In Situ Monitoring of Cocrystallization Processes - Complementary Use of Sensing Technologies

Two in situ process analytical technologies were used to investigate a cocrystallization process: a focused beam reflectance measurement probe and a video probe. The cocrystallizations were conducted batch-wise in a stirred thermostatted vessel with carbamazepine and nicotinamide. The experiments were started in three domains of the phase solubility diagram. When carbamazepine crystals were also formed, a solution mediated phase transition from carbamazepine crystals towards cocrystals was initiated by the addition of the cocrystallizing agent (nicotinamide crystals). As the carbamazepine crystals and the carbamazepine/nicotinamide cocrystals exhibit prism-like and needle-like habits, respectively, it was possible to discriminate between them with the two sensors. The mechanisms involved in the solution mediated phase transition were investigated.

[1]  Ronald W. Rousseau,et al.  Utilization of Focused Beam Reflectance Measurement in the Control of Crystal Size Distribution in a Batch Cooled Crystallizer , 2006 .

[2]  R. Davey,et al.  Making Co-crystals-The utility of ternary phase diagrams , 2007 .

[3]  F. Puel,et al.  Cocrystal formation in solution: Inducing phase transition by manipulating the amount of cocrystallizing agent , 2011 .

[4]  Ashwini Nangia,et al.  Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals , 2011 .

[5]  G. Févotte,et al.  In Situ Raman Spectroscopy for In-Line Control of Pharmaceutical Crystallization and Solids Elaboration Processes: A Review , 2007 .

[6]  T. Leyssens,et al.  Optimization of a crystallization by online FBRM analysis of needle-shaped crystals , 2011 .

[7]  R. W. Rousseau,et al.  Observation of Polymorphic Change through Analysis of FBRM Data: Transformation of Paracetamol from Form II to Form I , 2008 .

[8]  F. Puel,et al.  Polymorphism in Processes of Crystallization in Solution: A Practical Review , 2009 .

[9]  M. Mazzotti,et al.  Model-Based Optimization of Particle Size Distribution in Batch-Cooling Crystallization of Paracetamol , 2004 .

[10]  D. O'grady,et al.  A Review of the Use of Process Analytical Technology for the Understanding and Optimization of Production Batch Crystallization Processes , 2005 .

[11]  F. Puel,et al.  Formation of co-crystals: Kinetic and thermodynamic aspects , 2009 .

[12]  B. Glennon,et al.  In Situ Monitoring of Supersaturation and Polymorphic Form of Piracetam during Batch Cooling Crystallization , 2011 .

[13]  R. Tan,et al.  Operating Regions in Cooling Cocrystallization of Caffeine and Glutaric Acid in Acetonitrile , 2010 .

[14]  F. Puel,et al.  Cocrystal Formation in Solution: In Situ Solute Concentration Monitoring of the Two Components and Kinetic Pathways , 2009 .

[15]  Sarah J. Nehm,et al.  Phase solubility diagrams of cocrystals are explained by solubility product and solution complexation , 2006 .