Particular challenges
Some powders are more difficult to dose than others. One of the many challenges lies in the fact that formulations must not be altered once they were officially approved. They must therefore be processed as they are - the same applies to the target containers. In principle, the product determines the process.
The first focus is on finding a dosing system to suit the powder in question. Most Harro Höfliger machines are equipped with volumetric dosing systems, dealing with small quantities to be filled into small-sized containers, with filling levels up to 100%. Another thing are powders with particle sizes of 10µm and less: Due to the interparticle adhesion force these tiny particles flow very poorly, they agglomerate and stick to the surfaces of the filling machine.
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Hollow microspheres for inhalation
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.
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The active ingredient is attached to carrier crystals of lactose monohydrate
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.
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Lyophilized formulation for nasal application
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.
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Polymer beads with embedded active ingredient
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.
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Silver oxide for coating wound dressings
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.
Appropiate dosing system
For this reason, powder properties like the flow behavior are being tested in the laboratory first. Even in small-scale this indicates potential problems for the later full-size machine. If a powder flows poorly, the dosing chamber is insufficiently filled. This might be improved with the help of vibration, ultrasound or vacuum, and once a suitable system is found it can be scaled up to the real production machine.
More than 90% of the projects Harro Höfliger is involved in relate to medicines and medical products. It is essential to perfectly match powder and processes to ensure stability throughout the entire storage and administration period. For example, Biopharmaceuticals containing proteins and peptides are increasingly being used. They often come in the form of lyophilisates or spray-dried powders and require specific ambient conditions like a low relative humidity. If it is too low, though, electrostatic charging makes the dosing process difficult to control. Consequently, such difficult substances require the development of customized machinery.
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