A new strategy of transforming pharmaceutical crystal forms.

The robust nature of network materials allows them to (for example) respond to external stimuli such as pressure, temperature, light, or gas/solvent adsorption and desorption. There is difficulty in retaining long-range order in purely molecular organic solids, due to weak intermolecular interactions such as van der Waals forces. Here, we show gas-induced transformations of the well-known pharmaceuticals clarithromycin and lansoprazole. For clarithromycin, the stimulus is capable of converting the kinetic solvate and guest-free crystal forms to the commercial thermodynamically stable polymorph with a huge saving in energy cost relative to industrially employed methods. The synthesis of the marketing form of lansoprazole involves a solvate that readily decomposes and that is stirred in water, filtered, and dried intensively. Our method readily circumvents such synthetic problems and transforms the sensitive solvate to the marketed drug substance with ease. Such expedient transformations hold great implications for the pharmaceutical industry in general when considering the ease of transformation and mild conditions employed.

[1]  Jun Liu,et al.  Gas-induced solid state transformation of an organic lattice: from nonporous to nanoporous. , 2011, Chemical communications.

[2]  E. Pidcock,et al.  Pressure as a tool in crystal engineering: inducing a phase transition in a high-Z′ structure , 2010 .

[3]  J. Atwood,et al.  Free transport of water and CO2 in nonporous hydrophobic clarithromycin form II crystals. , 2009, Journal of the American Chemical Society.

[4]  C. S. Lin,et al.  Molecular and crystal structure of an ethanol solvate of 6-O-Methylerythromycin A , 2009 .

[5]  K. Moribe,et al.  Supercritical carbon dioxide processing of active pharmaceutical ingredients for polymorphic control and for complex formation. , 2008, Advanced drug delivery reviews.

[6]  J. Atwood,et al.  Gas-induced transformation and expansion of a non-porous organic solid. , 2008, Nature materials.

[7]  Jianpeng Liang,et al.  A New Crystal Structure of Clarithromycin , 2008 .

[8]  C. Pulham,et al.  High-pressure studies of pharmaceutical compounds and energetic materials. , 2006, Chemical Society reviews.

[9]  W. David,et al.  Effect of high pressure on the crystal structures of polymorphs of glycine , 2005 .

[10]  T. Oguchi,et al.  Supercritical carbon dioxide treatment as a method for polymorph preparation of deoxycholic acid. , 2003, International journal of pharmaceutics.

[11]  Roger J. Davey,et al.  Pizzas, polymorphs and pills , 2003 .

[12]  H. Brittain Effects of mechanical processing on phase composition. , 2002, Journal of pharmaceutical sciences.

[13]  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.

[14]  A. Sivalakshmidevi,et al.  Lansoprazole, an antiulcerative drug , 2000 .

[15]  G. Stephenson,et al.  Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity. , 1997, Journal of pharmaceutical sciences.

[16]  B. Subramaniam,et al.  Pharmaceutical processing with supercritical carbon dioxide. , 1997, Journal of pharmaceutical sciences.

[17]  Yoshiaki Watanabe,et al.  Structure of 6‐O‐methylerythromycin A (clarithromycin) , 1993 .

[18]  T. Adachi,et al.  Chemical modification of erythromycins. II. Synthesis and antibacterial activity of O-alkyl derivatives of erythromycin A. , 1990, The Journal of antibiotics.