A research report submitted to the Faculty of Health Sciences,
University of the Witwatersrand, Johannesburg, in partial fulfilment of the
requirements for the degree of
Master of Science in Medicine in Pharmaceutical Affairs
Johannesburg, 2014 / Aim
The first step in a wet granulation process is dry mixing. This step has the objective of ensuring that
all the raw materials are mixed such that the end product is homogeneous. Dry mixing in a high shear
mixer instead of a blender saves cost. However, the mixing parameters have not been well
researched. Dry mixing parameters that are currently used, have been established through
experience, trial and error and in-process testing. Alexander and Muzzio (2006) confirms this by
stating that there are currently no mathematical techniques to predict blending behaviour of granular
components without prior experimental work; therefore, blending studies start with a small-scale, try-itand-
see approach. Even though they are referring to blending, the same is also true for dry mixing.
Both processes are the mixing of powders. Therefore the aim of this research was to develop
parameters for dry mixing, based on experimental work.
Methods
Using a Saral rapid mixer and wet granulator (Saral Engineering Company, India), experiments were
performed according to a 24 two-level Plackett-Burman Design method, to determine the effects of
different blades (mixer/impeller and chopper) speeds and mixing times on the homogeneity of the
mixtures containing different ratios of two powders that have different densities and particle sizes.
One of the powders mixed, was enalapril maleate. This was chosen as it can be assayed. Samples
were taken from the bowl and tested for assay. The mix for a specific experiment is homogeneous if
the results of all 7 assayed samples are within 10 % of the target % w/w value and the % Relative
Standard Deviation (% RSD) of the 7 results is less than or equal to 5,0 %. The outcome was being
measured in % RSD. A lower % RSD indicates a more homogeneous mix.
The parameters developed, will be beneficial to pharmaceutical companies as it can assist them to
improve accuracy, consistency and quality of granular mixes. The experimental method used can
serve as an example for future experiments.
Results
The results indicated that impeller blade mixing speed and mixing time are the two factors that have
the biggest impact on the homogeneity of a mix in a high shear mixer. Chopper blade speed was also
found to be significant, but less than the above two parameters mentioned. Optimal parameters were
predicted.
Conclusion
As there are many parameters to be controlled during dry mixing in a high shear mixer, a statistical
design method is suitable to establish the parameters that would have the most impact on the end
result. Statistically it was found that mixing speed of the main impeller and chopper blades and overall
mixing time are the three factors that have the biggest impact on the homogeneity of a mixture. The
mixing time and impeller blade speed have proven to be more significant than the chopper blade
speed. Concentration was found to be insignificant. For our experiments and for the specific
granulator used the following optimal parameters could be deduced: Impeller blade set at 191 rpm,
chopper blade set at 2002 rpm and mixing time set at 3.01 minutes.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/17424 |
| Date | 16 April 2015 |
| Creators | Van Wyk, Elzaan |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf, application/pdf, application/pdf, application/pdf |
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