(68b) Rational Design and Scale-up of Batch Lubrication Processes for Immediate Release Formulations

Purpose: To provide stepwise guidance for lubrication of pharmaceutical powders through the development of a unifying model which captures lubrication effects during blending and compression. 

Methods: Literature models of powder properties following lubrication blending over a range of scales and conditions were reviewed.  Additionally, a new model was developed by lubricating pharmaceutical powders in a tablet press feed frame.  Lubricated powders were compressed on a development-scale rotary tablet press (Kilian T100) with varying throughput and feed-frame paddle rotation speeds.  The resulting tablets were measured for tensile strength and a feed frame lubrication sensitivity model was developed.  The two models were then combined to create an integrated lubrication understanding framework.  

Results: Lubrication process design and scale-up guidelines were developed that addressed the selection of the appropriate amount of lubricant, the impact of equipment design (scale & principle of operation), and the need to select processing conditions that will result in the consistent manufacture of product possessing the desired extent of lubrication.  To provide quantitative guidance to this end, a new unified model was developed which captured the effect of lubrication on pharmaceutical powders during blending and compression. 

Conclusions:  The proposed stepwise approach outlines the current state-of-the-art for conventional tablet blend lubrication processes, and embodies the principles of Quality-by-Design and risk-based drug product development. As such it is recommended as the starting point for scientists undertaking the development of immediate release tablet formulations.