Exploration of alternate
solid forms for dasatinib, a potent oncogene
tyrosine kinase inhibitor classified under Biopharmaceutics Classification
System (BCS) class II drugs with low water solubility and high permeability,
has been performed using COSMO-RS excess enthalpy (Hex) to increase
dissolution. The theoretical prediction resulted in the potential
for the formation of C
6
–C
8
fatty acid
solvates with dasatinib. A crystallization process has been identified
for the preparation of the predicted solvates and successfully scaled
up till the 100 g level. The fatty acid solvates are completely characterized
using powder X-ray diffraction (PXRD), differential scanning calorimetry
(DSC), thermogravimetric analysis (TGA), Fourier transform infrared
(FT-IR) spectroscopy, and proton nuclear magnetic resonance (
1
H NMR) spectroscopy. Unique powder X-ray diffraction patterns
and powder indexing of C
6
–C
8
fatty acid
solvates indicate the purity of the solid phase. The red shift in
the acid carbonyl stretching frequency of C
6
–C
8
fatty acids in FT-IR spectra and the intactness of the fatty
acid proton in
1
H-NMR spectra provide evidence for solvate
formation. The stoichiometry of active pharmaceutical ingredients
(APIs) with solvent in solvates is measured using TGA and
1
H-NMR spectroscopy. Dasatinib C
6
–C
8
fatty
acid solvates were found to retain their solid form under various
stress and pharmaceutical processing conditions. In addition, they
exhibited improved powder dissolution over dasatinib Form H1-7 by
2.2-fold. They also showed stability at 40 °C and 75% RH for
3 months. C
8
fatty acid is a USFDA GRAS listed solvent,
and hence may be a viable option for drug product development.