Pharmaceutical Manufacturing Handbook: Production and

lose in combination with either talc or magnesium stearate generally decreased as
the amount of the lubricant was increased over the concentration range of 0 – 9%.
Similar results were observed for admixtures of sodium sulfathiazole in combination
with either talc or magnesium stearate. It was also demonstrated that the tensile
strength, indentation hardness, and bonding index increased, and the brittle fracture
index decreased as the percent of microcrystalline cellulose was increased in a
mixture with sodium sulfathiazole.
The results of a study conducted by Muller and Augsburger [16] suggest that
the pressure – volume relationship determined during powder bed compression is
affected by the instantaneous punch speed profi le of the displacement – time waveform
for all materials studied, even though they deform by different mechanisms.
It appears that the instantaneous punch speed profi le of the particular displacement
– time waveform is a confounding factor of Heckel analysis.
Moisute acts as a plasticizer and infl uences the mechanical properties of powdered
materials for tablet compression. In the case of microcrystalline cellulose, at
moisture levels above 5% the material exhibits signifi cant changes consistent with
a transition from the glassy state to the rubbery state [17] . The possible infl uence of
moisture on the compaction behavior of powders was also analyzed by Gupta et al.
[18] . This work evaluates the effect of variation in the ambient moisture on the
compaction behavior of microcrystalline cellulose powder.
The work conducted by Gustafsson et al. [19] evaluated the particle
properties and solid - state characteristics of two different brands of microcrystalline
cellulose (Avicel PH101 and a brand obtained from the alga Cladophora sp.)
and related the compaction behavior to the properties of the tablets. The difference
in fi bril dimension and, thereby, the fi bril surface area of the two celluloses
were shown to be the primary factor in determining their properties and
behavior.
The compaction properties of pharmaceutical formulations can be studied experimentally
using a variety of techniques, ranging from instrumented production
presses to compaction simulators, and methods of analysis. The results are usually
plotted as porosity – axial stress functions, which is of interest to compare different
materials. However, there are some drawbacks on this type of evaluation. As mentioned
by Cunningham et al. [20] , this approach is defi cient once it considers only
the average stress along the direction of compaction, ignoring radial stress transmission
and friction.
There have been some attempts to overcome the analysis of compaction
problems, mostly by introducing numerical modeling approaches. The modeling
approaches often used in compaction analysis are (a) phenomenological continuum
models, (b) micromechanically based continuum models, and (c) discrete - element
models. The parameters that should be analyzed when tableting is under development
are as follows:
1.
2.
3.
COMPACTIBILITY 1139
Understanding the formulation and compositional effects on the compaction
process, including axial loading and unloading along with ejection
Determination of the stress distributions within the powder compact, including
residual stresses
Optimization of the tablet tooling design