Insight into the Mechanisms of Cocrystallization of Pharmaceuticals in Supercritical Solvents

Carbon dioxide has been extensively used as a green solvent medium for the crystallization of active pharmaceutical ingredients (APIs) by replacing harmful organic solvents. This work explores the mechanisms underlying a novel recrystallization method—cocrystallization with supercritical solvent (CSS)—which enables APIs cocrystallization by suspending powders in pure CO2. Six well-known APIs that form cocrystals with saccharin (SAC) were processed by CSS, namely, theophylline (TPL), indomethacin (IND), carbamazepine (CBZ), caffeine (CAF), sulfamethazine (SFZ), and acetylsalicylic acid (ASA). Pure cocrystals were obtained for TPL, IND, and CBZ (with SAC) after 2 h of CSS processing. Convection was revealed to be a determining parameter for successful cocrystallization with high-yield levels. TPL–SAC was selected as a model system to study the cocrystallization kinetics in the gas, supercritical, and liquid phases under different conditions of pressure (8–20 MPa), temperature (30 to 70 °C), and convection r...

[1]  R. Gobetto,et al.  Didanosine polymorphism in a supercritical antisolvent process. , 2010, Journal of pharmaceutical sciences.

[2]  Michael J. Zaworotko,et al.  Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? , 2004 .

[3]  Henrique A. Matos,et al.  Single-Step Co-Crystallization and Lipid Dispersion by Supercritical Enhanced Atomization , 2013 .

[4]  Amjad Alhalaweh,et al.  Bioavailability of indomethacin‐saccharin cocrystals , 2010, The Journal of pharmacy and pharmacology.

[5]  J. Wuest,et al.  Molecular solids: Co-crystals give light a tune-up. , 2012, Nature chemistry.

[6]  William Jones,et al.  Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding , 2009 .

[7]  I. Pentchev,et al.  Impregnation isotherms of hydroxybenzoic acid on PMMA in supercritical carbon dioxide , 2007 .

[8]  S. Velaga,et al.  Indomethacin–Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization , 2008, Pharmaceutical Research.

[9]  Luis Padrela,et al.  Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture , 2012, Drug development and industrial pharmacy.

[10]  Raj Suryanarayanan,et al.  A rapid thermal method for cocrystal screening , 2008 .

[11]  Luis Padrela,et al.  Formation of indomethacin-saccharin cocrystals using supercritical fluid technology. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[12]  David R. Weyna,et al.  Synthesis and Structural Characterization of Cocrystals and Pharmaceutical Cocrystals: Mechanochemistry vs Slow Evaporation from Solution , 2009 .

[13]  J. Wouters,et al.  Pharmaceutical Salts and Co-crystals , 2011 .

[14]  H. Uchida,et al.  Growth Phenomena of Single Crystals of Naphthalene in Supercritical Carbon Dioxide , 2004 .

[15]  Aeri Park,et al.  Use of a Glutaric Acid Cocrystal to Improve Oral Bioavailability of a Low Solubility API , 2006, Pharmaceutical Research.

[16]  F. Giordano,et al.  Solubility and conversion of carbamazepine polymorphs in supercritical carbon dioxide. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[17]  S. Laugier,et al.  Effect of CO2-antisolvent techniques on size distribution and crystal lattice of theophylline , 2011 .

[18]  Ning Shan,et al.  The role of cocrystals in pharmaceutical science. , 2008, Drug discovery today.

[19]  M. Mazzotti,et al.  Gas Antisolvent Recrystallization of Paracetamol from Acetone Using Compressed Carbon Dioxide as Antisolvent , 2004 .

[20]  M. J. Cocero,et al.  Production of Polymorphs of Ibuprofen Sodium by Supercritical Antisolvent (SAS) Precipitation , 2009 .

[21]  Dan Boström,et al.  Pharmaceutical Cocrystal and Salts of Norfloxacin , 2006 .

[22]  H. Matos,et al.  Theophylline polymorphs by atomization of supercritical antisolvent induced suspensions , 2011 .

[23]  A. Newman,et al.  Pharmaceutical Cocrystals and Their Physicochemical Properties , 2009, Crystal growth & design.

[24]  W. Jiskoot,et al.  Selective Production of Polymorphs and Pseudomorphs Using Supercritical Fluid Crystallization from Aqueous Solutions , 2007 .

[25]  G. Brunner,et al.  Solubilities of the xanthines caffeine, theophylline and theobromine in supercritical carbon dioxide , 1994 .

[26]  Henrique A. Matos,et al.  Screening for pharmaceutical cocrystals using the supercritical fluid enhanced atomization process , 2010 .