Q: How do we determine the cause of tablet capping during production and prevent it from occurring?
A: Robert Sedlock, Natoli Engineering, says:
The term capping in tablet manufacturing refers to a tablet failure, a break across the horizontal plane, that you find when performing a breaking force or friability test. Many factors can contribute to capping, including a formulation’s blend characteristics, the material’s deformation properties, and the mechanical configuration of the tablet press and tooling.
Pharmaceutical manufacturers commonly discover capping during manufacturing. However, it’s preferable to identify this problem in the developmental stage, because changing the formulation after a drug product has moved to full-scale manufacturing can be challenging. Adjusting a formulation requires following Scale-Up and Post Approval Changes (SUPAC) guidelines, which can be time consuming and may halt manufacturing.
Formulators can identify a potential capping problem by characterizing a formulation’s permeability, which is a fundamental property affecting the tableting process. Entrapped air in a powder blend can reduce interparticle bonding as well as the tablet’s final tensile strength, both of which can lead to tablet failures such as capping. If a formulation’s permeability is high, less air entrapment will occur during tableting, resulting in fewer tablet defects.
You can conduct permeability tests using a lab-scale powder rheometer. A powder rheometer measures the powder’s resistance to airflow. Using a vented piston under a range of applied normal stresses, air is passed through the powder bed. The relative difference in the air pressure between the bottom and top of the powder column represents the powder’s permeability.
A powder rheometer measures the powder’s resistance to airflow. Using a vented piston under a range of applied normal stresses, air is passed through the powder bed. The relative difference in the air pressure between the bottom and top of the powder column represents the powder’s permeability.
A compaction simulator or emulator is a sophisticated, single-punch tablet press that measures applied forces and punch displacement data under conditions similar to that of a production-scale rotary tablet press.
The simulator allows an analysis of the force displacement curves (work curves) that show the formulation’s elastic recovery after an applied load is released. It also allows the measurement of Heckel and Picker plots that identify the compaction pressure required for plasticity to occur.
These tools allow you to select the appropriate excipients to develop a robust formulation that will survive the manufacturing process with minimal tablet defects, including capping.
Tablet press configuration
You can address capping without changing the formulation by adjusting tablet press parameters such as precompression force, punch penetration, main compression force, and turret speed.
Precompression force. Precompression, or de-aeration, is a compression stage before the main compression event that forms the final compacted tablet. With precompression force, you can consolidate the particles and remove entrapped air without creating a bond between particles. The rule of thumb is that precompression force should be 10 percent of main compression force, but this rule doesn’t always work.
Common pharmaceutical materials have different consolidation behaviors, so the ideal precompression force may vary widely, depending on the material.
A low precompression force allows the removal of air between the particles, which decreases capping potential. The amount of precompression force is critical, however, because too much force can increase capping.
You can test the correct amount of precompression force by rotating the turret manually while applying only precompression force. After the compact is ejected, it should appear to be an intact tablet, but when you squeeze it with your fingers it should fall apart back into the original particles. This shows that particles have not bonded together but instead are consolidated and closely packed.
Punch penetration. The punch penetration determines how high in the die bore the tablet is compressed. Since air travels upward during compression and escapes between the upper punch tip and the die, less punch penetration reduces the distance the air must travel to escape and minimizes capping potential.
Main compression force
A decrease in main compression force can also reduce capping. When a tablet reaches its maximum compactibility, it won’t increase in strength with additional compression force. Instead, the excess compression force can reduce interparticle bonding and cause capping. In that case, reducing the compression force may fix a capping issue.
Decreasing the tablet press’ turret speed may also reduce capping. You might achieve an acceptable tablet strength on a small R&D press, but when you move to production scale, the press may use a higher compression rate or a lower dwell time. If the formulation is strain-rate sensitive, compression speed will impact the tablet’s robustness. Such formulations require slower turret speeds.
You can also modify features of the tooling to reduce tablet capping, including using tapered dies or reconfiguring the punch heads.
A tapered die allows a higher rate of air removal from the die cavity. The inner die cavity tapers outward toward the top of the die, which allows more room for the air to escape. To take advantage of this feature, adjust the punch penetration so the tablet is being compressed in the tapered area.
Punch head configuration
A new punch head configuration may remediate capping issues in the manufacturing environment. Extended punch head flats can increase dwell time—the time the tablet is under maximum compression—which can increase the tablet strength in some cases. However, recent studies published by the Natoli Institute at Long Island University have shown that reducing the head flat can resolve some capping issues at high speeds. In either case, head flats can play a major role in tablet robustness and capping potential.
Robert Sedlock is director of technical training and development at Natoli Engineering, Telford, PA, a division of Natoli Engineering. Natoli Scientific provides solutions to challenges in R&D tableting, scale-up, and manufacturing as well as customized services to solve tableting difficulties and offer support.