Pharmaceutical Technology: Controlled Drug Release, Volume 2

68 MATRIX FORMULATIONS [CH. 5
Fig. 5—Discriminant analysis.
CONCLUSION
The work previously performed [5,7] shows the importance of experimental design for reaching
an optimized formulation with a minimum number of experiments.
From experimental testing of this work we could arrive at the following conclusions.
(1) The flowability test in a Jenike cell was very sensitive to the technological modifications of
the same optimized formulation; therefore, it can be used for quality control during the
development, scale-up or production of medicaments.
(2) The variability of the porosity parameters may be used to differentiate between the processes
and to explain the variability of the dissolution parameters.
(3) There was no significant difference between trials in all the processes, indicating that
dissolution values can be reproducible; the β parameter may help to differentiate one process
from another and to evaluate the variability between trials and between tablets.
The plots of two components obtained from PCA and from discriminant analysis, revealed an
‘opposition’ between tablets obtained by wet granulation and by direct compression. In fact, the
principal component represents the curve shape of the dissolution profiles (β), which, in these two
processes, were quite different.
The Higuchi model gave the worst fit for the data because of the change of the tablet surface
during the dissolution test. With the exception of the formulation obtained by direct compression
in a rotary machine, the dissolution profiles were well fitted by the Weibull function. A high
density in the centre of the tablets may explain the sigmoid aspect of the dissolution profiles.