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

Augmented study approach

The screening-study analysis helped determine a model equation that successfully describes the design space. The hardness and tablet weight models had R 2 values close to 100%. The models were significant, with at least 95% confidence in the results. The centerpoint runs showed minor curvature in the design space, and an augmented experimental study with additional centerpoints would help determine its effect, since only three centerpoint runs were performed during the screening study. The screening study also showed no evidence that an upper or lower limit had been reached for the hardness or the tablet weight. An augmented study allows for the outer limits of the original screening study to be broadened to expand the factor limits and eventually aid in optimization.

A central composite design (CCD) was selected for the augmented study to enable a response-surface method approach to optimization. Design-Expert software was used to prepare the augmented study factor limits and experimental run sheets. For the augmented study, an additional 15 runs were added to the original screening study of 19 runs, with new upper and lower limits. The 15 augmented runs included five centerpoint runs. For the 10 remaining runs that were not centerpoints, each factor was set at the new upper or lower limit, while the other four factors were set to their midpoints.


Table IV: Response surface method: augmented central composite design.
The limits for the augmented study are shown in Table IV. Note that the coded values for some of the factors are not at a full 2 as might be expected. The augmented experimental runs showed that if the limits for some of the factors were extended to two full experimental units, the resulting tablet would not have a measurable response. Modifications to the lower limits had to be made to produce valid data for subsequent analysis. The repercussions of not using the two full experimental units are that the standard error of prediction are no longer symmetrical throughout the design space.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

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

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
29%
Breakthrough designations
10%
Protecting the supply chain
43%
Expedited reviews of drug submissions
10%
More stakeholder involvement
10%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here