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

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Analytical Technology

Background:

• Transitioning from batch to continuous manufacturing (CM) necessitates robust process monitoring and control.
• While CM of semi-solids is established, integrating diverse Process Analytical Technology (PAT) tools at the end of the CM line remains underexplored.

Purpose of the Study:

• To continuously manufacture creams and evaluate the efficacy of in- and on-line PAT tools.
• To assess the utility of viscosity, active pharmaceutical ingredient (API) concentration, and pH measurements for optimizing a model cream.
• To investigate mixer torque as a physical property indicator.

Main Methods:

• Continuous manufacturing of a model cream.
• In- and on-line monitoring of viscosity, API concentration (using two Raman probes), and pH.
• Assessment of mixer torque.
• Systematic variation of API concentration, neutralizer amount, and mixing speed.

Main Results:

• Both Raman probes successfully detected step changes in API concentration.
• pH adjustments were effectively monitored.
• Mixer torque could not be correlated with viscosity due to the dynamic and time-dependent nature of the cream's properties.
• PAT tools demonstrated feasibility for implementation in a continuous line.

Conclusions:

• The study successfully demonstrated the continuous manufacturing of creams with integrated PAT.
• Investigated PAT tools are suitable for real-time monitoring and can support the optimization of cream composition and process parameters.
• Further research is needed to correlate mixer torque with cream properties in a continuous setting.