A Design of Experiments for Tablet Compression - Pharmaceutical Technology

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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


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 completely filled.

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,

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.


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