Systematic Approach to High Dosage Formulation Development for Continuous Direct Compression

Continuous direct compaction for high dosage formulations is a challenging topic. The understanding of the raw material properties and identification of the critical material and process parameters is key to predicting a continuous manufacturing process and implementing control parameters. A systematic strategy has been developed to enable formulation and process design for poorly flowing active pharmaceutical ingredients (API). Currently, high dosage formulations are manufactured mainly via wet granulations including various processing steps. The length of process makes it more time consuming, costly and challenging to minimise process deviations relative to direct compression A case study using a poor flowing model API at a high drug loading (~ 50 wt%) was used to evaluate the strategy. The approach adopted is material sparing, targeted and time efficient. The accumulated material database can be used to expedite future developments. A series of characterisation techniques have been used to analyse various pharmaceutical powders to identify their flow and compaction behaviour. This information was used to predict blend behaviour and inform formulation design. Independent lab scale predictors of manufacturing performance have been developed on a benchtop compaction simulator. The success of this strategy has been shown by scaling up to an R&D rotary tablet press maintaining all critical quality attributes (CQAs).