Apalutamide (APA), a second-generation nonsteroidal antiandrogen BCS Class II drug with poor solubility and high permeability. A novel 1:1 cocrystal of Apalutamide (APA) with methylparaben (MP) was identified by cooling crystallization during the cocrystal screening and characterized by various solid-state techniques, such as PXRD, DSC, TGA, FT-IR, and 13C solid-state CP-MAS NMR spectroscopy. The crystal structures of APA and its cocrystal (APA-MP) were determined by the SC-XRD technique. The crystal structure analysis of the APA-MP cocrystal revealed that the APA and MP molecules are connected through strong O–H···O hydrogen bonds. The novel cocrystal improves the solubility and dissolution rate in different physiological conditions compared to poorly soluble APA due to strong hydrogen bond between the drug and the coformer. The cocrystal is stable (physically and chemically) under stress conditions, such as exposure to the relative humidity, mechanical grinding, open exposure to atmosphere at cRT (critical room temperature) and compression pressure of 10 tons. In addition, the compatibility of the cocrystal with excipients used in the drug product of APA (ERLEADA) was also investigated, and no disproportionation of cocrystal was observed.

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.