Properties and stability of a liquid crystal form of cyclosporine-the first reported naturally occurring peptide that exists as a thermotropic liquid crystal.
A new solid-state form of cyclosporine produced by spray-drying exhibited characteristics consistent with a liquid crystal. No sharp diffraction peaks were observed by powder X-ray diffraction; however, analysis by both small-angle X-ray diffraction (SAXR) and microscopic under polarized light (PLM) confirmed the existence of two-dimensional ordered liquid crystal. Hot stage microscopy revealed a solid-to-liquid transition, in the range of 118 to 125 degrees C. Moreover, the solid-to-liquid transition showed frequency dependence by dielectric analysis (DEA), and was coincidental with a stepwise heat capacity change measured by differential scanning Calorimetry (DSC). The two-dimensional order was maintained above the solid-to-liquid transition temperature indicated by low-angle diffraction by SAXR and birefringence by PLM. However, birefringence was lost at temperatures above 170 degrees C, indicating the conversion of the liquid crystal into an isotropic liquid. In situ annealing experiments, by DSC, revealed the presence of an endotherm, unexplained by either a phase transition or solvent loss, and it is believed to be the result of a structural rearrangement that has no impact on the macroscopic properties of the material. Spray-dried cyclosporine at room temperature is therefore a frozen thermotropic liquid crystal due to the presence of two-dimensional order and the lack of substantial residual solvent. This is, to our knowledge, the first report of the existence of a thermotropic liquid crystal of a naturally occurring peptide.
Lechuga-Ballesteros
David
D
Nektar Therapeutics, 150 Industrial Road, San Carlos, California 94070-6256, USA. dlechuga@ca.nektar.com
Abdul-Fattah
Ahmad
A
Stevenson
Cynthia L
CL
Bennett
David B
DB
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000737:chemistry*; D004355:Drug Stability; D007166:Immunosuppressive Agents / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008859:Microscopy, Polarization / Q000379:methods; D015394:Molecular Structure; D013057:Spectrum Analysis / Q000379:methods; D013696:Temperature; D013818:Thermogravimetry / Q000379:methods; D014867:Water; D014961:X-Ray Diffraction / Q000379:methods
D007166:Immunosuppressive Agents; D014867:Water; D016572:Cyclosporine