HP 8012a

A pulser is a nice thing to have if just for checking loop stability sometimes, it don't have to be perfect

Sounds like my approach to modelmaking.

Yeah, things don't go as well when the clean room guys are sneaking into the tool core for a smoke. ;)

Cheers

Phil Hobbs

"Quest" (TV Network) just aired a show, "Modern Marvels", in which such a device was shown in use. Apparently it's a rerun of a show from ~6 mos ago. I can't seem to find it online (in a free venue).

It would have been more interesting if they'd shown how tape rules are "exercised", hammer handles broken, screwdriver tips sheared off, tool finishes abraded, etc.

For folks used to seeing things done with "conventional" units of measure, it would be eye-opening!

They *do* use some "laboratory" tools to augment their collected data. E.g., rockwell hardness tester to determine the hardness of the steel used in the tool, etc. And, the fixtures are calibrated to produce reproducible tests -- so 1135 hammer strikes today represents the same amount of wear that it did 30 years ago, and a tape rule dropped from 50 inches experiences the same sort of impact shock that it did

30 years ago, and...

What's particularly interesting is how many tools are easily broken by careless users. A "nominal" male can easily tear the tip off a #0 Philips screwdriver. And, most can do that on a #1 tip as well! But, at #2 and larger, you really need to be a bit of a gorilla... (and capable of holding the screwdriver's tip *in* the screwhead lest it "cam out")

And, I suspect everyone has a cabinet tip screwdriver whose blade is no longer flat (overtorqued, bending the ends out of the plane of the flats). Or, a handle that "spins" on the shaft (cuz you tried to apply excessive torque with a pair of vice grips)? Or, a wood chisel that seemed like it would be a great tool for cutting aluminum gutters? Or, a screwdriver handle that has been cracked because someone thought it would make a good *chisel*?

Ans: you monitor something that correlates well with the parameters of the tablet that are important to the regulators AND your own QC.

In addition to being concerned with the amount of actives in the tablet, regulators are concerned primarily with *consistency* (!) of actives in a tablet, overall weight, dissolution time and disintegration time. They're not going to let you sell a bottle with 300mg tablets and

100mg tablets on the argument that the 300mg tablet just has 200 extra mg of binders and lubricants in its excipients! [Your QC will step in before the regulator ever sees such an abomination]

Actives can only be determined by assay -- which is destructive in nature. As are dissolution and disintegration tests.

All of these tests are far too slow to keep up with the production rate of a high speed tablet press (1M+ tablets/hour). But, you can get an insight into some of them -- weight, disintegration time (and other attributes that may be of interest in certain products -- like hardness for effervescents) -- by monitoring the *forces* encountered by the tablet at various stages of its formation and production.

[There's no need to express forces in engineering units -- as long as the calibration is consistent from press to press, lab to production, etc. Early controllers had an analog meter that showed the current state of the process -- with "percent deviation" labels (percent of WHAT?)]

As you are dealing with a constant geometry (the cavity in which the tablet is formed), higher forces indicate more material (granulation) must be present in that cavity. Lower forces correspond with lower amounts of material. I.e., you have a good predictor of *weight* (part of the scale up process is characterizing the relationship of force to tablet weight in the lab, before releasing to manufacturing). And, as such, you can put limits on measured forces to determine which tablets are likely over/underweight. And, can do this at production speeds, dispatching "bad" tablets on the fly while keeping good tablets ("swatting" the bad ones off to the side).

You can also learn a lot about the condition of the tooling that you are using (each product has a different set of tools) to determine wear and other "maintenance" issues (e.g., a broken punch tip is bad news as it means there's likely a tablet with a shard of metal in it!).

[There's a second school of thought that applies a constant force to the tablet during formation and monitors the resulting thickness, in real time -- by monitoring the motion of the compression rollers as the tablet's tooling passes between them (not using engineering units but, rather, fixed thresholds determined in the lab, at scale up).

But, these require significant mechanisms to move at reasonably high rates... I seriously wonder if they can be as sensitive as simply monitoring forces.

They also suffer from not being able to address all issues that force monitoring can detect -- like the force required to eject a formed tablet from its die (to detect barreling of dies and a crude indication of capping).]

If the tablets are going to be *coated*, then friability is hugely important (as a coating pan subjects the tablets to high abrasive forces). So, while not directly controlled for regulators, it eventually factors into the quality of the tablet (if regulator notices your coated tablets are "all coating" and "little tablet"!)

Because you are dealing with repetitive processes, you're concerned with how repeatable/consistent that process is. Is swaging station #7 producing a wider distribution of tip shear strengths than station #2? Why??

This is particularly important for a tablet press which can actually be ~100+ presses rolled into one! A 75 station press has 75 sets of tools -- upper, lower punches and a die per station. Each has manufacturing tolerances and experiences wear at different rates (based on its "tableting history").

So, a manufacturer makes sure he keeps each upper, lower, die together -- along with noting which station they occupied -- so their results are more repeatable on the next run (imagine the number of mix-and-match combinations possible!).

But, each station is measurably different in terms of physical characteristics. So, any information you observe about the production of a tablet on station #1 doesn't directly translate to the production of a tablet on station #2 -- just a few ms later! A longer punch can make the force higher (or lower -- depends on which punch) for the same amount of "fill"

So, ANY CONTROL ACTIONS that you take to keep the tablet weight (as expressed by compression force) based on observations of the formation event for station #1 can be "wrong" for the tablet being formed by station #2! Repeat...

[We've actually had customers disable the control system to determine if it might be INCREASING variability in tablets! In practical terms, you end up severely overdamping the loops to ensure the process doesn't oscillate purely as a consequence of the variations in *tooling*! Hence the value of looking at the distributions of forces (weights) per-tooling-station and using THAT information to decide when the process is stable.]

A tablet press is often double-sided -- meaning a tablet is formed on the front side of the machine while another is being formed on the back side. So, stations #1 and 38 are each in the same state of tablet formation; ditto #2 & 39...

But, the front and back sides of the machine have different cam profiles, wear patterns, etc. -- due to mechanical tolerances. And, different feeders, control loops, etc. So, a tablet formed by the punches in station #1 on the FRONT side of the press can have different characteristics than a tablet formed in that station when it's on the BACK side of the press.

And, if you're using a two (or three!) sided press to make a bi-layer (tri-layer) tablet, the observations of one "side" of the tablet's production directly factor into the observations of the second (third) side!

It is a **delightful** control system problem! Someday, they'll be able to weigh individual tablets at the 2M/hr rate and much of this will be unnecessary (though likely retained as an inner control loop).