Browsing by Author "Muirhead, G."

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    In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)
    (MDPI, 2018-09-23) Schlindwein, W. S.; Bezerra, M.; Almeida, J.; Berghaus, A; Owen, M.; Muirhead, G.
    This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV– Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented.
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    Pharmaceutical excipients properties and screw feeder performance in continuous processing lines: a Quality by Design (QbD) approach
    (Taylor and Francis, 2018-09-19) Santos, B.; Carmo, F.; Schlindwein, W. S.; Muirhead, G.; Rodriguez, C.; Cabral, L.; Westrup, J.; Pitt, K.
    Screw feeder performance is a critical aspect in continuous manufacturing processes. Pharmaceutical excipients, such as mannitol, microcrystalline cellulose, lactose monohydrate, and anhydrous dibasic calcium phosphate can present problems in ensuring a continuous stable feed rate due to their sub-optimal flow properties. In alignment with Quality by Design (QbD) goals, the aim of this work was to identify and explain critical sources of variability of some powder excipients delivery by screw feeding, in particular to continuous processing lines. Pharmaceutical excipients with a wide range of material properties were selected, and the impact of their flow and density properties on screw feeder performance was investigated. The analysis of the powder conveying by the screws was performed at different hopper fills and different screw speeds. A multivariable model involving bulk density (CBD) and parameters from FT4 dynamic downwards testing (SI) and dynamic upwards testing (SE) explained 95.7% of excipients feed rates (p<.001). The study gathers valuable information about the screw feeder performance and input materials properties that can help process understanding and QbD-based development of solid dosage forms in continuous processing lines.