This study demonstrated that tablet hardness and weight could be controlled during the compression process with proper adjustment
to certain machine parameters. Tablet compression is a complex process in solid-dosage manufacturing. An experimental design
is a useful tool, especially to the inexperienced user. Experimental design provides great insight into how all of the factors
interact and what responses those interactions produce. To an experienced operator, experimental design provides a tool for
generating processing-specification setpoints that have large tolerances so that manufacturing batches produce a safe and
high-quality product for the patient with minimal rejection and rework. In this study, five factors were selected for all
experiments, and the otherwise unknown relationships and interactions were discovered during the experimental process. As
a formulator gains knowledge and experience in tablet compression, he or she can use experimental design tools such as Design-Expert
with great success when the interactions between the factors are understood.
High turret speeds can result in reduced tablet weight if the feed-frame paddle speed is insufficient. High speeds can also
result in tablet lamination if the precompression forces are too high. In production environments, high tablet speed is most
desirable because it results in high throughput. Manufacturers must strike a balance between producing robust tablets and
maintaining high production rates.
Tablet presses normally use paddle feeders as opposed to gravity feeders. It is necessary to maintain sufficient paddle speed
to ensure that the tablet die is properly filled. If the paddle speed is too high, it can overwork the formulation and cause
content-uniformity failures. If the paddles pass through the blend too quickly, they can cause the constituents to separate
because of their various densities. This effect may be most prominent in ungranulated direct-compression blends. In the most
extreme cases, powder overworked through high-speed feed-frame paddles can be subject to shear forces, which can discolor
the granulation by overheating the material.
Precompression force is a measure of how much force is imparted to the tablet punch through the precompression zone to tamp
down the powder and slightly compact the blend before main compression. This experimental design process showed that light
tamping force is preferable to high precompression force. The goal is not to form the tablet at this step, but to remove a
significant amount of air in the powder bed to minimize the potential for tablet lamination.
Main compression force is similar to precompression force. Main compression rollers are often larger in diameter than precompression
rollers. The larger diameter means that the tablet punch set spends a longer amount of dwell time in the main compression
zone forming the tablet. Because high-speed presses have short compression zones, it is typical for a production tablet press
to have large diameter compression rollers to extend the dwell time for as long as possible. To incorporate large diameter
compression rollers, tablet-press manufacturers must increase the overall turret or die-table diameter to accommodate the
larger compression rollers.
The weight-adjustment ramp is an adjustable factor that depends on the fill cam that has been chosen. Fill cams are often
chosen according to the size of the tablet being produced. This setting most directly affects how much the final tablet will
weigh. For heavy tablets, it is sometimes necessary to increase feeder paddle speed to ensure that the tablet-die cavity is
Because tablet lamination was the most common defect, further studies could develop a relationship between establishing limits
for precompression force and turret speed to produce tablets that are most likely to be free from this defect.
Matthew N. Bahr is an investigator at GlaxoSmithKline, 1250 S. Collegeville Rd., Collegeville, PA 19426, tel. 610.917.7648, email@example.com
Submitted: Mar. 14, 2011. Accepted: May 16, 2011.
Citation: When referring to this article, please cite it as "M.N. Bahr, 'A Design of Experiments for Tablet Compression,'
Pharmaceutical Technology Europe 23 (9) 72-81 (2011)." This article was first published in Pharmaceutical Technology Europe's
September 2011 print edition and will be published in Pharmaceutical Technology North America's October 2011 print edition.