Scale-up of pharmaceutical spray drying using scale-up rules: A review

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Scale-up

Background:

• Spray drying is a common pharmaceutical manufacturing technique.
• Existing research extensively covers process-formulation impacts on powder attributes.
• However, limited data exists on spray drying process scale-up.

Purpose of the Study:

• To analyze existing spray drying scale-up literature.
• To scrutinize the fundamental transformations (atomization, drying, gas-solid separation) from a scale-up perspective.
• To propose a rational approach for spray drying process development and scale-up.

Main Methods:

• Literature review of scale-up attempts.
• Analysis of spray drying transformations using non-dimensional parameters and multi-scale analysis.
• Identification of key response variables for successful scale-up.

Main Results:

• Identified key scale-up variables: droplet size distribution, outlet temperature, relative humidity, separator pressure loss coefficient, and collection efficiency.
• Advocates for mechanistic models and scale-up rules over trial-and-error.
• Provides a roadmap for bridging the scale-up knowledge gap.

Conclusions:

• Successful spray drying scale-up requires consistent key response variables across scales.
• Mechanistic modeling offers a rational approach to establish design spaces for spray drying.
• This work provides a framework for effective pharmaceutical process development and scale-up.