Powder Dosing Good Vibrations in Dosing
Precision and flexibility over speed — this is what is needed in manufacturing test preparations for clinical studies. With an eye to these requirements Harro Höfliger has developed an automatic powder dosing system for microvolumes. PharmaTEC talked to Dr. Elke Sternberger-Rützel, Head of Pharma Services, about the trick with piezoelectric crystals and the ideal application.
It is all about dosage — Paracelsus knew that back in the day, and the principle is still a decisive stage in the career of a potential drug. Not too much, not too little, but effective – the clinical studies that determine this are elaborate and the drug administered to test subjects is often produced manually. The preferred presentation is capsules, as these can be flexibly filled. For clinical studies, they can be produced with differing volumes of powder in order to determine the optimal dose.
Manual Capsule Filling is Often Still the Norm
Filling capsules is often done by hand because the sample batches are too small for mechanical filling or because a different volume is needed for each capsule, which makes automation difficult. Anyone who has ever filled and sealed a hard gelatin capsule, possibly still in the isolator, with a highly active API knows what patience it takes and that a steady hand is required with the spatula. But now there are real alternatives.
“We have seen that ‘pure API’ is increasingly being filled for clinical studies. Pharmacists primarily want flexibility, precision and as little residue as possible,” Dr. Elke Sternberger-Rützel, Head of Pharma Services at Harro Höfliger, explains. There are good reasons for these needs, as Sternberger-Rützel knows all too well from her customer visits.
Dosing trials to discover the most appropriate dosing system for new active ingredients are part of her daily work. This is why she knows that at the start of development of the active ingredient, only limited amounts are available — particularly if it involves completely new molecular compounds. Syntheses are developed in parallel with the first dosing studies, and there are only a few grams of the substance to be tested. “In this phase the substance is very expensive and valuable. This is why we want to avoid waste at all cost,” Sternberger-Rützel explains.
The Trick With the Piezoelectric Crystal
Dosing small defined quantities of powder, whether in vials or capsules, is a decisive step in the development of a drug. And this is exactly what Harro Höfliger engineers have set out to do. The result is Micro Vibe, a dosing system whose most striking characteristic is revealed in the name. It doses microvolumes with extreme precision and minimal loss of powder by means of a vibrating capillary.
Controlled by a gravimetric balance, the system doses on the “fill-to-weight” principle, in quantities from half a milligram upward. The key is the piezoelectric crystal drive, which excites vibration in the filling capillary and transports the powder dose in microportions. If the piezo drive stops, a product bridge develops in the capillary and the flow of powder stops immediately.
The dosed quantity over time (mass flow) depends on the powder characteristics and the frequency and amplitude of the applied vibration. “The principle makes possible a high degree of precision,” Sternberger-Rützel explains. To dose different powders exactly, the developers use a modular design for the capillaries. This makes it easy to adapt them to the powder characteristics.
Dosing at the Touch of a Button
There are all sorts of possibilities in the handy unit — above all, for automation. The target weight can be programmed via HMI. As the weighing cell is coupled to the drive via a feedback loop, dosing is done simply at the touch of a button.
The high level of automation simplifies handling and keeps down the number of format parts. The powder reservoir above the delivery channel is variable and can also be one way, which makes sterile dosing possible. Various containment stages are also possible — in the early stage of development, the final potency of the active ingredient is often still unknown.
From Semi-automatic to Automatic Dosing
Micro Vibe was developed several years ago as part of doctoral research, and was previously available as a semi-automatic tabletop device. “Now we have taken the next step and integrated Micro Vibe as a dosing scale in the fully-automatic capsule filling machine Modu-CLS,” Sternberger-Rützel explains. The machine can fill over 1,000 capsules an hour, offering a platform for all phases from early development through clinical batch production to commercial production.
“With the trolley system we can make possible a simple change in dosing method, if desired for later production,” Sternberger-Rützel explains.
Micro Vibe is undergoing its baptism by fire at a contract manufacturer which makes clinical samples for early phases. This is why the flexibility of the dosing system is extremely important.