Cocrystal formation in solution: Inducing phase transition by manipulating the amount of cocrystallizing agent

• Published in: Journal of crystal growth 2011-02, Vol.316 (1), p.118-125
• Main Authors: Gagniere, Emilie, Mangin, Denis, Puel, François, Valour, Jean-Pierre, Klein, Jean-Paul, Monnier, Olivier
• Format: Article
• Language: English
• Subjects: A1 Nucleation; A1 Phase diagrams; A2 Growth from solutions; A2 Industrial crystallization; B1 Cocrystals; B1 Organic compounds; Chemical and Process Engineering; Chemical engineering; Chemical Sciences; Condensed matter: structure, mechanical and thermal properties; Cross-disciplinary physics: materials science; rheology; Crystal growth; Crystals; Deviation; Engineering Sciences; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; General studies of phase transitions; Materials science; Mathematical models; Methods of crystal growth; physics of crystal growth; Nucleation; Phase diagrams; Phase diagrams and microstructures developed by solidification and solid-solid phase transformations; Phase diagrams of metals and alloys; Phase transformations; Physics; Solid phases; Solubility, segregation, and mixing; phase separation; Theory and models of crystal growth; physics of crystal growth, crystal morphology and orientation
• ISSN: 0022-0248; 1873-5002
• DOI: 10.1016/j.jcrysgro.2010.12.027

The purpose of this work was to assess the possibility of inducing solution mediated phase transition (SMPT) by manipulating the amount of the cocrystallizing agent. The cocrystal, composed of an active pharmaceutical ingredient (carbamazepine, CBZ) and its cocrystallizing agent (a vitamin—nicotinamide, NCT), was selected as a model compound. Batch experiments were performed in a stirred vessel. The solute concentrations of both CBZ and NCT were monitored using in situ ATR-FTIR spectroscopy. The introduction of NCT in dry form allowed a shift in the phase diagram, leading to an SMPT from CBZ crystals toward cocrystals. The concentration profiles gave information on the phase transition kinetics, i.e., the kinetics of nucleation, growth and dissolution mechanisms of the solid phases involved. Several situations were analyzed. This procedure could also be used to correct a process deviation that led to CBZ crystals instead of cocrystals.