Johannes Khinast

The effects of material attributes on capsule fill weight and weight variability in dosator nozzle machines

The goal of this work is to identify and understand the complex relationship between the material attributes, capsule fill weight and weight variability of capsules filled with a dosator nozzle machine. Six powders were characterized and filled into size-3 capsules in three volumes of dosing chambers and at two filling speeds. Subsequent multivariate data analysis was used to identify the influence of the material attributes on the capsule fill weight and weight variability. We observed a clear correlation between the capsule fill weight and the particle size, the air permeability and the compressibility. As the fill weight decreases, more factors affect capsule fill weight. For example, the wall friction angle, the tapped density, and the particle shape proved to be important factors. Larger fill weights were more affected by density while lower fill weights by flow and friction characteristics. No correlation was found between the material attributes and the weight variability. Rather, we could also see the major effect of process parameters on capsule fill weight and weight variability.

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 powders 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.

Optical coherence tomography for non-destructive analysis of coatings in pharmaceutical tablets

Tablet coating is a common pharmaceutical technique to apply a thin continuous layer of solid on the top of a tablet or a granule containing active pharmaceutical ingredients (APIs). Coating thickness and homogeneity are critical parameters regarding the drug release rate, and consequently a direct or indirect monitoring strategy of these critical process parameters is essential. With the aid of Optical Coherence Tomography (OCT) it is not only possible to measure the absolute coating thickness, but also to detect inhomogeneities in the coating or substrate material. In this work the possible application of OCT as in-line method for monitoring pharmaceutical tablet film coating is studied. Firstly, the feasibility of OCT for analysis tablet coating is examined. Seven different commercially available film-coated tablets with different shapes, formulations and coating thicknesses were investigated off-line. OCT images were acquired by two different spectral-domain OCT systems operating at center wavelengths of 830 and 1325 nm. Since the images of both systems allow the analysis of the coatings, the OCT system employing the shorter wavelength and thus providing a higher axial resolution was selected for the further experiments. The influence of a moving tablet bed on OCT images was analyzed by considering a static tablet bed and moving the sensor head along the tablet bed. The ability to analyze the coating homogeneity is limited to a speed up to 0.3 m/s. However, determining the coating thickness and inter-coating uniformity is still possible up to a speed of 0.7 m/s.