Intro to USP <1062>: What it is and why you should use it

A variety of factors like powder flow, material characteristics, compression pressure, turret speed, etc can affect tablet quality and production run time. Any resulting tablet defects can exacerbate production costs or even result in no product at all! Therefore, it’s necessary to characterize the tablet compression process to achieve robust tablets. First published in 2017, USP <1062> Tablet Characterization offers universal guidelines for standardized compression test procedures and use of terminology.

It's difficult to discuss tableting by only asking one question, such as: “how hard does a tablet have to be to compact successfully?” Answering this question depends on several mathematical equations, most of which are dependent on the other. To understand hardness, one must understand their formulation’s flowability and strain rate, depth of fill in a tablet press’s dies in the compression zone, which itself partially determines tablet thickness, which is determined by tablet land and, ultimately, tablet design. The entire tableting process is a sequence of events, measurements and scientific insights in which ‘one thing leads to another’. Having a data-driven process at the outset of your tableting journey, much like what USP Chapter <1062> provides, can signal if your development efforts are heading in the right direction.

USP says: ‘Although the fundamental concepts described [in Chapter <1062>] are also applicable to other processes such as plug formation during encapsulation and roller compaction, the focus of [USP Chapter <1062>] is on tableting.’

Why is USP Chapter <1062> important?

In short, USP Chapter <1062> explains the experimental methodologies used to standardize the tablet compression process. It gives R&D formulation scientists best practices for analyzing, evaluating and identifying formulations that can be compressed into a tablet. Used properly, USP <1062> paves the way for a tablet to be manufactured at scale. While it may not completely prevent issues like tablet capping from happening further downstream in the scale-up process, it does reduce these risks.

Minimize risks of capping
The term capping in tablet manufacturing refers to a type of 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.

Reduce SUPAC challenges
It’s preferable to identify capping 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. That’s precisely why developing a formulation in accordance with USP <1062> standards is important. Additionally, by isolating any potential issues to the formulation, it can make future troubleshooting processes more efficient since it rules out tooling as being a cause of any issues.

Ship products to market more quickly in the world’s largest drug market
While USP may sound like strictly a US standard, it should be considered a set of guidelines for creating a tablet that will accommodate US FDA standards for marketing tablets in phase 1 trials and beyond. It doesn’t guarantee FDA approval in any way but creating tablets in accordance with USP <1062> standards does help to make sure that a formulation developed elsewhere in the world will have a better chance of meeting US regulations.

Understanding the rotary tablet press

While USP <1062> compactability data can (and should) be collected on a single-station R&D tablet press, the integrity of that data is truly put to the test during scale-up. The goal is to create the same effective tablet on a multi-station rotary tablet press as one did on the single-station. Since this adds more independent variables to the compaction data results, understanding how a rotary tablet press works gives a deeper understanding of why those variables are important.

In a rotary tablet press, the compression cycle moves quickly, with the speed determining how effectively a powder can be compacted into a tablet. Speeds could be as fast as 100RPM, as it’s on our 32-station NP-400. The size and diameter of the turret determines the machine’s torque and tangential velocity, both of which ultimately determine the final RPMs of the turret.

Each revolution of the turret takes one station through four stages of powder compression:

1. Particle rearrangement
   Before powder enters the die cavity, the powder must be optimized for flowability. Powder sifts through the hopper, where it rests on a bed of powder, inside of a feeder. From there, a scraper blade pushes some of this powder from inside a fill cam and into a die cavity. For this to work seamlessly, a powder must have the right flowability and consistency, or else there may be a challenge in getting uniform tablet weights when they are ejected at the end of the compression cycle. The feeder does more than just over-fill the dies. If the feeder paddles are running at the correct speed, they can help to unmix blended powders, break up granules and/or compact highly moist powders to prepare them for the main compression event. The end of this stage results in reduced volume of pores (more on porosity later), which makes the powder more dense.
   
   
2. Compression
   As the upper tablet compression punch enters the die shortly after it’s been filled, it increases the amount of force being applied to the powder. When an upper punch and a lower punch converge within a die, the material within the die is pushed or squeezed together. This is where compression happens. This forces the air between the particle’s molecules (and within the die itself) to ‘exhale’ from the die. At this point in the compression cycle, peak force has not yet been reached. After peak force is achieved, the tablet press may hold this shape for a very brief amount of time (known as dwell time, measured in milliseconds), before we release pressure. This is when decompression begins.
   
   
3. Decompression
   The powder has just been compressed, and a newly minted tablet is about to be born. In a matter of milliseconds, the new tablet will expand slightly. This is a measure of the powder’s mechanic property known as elasticity or elastic recovery. Ideally, this should only be a matter of millimeters or nanometers, but if the formulation isn’t properly adjusted to USP <1062> standards, the tablet could experience one of many defects mentioned above (capping, sticking, picking and so on).
   
   
4. Ejection
   In this phase, the tablet press ejects the new tablet into a collection unit. If the tablet hasn’t been compressed properly, the ejection force in this phase could cause the tablet to cap or laminate. This is the first test of a tablet’s friability, or its ability to withstand turning and tumbling while in transit to packaging.