Small molecule, high impact: the role of water in the crystallization of paclitaxel

DOI: 10.1002/jps.23404

Authors: Liana Vella-Zarb (Max Planck Institute for Solid State Research) , Ulrich Baisch (University of Newcastle Upon Tyne) , Robert Dinnebier (Max Planck Institute for Solid State Research, Stuttgart)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Pharmaceutical Sciences , VOL 102 (2) , PAGES 674-683

State: Published (Approved)
Published: November 2012
Diamond Proposal Number(s): 6749

Abstract: Paclitaxel is an important antineoplastic drug, which is used widely in the treatment of many forms of cancer. The crystal structures of the anhydrous form and the hemihydrate were determined from laboratory X-ray powder diffraction data, whereas the dihydrate was solved from single-crystal synchrotron diffraction data. Intermolecular spaces allow for the inclusion of loosely bound water molecules, which are then lost easily upon heating. All three forms were found to crystallize in the orthorhombic spacegroup P212121, with Z′ = 2. The unit cell parameters were found to be a = 9.6530(3) Å, b = 28.1196(8) Å, c = 33.5378(14) Å, and V = 9103.5(5) Å for the anhydrous form (363 K); a = 9.6890(2) Å, b = 28.0760(4) Å, c = 33.6166(8) Å, and V = 9144.7(3) Å3 for the hemihydrate (333 K); and a = 9.512(6) Å, b = 28.064(16) Å, c = 33.08(2) Å, and V = 8829.0(9) Å3 for the dihydrate (120 K). Water loss occurs in two steps between 120 K ≤ t ≤ 363 K. The thermal stability of the hydrates and accompanying unit cell changes were observed in situ via temperature-resolved X-ray powder diffraction and thermogravimetric analysis.

Journal Keywords: Paclitaxel; Cancer; X-Ray Powder Diffractometry; Solid State; Polymorphism; Crystallography; Rietveld Refinement; Taxanes

Subject Areas: Chemistry, Medicine, Biology and Bio-materials


Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 27/09/2012 23:02

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Life Sciences & Biotech

Technical Tags:

Diffraction Single Crystal X-ray Diffraction (SXRD)