(330c) Tailoring Desired Powder Properties in Pharmaceutical Development By Hswm-Facilitated Polymorph Transformation

2018 AIChE Annual Meeting (abstract)

Tailoring Desired Powder Properties
in Pharmaceutical Development by HSWM-facilitated Polymorph Transformation

Authors:   Tyler
Wilson, Troy Reynolds, Brandon Brown, Bal Kang, Stacy Bremner, Michael Ischay, Chiajen
Lai*

A model compound X with an intrinsic crystal
habit of large particle size and highly agglomerated input (freebase) presents
significant process challenges in the final salt formation, polymorph
conversion, and product particle size control. 
High shear wet milling (HSWM), which is commonly used in the
pharmaceutical industry as a preferred technique for PSD control, was found to
greatly enhance the kinetics of polymorph transformation.  A number of operation parameters for HSWM
(tip speed, shear frequency, mill configuration), typically used in other
conventional milling applications, were studied in a design of experiment (DoE)
setting in order to determine a suitable scale-up factor.  Other process variables such as batch
turnover rate were also evaluated for performance prediction.  The investigation, in combination with
quantitative PAT monitoring, indicated a robust particle size control is
achieved through the act of shearing, instead of milling, by the HSWM.  This insight has shed light on process
understanding and consequently impacted the long term design strategy. A
scaling model is proposed and its prediction is demonstrated on multiple
batches at various scales.    

*Presenting author