The effect of material attributes and process parameters on the powder bed uniformity during a low-dose dosator capsule filling process.
The objective of this work was to assess the effect of process parameters of a dosator nozzle machine on the powder bed uniformity of inhalation powders with various characteristics during a low-dose dosator capsule filling process. Three grades of lactose excipients were extensively characterized and filled into size 3 capsules using different dosing chamber lengths (2.5, 5mm), nozzle diameters (1.9, 3.4mm), powder bed heights (5, 10mm) and filling speeds (500, 3000capsules/h). The fill weight and the weight variability of Lactohale 100 (large particles, good flowability, low cohesion) remained almost the same, regardless of the process parameters throughout the capsule filling run time. Moreover, for this powder an increase in the fill weight at a higher filling speed was observed in all cases. Fill weight variability was significantly higher for lower dosing chamber volumes at a filling speed of 3000 capsules per hour. Lactohale 220 (small particles, poor flowability, high cohesion) delivered entirely different results. After a certain run time, depending on instrumental settings, a 'steady-state' with constant fill weights and low weight variability was achieved. For this highly cohesive powder, a high dosing chamber volume requires a low filling speed in order for the powder to completely fill the dosator nozzle. Moreover, it was established that a dosing chamber length of 2.5mm and a powder bed height of 10mm were required due to the powder's high fill weight variability over time, while the dosator size had no effect on it. In summary, the layer uniformity, the fill weight and the weight variability strongly depend on the powder characteristics and the instrumental settings. The results indicate that Lactohale 220 requires special attention during low-dose capsule filling. The study presents excellent insights into the effect of material attributes and process parameters on the layer uniformity and the quality of end product.
Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria; Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria.
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Stranzinger
Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria.
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Faulhammer
MG2, Via del Savena 18, 40065 Pian di Macina di Pianoro, Bologna, Italy.
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Calzolari
MG2, Via del Savena 18, 40065 Pian di Macina di Pianoro, Bologna, Italy.
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Biserni
University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
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Dreu
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, 40225 Düsseldorf, Germany.
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Šibanc
Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria; Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria.
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Paudel
Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria; Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria. Electronic address: khinast@tugraz.at.
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Khinast
D000280:Administration, Inhalation; D002214:Capsules; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D013678:Technology, Pharmaceutical / Q000379:methods*
D002214:Capsules; D005079:Excipients; D011208:Powders; D007785:Lactose
Dosator nozzle machine; Inhalation powders; Low-dose capsule filling; Powder bed uniformity