A Design of Experiments for Tablet Compression - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

A Design of Experiments for Tablet Compression
The author prepared and analyzed a detailed design of experiments for the manufacture of a simple tablet formulation. The aim was to test whether tablet hardness and weight could be controlled during the compression process by adjusting certain machine parameters.


Pharmaceutical Technology
Volume 35, Issue 9


Figure 4: Half-normal plot of tablet weight.
Weight response. Tablet weight is a crucial tablet characteristic, and data analysis is necessary for this response. The half-normal plot for tablet weight using the original screening results is shown in Figure 4. The plot indicates that factors A, B, C, and E significantly affected the weight response. The analysis of variance shown in Table VI supports the plot in Figure 4.

In the next equation, R 2 is 0.9955, adjusted R 2 is 0.9945, and adequate precision is 126.423. The R 2 of 0.9955 is in reasonable agreement with the adjusted R 2 of 0.9945. The adequate precision ratio of 126.423 indicates an adequate signal, so the following equation, in terms of coded factors, can be used to establish the design space:





Figure 5: Normal plot of residuals for weight.
The 95% confidence intervals for the coefficients of each of the significant terms were verified to exclude zero, which supports the determination that all identified factors in the model equation influence the response. A normal plot of residuals was constructed to determine whether the distribution was normal (see Figure 5).


Figure 6: Residuals versus predicted plot for weight.
A residuals versus predicted plot was constructed to look for trends in the data (see Figure 6). All data points are equally distributed and are within two standard deviations from the mean, with two exceptions. One high point is 2.422 standard deviations, and one low point is –2.473 standard deviations). The two data points that lie beyond 2 standard deviations of the mean could be investigated, and these experiments may warrant being rerun to confirm the data response. The data have no potential outliers.


Appendix Figure 5: One-factor plot, tablet weight versus fill-cam height.
No two-factor interactions can be plotted, though factor E (i.e., fill-cam height and weight-adjustment ramp) had a significant effect on tablet weight. As can be expected, the amount of powder placed into the die cavity had a direct effect on tablet weight. This is clearly evident in Appendix Figure 5. The plot shows that as the weight ramp or fill cam height is increased, tablet weight increases.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
28%
Oversee medical treatment of patients in the US.
9%
Provide treatment for patients globally.
9%
All of the above.
41%
No government involvement in patient treatment or drug development.
13%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Source: Pharmaceutical Technology,
Click here