TY - JOUR

T1 - Continuous Manufacturing of a Polymer Stabilized Emulsion Monitored with Process Analytical Technology

AU - Qwist, Pernille Kjaergaard

AU - Sander, Camilla

AU - Bostijn, Nils

AU - Jessen, Vibeke

AU - Rantanen, Jukka

AU - de Beer, Thomas

PY - 2020

Y1 - 2020

N2 - Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process interfacing at the end of the CM line has not been demonstrated. The goal of this work was to continuously manufacture creams and to investigate whether in- and on-line measurement of viscosity, changes in the concentration of active pharmaceutical ingredient (API), and pH could be used to support optimization of a model cream product. Additionally, the torque of the mixers was assessed for determination of the physical properties of the cream. Two Raman probes with different probe optics were compared for characterization of the API concentration. The API concentration, amount of neutralizer, and mixing speed of the CM line were systematically varied. Both the PhAT probe with a larger sampling volume and immersion Raman probe with a smaller sampling volume could detect the step changes in the API concentration. The torque from the mixer was compared with the viscosity measurements, but the torque signal could not be correlated with the viscosity due to the dynamic nature of the polymer conformation and the time-dependency of this property. Adjustment of pH of the cream could be monitored with the current installation. The investigated PAT tools could be implemented into a continuous line and, further, be used to support the optimization of a model cream composition and related process parameters.

AB - Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process interfacing at the end of the CM line has not been demonstrated. The goal of this work was to continuously manufacture creams and to investigate whether in- and on-line measurement of viscosity, changes in the concentration of active pharmaceutical ingredient (API), and pH could be used to support optimization of a model cream product. Additionally, the torque of the mixers was assessed for determination of the physical properties of the cream. Two Raman probes with different probe optics were compared for characterization of the API concentration. The API concentration, amount of neutralizer, and mixing speed of the CM line were systematically varied. Both the PhAT probe with a larger sampling volume and immersion Raman probe with a smaller sampling volume could detect the step changes in the API concentration. The torque from the mixer was compared with the viscosity measurements, but the torque signal could not be correlated with the viscosity due to the dynamic nature of the polymer conformation and the time-dependency of this property. Adjustment of pH of the cream could be monitored with the current installation. The investigated PAT tools could be implemented into a continuous line and, further, be used to support the optimization of a model cream composition and related process parameters.

KW - continuous manufacturing

KW - process analytical technology

KW - Raman spectroscopy

KW - viscosity

KW - RAMAN-SPECTROSCOPY

KW - ACTIVE INGREDIENT

KW - QUANTIFICATION

U2 - 10.1208/s12249-020-01704-1

DO - 10.1208/s12249-020-01704-1

M3 - Journal article

C2 - 32449146

VL - 21

JO - AAPS PharmSciTech

JF - AAPS PharmSciTech

SN - 1530-9932

IS - 5

M1 - 154

ER -