Porton publication on polymorphic crystallization kinetics study and control

Recently, Porton team published a peer-reviewed article in Crystal Growth & Design, a journal of the American Chemical Society (ACS), titled “Methodology of Crystallization Kinetics Investigation for Designing Isolation Process of Pure Metastable Polymorph.”

The paper presents a useful methodology to generate critical experimental data on polymorphic crystallization kinetics, enabling right-first-time process design and control for robust production of pure metastable polymorph. Conducted by Porton’s Global Chemical Engineering & Technology (GCET) department under the leadership of Dr. Jian Wang, this work represents another advancement in Porton’s particle engineering capabilities.

This study tackles a common challenge in controlling the critical quality attributes (CQAs) of active pharmaceutical ingredients (APIs): the formation of undesired polymorphs during crystallization. Isolating the pure metastable crystalline form can deliver benefits such as an improved dissolution profile and/or better downstream processability, yet it is typically more difficult than isolating the stable form. To enable right‑first‑time process design for robust API isolation, the authors present a practical methodology to generate critical fundamental data and mechanistic understanding of system thermodynamic and kinetic properties—information that is often scarce at the early stages of drug development.

Developed while addressing the separation of either member of a polymorphic pair with nearly overlapping solubility profiles, the methodology includes:

(a) Determining the critical transition temperature (Tt) of an enantiotropic polymorphic pair by measuring polymorphic conversion kinetics using in situ Raman spectroscopy;

(b) Assessing nucleation kinetics of the metastable polymorph at temperatures below Tt using a polythermal method. The resulting critical data enable rational process design and control to isolate a pure polymorph — particularly the metastable form within a lower temperature range.

As a leading global CDMO, Porton’s related research appears not only in Crystal Growth & Design (CG&D) but also in Organic Process Research & Development (OPRD) and other international journals. Committed to driving sustainable pharmaceutical R&D and manufacturing through technological innovation in small molecules, peptides, oligonucleotides, and other new types of drugs, Porton continues to provide innovative, reliable solutions to global partners, Enabling Earlier Access to Good Medicines.