While I am not familiar with those two specific compounds, I would suggest some general approaches that seemed to have worked for me.  These are in no particular order; just as they come to mind.

1. Proper lubrication.  The amount and type can be important.  Even though there maybe no problems with ejection force, there may not be enough to lubricate the punches. If you use hydrogenated vegetable oil and the heat generated is more than usual, you could get melting.

2. Start with clean tooling that is in good condition.  If is pitted, this will cause problems.  If the tools have residual oil, they will promote sticking.  The oil is harder to remove than you think.  IPA (2-propanol) works well.

3. For rotary presses especially, use oil drip caps.  The oil will move down to the punch face over time or will splatter.  Drip caps work well to prevent this.  Don’t be cheap and reuse the drip caps.  That doesn’t work.

4. Particle size distribution.  Do you have a lot of fines or coarse particles?  These affect the lubrication also and may result in too much or too little lubrication.   An unusual distribution nmay require too little or too much compression force which both can cause sticking.

5. Formulation.  Trying to do direct compression might be a challenge especially if the amount of active is high (20% or more is where you need to look closely at the formulation as many compounds can’t exceed this for direct compression).  No matter what process, you need to have excipients that compress well and mix well with your actives.  If the excipients don’t mix well or mitigate the sticking properties of the actives, then you can expect problems.

6. Wet granulation works well for mitigating some of these problems.  Also, if you are wet granulating everything except a lubricant and some disintegrant, you might want to consider using less of your bulking agents in the granulation and leave some for the post granulation.  What binder are you using?  Starch and its derivatives are difficult to use without some work and can cause problems with sticking.  However, povidone results in hard granules that require a hammer mill or comminution mill (e.g Fitzpatrick mill) to size efficiently.  Hard granules don’t do well in rotary sievers.

These are some general ideas that would be a place to start to try to resolve the sticking problems.  There are a lot more, but this would be a good place to start.


J. Richard Creekmore, Ph.D, R.Ph.
US Technology Manager