated. The obtained results revealed that the coating thickness has a
significant effect on the release profile of the final products. It was found that
by increasing the coating film thickness, the percentage released decreased.
Also the compression force has lower influence on the drug release profile,
while the dwell time has very low effect on the percentage release from the
final products. Optimum release profile was obtained at a coating level of 5.5%
w/w and a compression force of 4700N
In conclusion, the elasticity of the plasticised EC films in this study meant
that the internal stress is not dissipated during compression and the dwell time range that was used in this experiment. Increasing the thickness
therefore was necessary to enhance the strength of the film and avoid
cracking. The mechanical and rheological profiling was helpful therefore to
understand the behaviour of the coated pellets and predict the film properties
at various steps of the process of coating and compression (i.e., various
shear rate regimes). Experimental design approach to studying the key
process and formulation parameters helped identify the optimum values for
the process.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/17459 |
| Date | January 2019 |
| Creators | Benhadia, Abrehem M.A. |
| Contributors | Grimsey, Ian M., Isreb, Mohammad, Gough, Tim, de Matas, Marcel |
| Publisher | University of Bradford, University of Bradford, Faculty of Life 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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