Powder Technology, Vol.339, 641-650, 2018
Particle engineering of needle shaped crystals by wet milling and temperature cycling: Optimisation for roller compaction
Purpose: The purpose of this work is to demonstrate a process for the alteration of the shape of needle shaped crystals of an active pharmaceutical ingredient (API) using a combination of wet milling and temperature cycling. The effect upon powder handling metrics of the shape alteration approach was quantified and the impact upon a subsequent roller compaction process step demonstrated. Methods: Particle shape was altered through a combination of wet milling and temperature cycling. Image analysis was used to measure the length and width of the needle shaped particles. Powder handling was quantified using shear cell and bulk density measurements. Roller compaction trials were used to demonstrate improvements in processability. Results: Particle width and length could be altered independently of each other with appropriate application of wet milling and temperature cycling. Powder handling metrics were greatly improved by the shape alteration. A partial least square model was developed to help explain the link between particle properties and powder handling metrics. Conclusions: A process for altering the shape of needle shaped particles was developed. This process manifested in an improvement in both powder handling metrics and the processability of the powder as demonstrated by roller compaction. (C) 2018 Elsevier B.V. All rights reserved.
Keywords:Particle engineering;Roller compaction;Image analysis;Flowability;Partial least squares modelling