Co-crystals, method and apparatus for forming the same
AssigneeThe Regents of the University of Michigan
InventorsMax Shtein, Siddharth Borsadia, Eugene Shteyn
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Abstract
Disclosed herein is a method and apparatus for synthesizing co-crystals from the vapor phase without the need for liquid solvent. Also disclosed herein are co-crystals formed from the vapor phase, substrates coated with said co-crystals, pharmaceutical compositions thereof and apparatuses for producing said co-crystals.
Claims20
A method of forming a co-crystal of an organic compound and a coformer comprising:
- (a) subliming and/or evaporating the organic compound optionally in the presence of an organic compound carrier gas to form an organic compound vapor;
- (b) subliming and/or evaporating the coformer optionally in the presence of a coformer carrier gas to form a coformer vapor;
- (c) mixing the organic compound vapor and the coformer vapor, optionally in the presence of a mixing gas, to form a vapor mixture, wherein the vapor mixture comprises a molar ratio of the organic compound and the coformer of 10:1 to 1:10;
- and
- (d) condensing the vapor mixture onto a substrate to form the co-crystal;
- wherein:
- the co-crystal comprises the organic compound and the coformer hydrogen bonded together, optionally in a ratio of 1:3 to 3:1;
- the organic compound is sublimed at a temperature that is 10° C. to 100° C. above its onset of sublimation, as determined by thermogravimetric analysis (“TGA”);
- the substrate is at a temperature of −50° C. to 50° C.;
- and the co-crystal is stable at 25° C., characterized by differential scanning calorimetry, microscopy, X-ray diffraction, or a combination thereof.
A co-crystal comprising caffeine and succinic acid, characterized by an X-ray diffraction (“XRD”) pattern comprising peaks at 14, 18, and 22±0.2° 2θ using Cu Kα radiation.
An apparatus for producing a co-crystal comprising
- a housing having
- (i) a vapor mixing chamber adjacent to a jet exiting nozzle end of the housing;
- and
- (ii) a receiving end opposite the jet exiting nozzle end;
- the vapor mixing chamber being adjacent to a temperature control shroud for controlling the temperature of a vapor mixture of the organic compound and the coformer in the vapor mixing chamber;
- a first tubular internal container for injecting an organic compound and positioned within the receiving end, having
- (i) an outlet nozzle for feeding the organic compound into the vapor mixing chamber;
- (ii) an organic compound carrier gas inlet tube;
- and
- (iii) a thermocouple at a proximal end for controlling evaporation temperature of the first tubular internal container;
- and
- a second tubular internal container for injecting the coformer and positioned within the receiving end, having
- (i) an outlet nozzle for feeding the coformer into the vapor mixing chamber,
- (ii) a coformer carrier gas inlet tube, and
- (iii) a thermocouple at a proximal end for controlling evaporation temperature of the second tubular internal container,
- wherein at least one of the first tubular container and the second tubular container has a mixing gas inlet.
Dependencies are inferred from the claim text.