Co-amorphous solids of dasatinib and olanzapine by saccharin with promising physicochemical properties

Two co-amorphous compounds of poorly water-soluble drugs dasatinib (DAS) and olanzapine (OLA) were formed, dasatinib-saccharin (DAS-SAC), and olanzapine-saccharin (OLA-SAC) with saccharin (SAC) as the co-former through liquid assisted grinding method, and at large scale, by rapidly evaporating the solvent (ethanol) from a rota-vapor at 60 °C under vacuum. The co-amorphous solids showed improved dissolution rates in phosphate-buffered saline (PBS, pH 7.2) and glycine-HCl buffer (pH 3.6) at 37 °C compared to the freeform. For example, the dissolution rate of DAS-SAC in PBS in first 10 min was 0.12 mg/mL (30-times faster than DAS) compared to 0.004 mg/mL of DAS. The dissolution rate of OLA-SAC in PBS in 10 min was 1.72 mg/mL and more than OLA (~21 times faster) as opposed to 0.08 mg/mL of OLA. Thermal analysis of the DAS-SAC and OLA-SAC showed single glass transition temperature (Tg) with the onsets of 132.8 °C and 161.7 °C, respectively indicating the amorphous nature of solids. The co-amorphous forms were stable at various temperatures (6 °C, 25 °C and 40 °C) and relative humidity (11%, 75% and dry condition) for up to eight weeks. Importantly, no amorphous forms were able to produce with DAS and OLA through grinding or quick evaporation without the use of SAC. Two co-amorphous solids of poorly water-soluble drugs dasatinib (DAS) and olanzapine (OLA) were successfully formed, dasatinib-saccharin (DAS-SAC), and olanzapine-saccharin (OLA-SAC). DAS-SAC and OLA-SAC showed improved dissolution rates (20-30 times faster) in phosphate-buffered saline (pH 7.2) at 37 °C than freeform drugs, and stable at high relative humidity (RH) stress (75% RH at 40°) up to 8 weeks. [Display omitted]