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What causes ‘Sticking’ in pharmaceutical tablets?

  1. Oct 2, 2017 #1
    Pharmaceutical tablets are formed by compressing powder in a die by metal punches until a compact is formed. The term ‘Sticking’ refers to a phenomenon that results in the adherence of material onto the punch faces and die wall even after the metal has left contact with the tablet. I am interested in getting opinions and recommendations from this scientific community on what you think is causing ‘Sticking’ and how to test or study the fundamental mechanisms by which this occurs. A brief introduction into this problem is appended below if you wish to know more on this.

    A brief introduction on 'Sticking'
    One of the most common oral solid dosage forms is the tablet, like TUMS® or TYLENOL®. Tablets are formed by compressing powder in a die by metal punches until a compact is formed. It sounds easy, but tablet compaction is often met with all kinds of issues that result in the formation of tablet defects. For example: air entrapment in the compacting powder, improper filling of the die, inhomogeneity of the density distribution in the compact, various kinds of breakage of the tablet after its been compacted and/or ejected, etc.

    One of the type of tablet defects that I study is called ‘Sticking’. The term ‘Sticking’ refers to a phenomenon that results in the adherence of material onto the punch faces and die wall even after the metal has left contact with the tablet. Meaning, pieces of the tablet remain stuck on the punch face as the punch retracts off the tablet surface after it is compacted. This issue produces tablets with defective surfaces and ends up costing lots of time, money and delays to supplying medicines to patients.

    Typically, the powder that is compacted into a tablet consists of at least three main components: the active drug crystals (like acetaminophen in TYLENOL®), a very small quantity of solid lubricant (like magnesium stearate to improve the flow properties of the powder) and a filler material (like microcrystalline cellulose). To give you an idea, the composition of the powder may be 20:79:1 drug:filler:lubricant.

    Sticking is often a very gradual process. Meaning, you may see that the punch tip appears clean even after making 100 tablets but then it slowly forms a very faint powdery deposit after making ~500 tablets which will continue to accumulate and eventually become a clearly visible film. Typically, the adhered material is almost entirely composed of the drug. There are several factors known and/or hypothesized to play a role in the phenomenon of ‘Sticking’. Some of these include: particle size, morphology, melt temperature of drug, crystal fragmentation, interaction energies between crystal facets and metal surface, triboelectric charging, crystalline to amorphous transformation upon deformation, moisture, punch surface roughness… and the list goes on. For this reason, ‘Sticking’ is known to be a complex multi-faceted issue that can be caused by various factors contributing at once.

    To date, there is no concrete understanding of ‘Sticking’ and how to mitigate this issue. In fact, many of the solutions are sort of shoot-in-the-dark not-so-scientific approaches which may work for one kind of drug and not for another. I am interested in getting opinions and recommendations from this scientific community on what you think is causing ‘Sticking’ and how to test or study the fundamental mechanisms by which this occurs. I would also love to get feedback from folks with different academic and industrial backgrounds than mine to help sort of think-outside-the-box.

    Tablet Compaction.png Sticking.png
     
  2. jcsd
  3. Oct 3, 2017 #2

    berkeman

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    I didn't read the full post (TL), but in many types of molding and casting operations, a "release compound" is used to pre-coat the mold surfaces. Has this approach been looked at by this industry?

    https://en.wikipedia.org/wiki/Release_agent
     
  4. Oct 3, 2017 #3
    This is actually something that has been attempted. For example, folks have tried to use a spray system that will spray solid lubricant (like magnesium stearate) on the punch surface prior to compaction. It essentially acts as a 'release agent' in this scenario. Spraying a solid lubricant may have its own challenges especially when many thousands of tablets need to be manufactured on a rotary tablet press. However, this is certainly an idea and there are folks trying to develop/improve this. Thank you very much for you response!
     
  5. Oct 4, 2017 #4

    Nidum

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    What about active systems ?

    Some possibilities :

    Devices which swing in at programmed intervals and clean the punch and die sets mechanically .

    Devices which swap out the punch and die sets at programmed intervals and replace with refurbished clean sets .

    This sort of solution is common on CNC machine tools . Generally because tooling has become blunt rather than fouled but principles are the same .
     
    Last edited: Oct 4, 2017
  6. Oct 4, 2017 #5

    Bystander

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    What are the stresses? Have you actually got some fatigue/failure? Pinching by micro-cracks isn't going to give you any separation,
    but it might be a place to start.
     
  7. Oct 5, 2017 #6

    DrClaude

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    How about coating the faces of the punch (with a material Teflon?). Or using a different material (like a ceramic)?

    Also, instead of filling the punch with a premixed powder, one could layer the powders such that the faces of the punch are in contact with only the filler (hopefully, one could find a filler that reduces sticking).
     
  8. Oct 8, 2017 #7
    This is a great idea! Not sure how effectively it would work, but to my knowledge this has not been tested. Thank you for sharing your thoughts.
     
  9. Oct 8, 2017 #8
    The punch coating is a great idea! punch manufacturers are actively working to come up with coatings that would mitigate sticking. However, this is still a shoot in the dark approach. A particular coating may work for one compound and not another. Teflon has been used but is not too common or preferred due to excessive wear from 1000's of compaction cycles. Ceramic may work... i'm not sure. The compressive stress during tablet compaction is typically on the order of 200 to 500MPa. Ceramics are brittle and may crack or chip and cause issues. Maybe someone else who knows ceramics better can chime in. Thank you very much for sharing your thoughts.
     
  10. Oct 8, 2017 #9
    The compressive stress during tablet compaction is typically on the order of 200 to 500MPa. There is definitely failure and hence the separation of part of the tablet however i am not sure about fatigue. Drug crystals can have slip systems and can cleave along slip planes. But there is no true understanding of the the real mechanism(s) of failure in 'Sticking'. Would you please elaborate on what you mean by micro-cracks? Thank you very much for sharing your thoughts.
     
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