(551a) A Rapid, Materials-Sparing Approach to the Exploration of a Roller Compaction Process Design Space

Roller compaction (RC) is a time and material intensive process commonly used to improve the overall processing behavior of formulations. The typical approach to identifying target processing conditions on a pilot- or production scale system can easily consume kilograms of formulation, and the material consumption associated with system startup and shutdown further preclude effective in-process measurements. These issues can be magnified during efforts to establish a design space according to the principles of QbD, where, for example, a broad range of material property inputs may be evaluated to assess their impact on both downstream process behavior and product performance.

Here we demonstrate the application of a well-established scale down approach to roller compaction simulation in order to evaluate the influence material attributes of a spray dried dispersion (SDD) incur on RC processing and tablet compression behavior. The approach couples a compaction simulation of the ribbon formation process with a ¼-scale replica of an in-line rotary mill to yield granules with densities and size distributions analogous to what is produced on a Gerteis Mini-Pactor roller compactor. Intragranular blends of a constant composition were prepared using SDD lots of varying bulk densities and particle size distributions, and each blend was compressed to form simulated RC ribbons of varying target porosities. All ribbons were subsequently milled under common granulation conditions, and tablets were prepared from these granulations to evaluate both the compression behavior and in vitro dissolution performance of each final system. This materials-sparing methodology enables the exploration of the relationship between SDD properties and simulated roller compaction conditions across a broad design space, resulting in the establishment of statistical models which describe the influence of these factors on meaningful attributes of the final drug product.