KNOW-HOW  

Pack­aging tricky powders

Some pow­ders are more dif­fi­cult to package than others. The experts at Harro Höfliger find the appro­priate solu­tion for all pow­ders. And if needed, a new inven­tion is cre­ated – always true to the motto: The product deter­mines the process.

Some­times even the smartest powder specia­lists at Harro Höfliger are tearing their hair out. For example, when due to par­ticle shape or size, sta­bility or den­sity, the mate­rial to be filled simply cannot be dosed into the des­ig­nated cap­sule or cavity of the blister strip.

For Dr. Karl­heinz Sey­fang, Prin­cipal Con­sul­tant at Harro Höfliger, these stub­born pow­ders are pre­cisely what makes his work so exciting, and ducking the issue is not an option: “Changing for­mu­la­tions post appro­val is not pos­sible,” he explains. “We must work with them the way they are – the same applies to the target con­tainers. This is why the product deter­mines the process. Ulti­mately, we find a solu­tion for everything.”

Tricky pow­ders

These are some of the most stub­born materials:

Hollow micros­pheres have an extremely low den­sity (< 0.03 g/ml). For com­par­ison: The den­sity of sugar is 20 times higher. Despite their spher­ical shape, the par­ti­cles only have a mod­erate flow rate and are sen­si­tive to high rel­a­tive humidity.

Such for­mu­la­tions con­sist of active sub­stances in the form of small “crumbs” which are attached to car­rier crys­tals of lac­tose mono­hy­drate. In a powder inhaler, the active ingre­dient par­ti­cles must detach from the car­rier. Unfor­tu­nately, this can already happen during the dosing process which bears the risk of de-mixing.

Lyophilized for­mu­la­tions clump together when rel­a­tive humidity is too high. In addi­tion, the flow prop­er­ties of the powder are neg­a­tively affected by the unfa­vor­able par­ticle shape: The flakes can mechan­i­cally interlock.

Polymer beads with an embedded ­active ingre­dient must not be dam­aged, as that would change the release rate. This for­mu­la­tion is injected, so filling must be aseptic. Due to the high mate­rial value of the product, it has to be pos­sible to com­pletely empty the machine’s dosing system.

Silver oxide for coating wound dress­ings is an accu­mu­la­tion of extremely fine par­ti­cles. The inter­par­ticle adhe­sion forces cause the mate­rial to flow poorly, as it tends to clump together and stick to machine parts during processing.


The appro­priate dosing system

The search for solu­tions starts with the right dosing system. In most cases, spe­cialty machines by Harro Höfliger are equipped with vol­u­metric dosing sys­tems. Dr. Sey­fang: “We often work with very small dosing quan­ti­ties which have to be filled into small target con­tainers – some with a filling level of 100 %. This is a real chal­lenge when it comes to pow­ders with par­ticle sizes smaller than 10 µm.”

With these tiny par­ti­cles, the inter­par­ticle adhe­sion forces are pre­dom­i­nant. The mate­rial flows very poorly, clumps, and adheres to the sur­faces of the machines that come into con­tact with the product.

In order to find out how pow­ders behave during pro­cessing, their prop­er­ties are deter­mined in the Harro Höfliger lab­o­ra­tory where, among other things, their impact on the flow behavior is exam­ined. This is then put to the test on table-top ver­sions of common filling systems. 

“Once a suit­able system has been found, we scale up to a pro­duc­tion machine.“Dr. Karl­heinz Sey­fang, Prin­cipal Con­sul­tant at Harro Höfliger

Here, we can already see on a small scale what can later lead to prob­lems on a large scale. If pow­ders flow poorly, the dosing chamber will not be filled prop­erly. Vibrating devices, ultra­sound or picking up the powder with suc­tion under neg­a­tive pres­sure can help. Dr. Sey­fang: “Our table-top dosing sys­tems already meet many require­ments, and once a suit­able system is found, we scale-up to a pro­duc­tion machine.”

Suit­able frame­work conditions

Knowing the powder prop­er­ties is not just impor­tant for exact dosing. Pow­ders and processes also have to har­mo­nize so that later they run smoothly on the machine. More than 90 per­cent of the projects that Harro ­Höfliger is involved in, relate to med­i­cines and med­ical prod­ucts. Their sta­bility must be guar­an­teed over the entire stora­ge and admin­is­tra­tion period.

This can only be ensured if the man­u­fac­turing con­di­tions are right. For example, the share of bio­phar­ma­ceu­ti­cals con­taining pro­teins and pep­tides as active ingre­di­ents is increasing. They are often used as lyophilizates or spray-dried pow­ders which can only be processed in an envi­ron­ment with low rel­a­tive humidity in order to pre­vent clumping.

If the rel­a­tive humidity is too low, static charges may occur: The dosing processes are then dif­fi­cult to con­trol since the powder par­ti­cles repel each other or stick to the dosing system. Dr. Sey­fang: “This is just one of many bal­ancing acts that we have to master. When dealing with dif­fi­cult sub­stances, we ­some­times have to develop new, indi­vidual solu­tions. We are a spe­cialty machine man­u­fac­turer for that very reason – to meet those extra­or­di­nary challenges.”

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Photo: Janine Kyofsky