Using a Model-based Material Sparing Approach for Formulation and Process Development of a Roller Compacted Drug...

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Developing roller-compacted drug products often requires significant material quantities and extensive batch testing.
• Early-stage drug development faces challenges with limited drug substance availability and aggressive timelines.

Purpose of the Study:

• To introduce a material-sparing approach for roller compaction (RC) formulation and process development.
• To demonstrate the efficacy of combining material profiling with a predictive RC mathematical model.
• To reduce material consumption and batch numbers in drug product development.

Main Methods:

• Material profiling (true density, compression, friction) and a predictive RC mathematical model were employed.
• Pre-blend powder properties and RC granule characteristics guided formulation and process parameters.
• Less than 10g of model drug compound was used for initial material profiling.

Main Results:

• Successful development of roller-compacted capsule formulations at 1.4% and 14.4% drug loadings.
• Scale-up batches were manufactured using parameters derived from the predictive model.
• Measured ribbon solid fractions closely matched the model's target solid fraction.

Conclusions:

• The material-sparing approach significantly reduces material usage and batch requirements for RC drug product development.
• This method is particularly advantageous for early-stage development with limited drug substance.
• Predictive modeling integrated with material profiling streamlines formulation and process optimization.