(189d) Establishing Meaningful Alarm Limits for a Continuous Direct Compression Process

Jenna Brandon, Daniel Blackwood, Patrick Daugherity, Alexandre Bonnassiuex, Giuseppe Cogoni, Kai Lee, David Wilsdon

Pfizer Worldwide Research and Development, Groton, CT 06340 USA

Abstract

A science of scale study has been completed to support the establishment of meaningful alarm limits for a continuous direct compression process. Within this study, small scale blends (~30g each) were prepared with each of the formulation components (active ingredient, diluents, disintegrants, and lubricants) purposely varied in multi-variate combinations above and below the target formulation concentrations. These blends were subsequently compressed into tablets and the quality attributes of the drug product was evaluated with off-line analytical techniques (such as dissolution profile, tablet physical properties) as compared to proposed drug product specifications.

These evaluated formulation composition ranges were utilized to provide control limits for each formulation component with respect to individual gravimetric feeder alarm limits and predicted concentration levels of the formulation components at the output stream of the in-line powder mixer. Additionally, a residence time distribution (RTD) model is utilized by the in-line mixer. RTD studies have been completed to characterize mixing behavior across a range of process parameters, formulation components and API characteristics ensuring a robust manufacturing process with flexible capabilities.