Determining particle‐size distributions from chord length measurements for different particle morphologies

Abstract

A recently proposed model to determine particle‐size distributions (PSDs) from chord length measurements has been applied to different particle morphologies, namely compact, platelet‐ and rod‐shaped particles. To study these systems, chord length distributions (CLDs) were measured at varying particle size and solids concentration for each compound and were subsequently utilized to determine the system‐specific parameters. Each model was successfully applied to its respective compound such that the experimental PSDs and model predictions were in good agreement. Moreover, the effect of other variables such as agitation rate and solvent composition was investigated and found to be negligible for the specific systems tested. Finally, potential model optimizations of the general model construct have been studied. Two variants of the CLD compression step, namely principal component analysis and a geometric model have been considered as surrogate models. However, neither of these approaches yielded superior results than the previously proposed approach.

Perspectives on the Current State, Challenges, and Opportunities in Pharmaceutical Crystallization Process Development

“…There have been many efforts to mathematically relate the CLD to the PSD, but these efforts have had limited success. There has been recent progress, 50 but a comprehensive review of the state of the art in this area and further development is still needed.…”

A Physics-Assisted Data-Driven Framework for Predicting Crystal Chord Length Distributions under Arbitrary Experimental Conditions

“…In practice, however, there is no guarantee that real CLDs (RCLDs) can be described using a limited set of moments. An alternative to using CLD moments in the compression step was presented in reference , wherein the compression step was performed with principal component analysis.…”