Robert Sedlock explains the value of tablet press instrumentation
The solid dosage development and manufacturing process is a combination of art and science. With modern instrumentation and sophisticated software systems, the science is prevailing. Here, we discuss tablet press instrumentation and how researchers can shorten development times and proactively identify scale-up and manufacturing issues.
An instrumented tablet press is comprised of many components that are summarised below. Although the focus of this article is to describe the benefits of an instrumented tablet press, it is important to understand that a quality system is critical. Garbage in is garbage out. The data acquisition and analysis software of an R&D tablet press displays incorrect results just as attractively as it displays correct data.
A well-designed force transducer responds only to the force that is being measured, so the placement and design of the transducer are critical. For example, a pre- or main compression transducer is designed to measure the force that is being applied from the tool punch head to the compression roller. The roll pin that is supporting the roller can be manufactured with strain gauges. The material of the roll pin or spring element (the area where the strain gauge is applied) is also essential and is dependent on the expected force range. The force range on the main compression event is typically much higher than the force range expected for pre-compression. The elastic modulus, or the slope of its strain rate curve, is an important element of the spring. The elastic modulus will be much lower for a pre-compression transducer. The transducers response should be sensitive and linear throughout its range and show minimal hysteresis, good thermal stability, and an acceptable return to zero when the load is removed.
The function of the signal conditioner is to amplify the transducers small millivolt signal. This assembly requires a power supply, amplifier, analogue to digital converter, and filters.
The software of an R&D tablet press should provide a user interface that monitors real-time in-process data and records a large of amount of data in an organized manner. Some software packages, such as Natoli’s AIM Data Acquisition & Analysis software for
R&D tablet presses, provide graphical plots to evaluate a formulation’s tabletability, compressibility and compactibility. An example of the compressibility profile plot is displayed in Fig. 5. This program is also equipped for press-to-press emulation, where it will match the compression event of two different machines, which is a valuable tool for
the scale-up process.
Single station instrumentation
During the early product development stage, an instrumented single station tablet press (Fig. 2) will help characterise material deformation properties that can, in turn, allow science-based decisions in the formulation development process (illustrated in Fig. 3). A single station tablet press consists of one upper and lower punch and the die. One advantage of the single station tablet press is that it only requires a few grams of material. Instrumentation for single station tablet presses should include upper and lower punch force, ejection and residual radial die wall force, take-off sticking force, punch displacement, and temperature.
Another type of single station tablet press is a compaction emulator that is designed to match the compression times of a high-speed manufacturing rotary tablet press. Fig. 4 depicts an example of a compaction emulator. The emulator obtains all the instrumentation benefits of a single station tablet press, but it also provides this data at matched compression times of a high-speed rotary press. Fig. 7 depicts representable data from an instrumented single station tablet press and emulator.
Rotary press instrumentation
The next step in the development process is to transfer the product to an instrumented small-scale rotary tablet press (see Fig. 1). These machines are a scaled-down version of the manufacturing press and only require a few hundred grams of material. This allows the study of the product behaviour throughout the complete rotary press cycle. Data obtained from this step includes compaction profiles and strain rate scalability studies, as displayed in Fig. 6. The instrumentation on a rotary press includes pre- and main compression forces, ejection, and take-off sticking forces.
The pre-compression and main compression readings play a significant role in analysing the product consolidation and compaction phase where air is removed from the product, particles are deformed, and interparticulate bonding occurs. At this stage, it is critical to understand the product’s failure limits with tablet strength, capping, and lamination, friability, disintegration, and dissolution times.
After the compression and decompression stages, the tablet is ejected from the die. The ejection force is a product of the residual radial die wall force and coefficient of friction between the compact and die wall. High ejection forces can cause premature wear to the punches, press cams, and cause tablet quality issues. The most common remedy for high ejection forces is increased levels of powdered lubricant in the blend (e.g. magnesium stearate). The lubricant level should be optimised as an excessive amount can cause tablet capping, friability issues, and higher disintegration times. This study can be achieved by recording the ejection forces with incrementally increased compression forces. To perform this study with accurate data, the ejection transducer must be a “full-travel” design especially if the lower compression roller is adjusted to change tablet thickness and compression force. A full-travel ejection design will provide an accurate millivolt signal across the full range of the ejection sensor. It is common for some press manufacturers to use a button load cell that only captures the data in one small area and a compaction profile study will report incorrect data.
The last phase of the tablet cycle is the tablet take-off or removal from the lower punch face. Take-off is the phase where tablet picking or sticking may occur. An instrumented take-off bar permits measurement of this force and detects early signs of sticking. The force required to release the tablet from the lower punch face is normally in the order of a few Newtons and will require a very sensitive sensor. This sensor is typically manufactured with a material that exhibits a very low elastic modulus (e.g. aluminium). Additionally, semiconductor strain gauges allow more than 20 times the sensitivity output of a standard foil strain gauge.
Tablets are regarded as complex drug delivery systems and to underestimate the importance of their design, development, and manufacture will certainly invite significant issues at some stage of development or product life. Instrumented tablet presses and data collecting software packages are crucial in the success of the tablet manufacturing process.
Robert Sedlock is with Natoli Engineering