Quality by Statistical Control in Crystallization - Assessment of Mixing Conditions and Probability of Obtaining the Desired Particle Size

Ameessa Tulcidas, Bruno Santos, Sylwin Pawlowski, Fernando Rocha

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Reactor hydrodynamics can play a significant role in antisolvent crystallizations. In this work, the impact of suspension height/clearance ratio (H/C) and power per volume (PV) on the particle size distribution (PSD) parameters Dv10, Dv50, and Dv90 of an active pharmaceutical ingredient (API) were evaluated. The API solution was added near the liquid surface of the antisolvent with a buret, at a rate of approximately 5 mL/min, between the impeller and the reactor's wall. Statistical models were developed, and it was found that PSD parameters seem to be influenced by the H/C and PV. A relationship between the PSD parameters and the nucleation rate was also witnessed. Furthermore, different mathematical methodologies (indicator function and Monte Carlo simulations) were used to obtain a design space comprising the probability of success of having PSD parameters within specification. An operating region comprising the probability of success was estimated, which can aid in minimizing the risk of failure in antisolvent crystallization processes and consequently help reduce the financial losses caused by out-of-specification batches.

Original languageEnglish
Pages (from-to)20162-20172
Number of pages11
JournalIndustrial and Engineering Chemistry Research
Volume58
Issue number43
DOIs
Publication statusPublished - 30 Oct 2019

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