Optimization study and discussion of response
Once the initial screening study and the augmented CCD study were concluded, sufficient data had been generated to support
an optimization study. The optimization process provides an opportunity to set the two responses, hardness and weight, to
desirable outcomes and allow Design-Expert software to produce recommended experiments that should yield tablets with the
desired criteria. Optimization is the ultimate goal of any experimental-design process. In this case, a target hardness of
7 kP and a weight of 190 mg were selected. The upper and lower factor limits from the augmented CCD study were used during
the optimization process, and eight experiments were performed.
Table VI: Analysis of variance for augmented central composite design model according to tablet weight.
The results of this study were mixed. Two runs were acceptable, but the other six produced undesirable hardness. The results
of the optimization experiments are shown in Table VII. For added benefit, output responses from the tablet press were recorded
for precompression force and main compression force in kN. Although it would have been preferable to have several more factor
setpoint combinations to produce the desired tablet characteristics, several hypotheses can explain why the other experiments
did not produce the desired tablet.
Table VII: Optimization study results.
The predicted response 3D plot shows how optimization run 7 responded at the given factor setpoints shown in Table VII. In
Figure 7, a small window is evident on the concentric rings in the x axis. The window shows that a limited range of error is permissible to maintain the desired hardness and weight values. The
area in red on the 3D contour represents the most desirable response. Further studies could be performed in the small red
region with the intent of clearly defining the acceptable factor tolerances when moving a product into a manufacturing environment.
Figure 7: 3D response plot for optimization run 7.
High turret speeds can cause tablet weight to decrease, especially if the feed-frame paddles are turning slowly. This effect
occurs when insufficient powder is placed into the tablet-punch die in the brief amount of time that it is under the feed
frame. It is also possible that at such high radial velocities, high centrifugal forces push the powder fill out of the die.
When precompression or main compression forces were high, tablet defects were observed in the form of lamination. Lamination
likely occurs when the tablet is compressed too quickly, causing the tablet to separate in layers. This defect was often associated
with high turret speeds. Lamination may also result from inadequate removal of the entrapped air in the die cavity during
the precompression step. A tablet that has begun to laminate may provide false readings on the hardness tester. Lamination
was more prevalent when main compression forces were less than precompression forces.
Experienced formulation scientists and production operators understand the complexities of tablet-press operation, and this
knowledge can help them to prepare targeted experimental designs that would produce optimization responses with great flexibility
in the processing specification setpoints. As the processing specification setpoint error gets larger, the likelihood that
the batch will be rejected for undesirable responses decreases. The larger the allowable variation from the processing setpoint,
the greater the chance of producing an acceptable tablet.