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Preformulation studies of dovitinib free base: Solubility, lipophilicity and stability

Dovitinib has been investigated as an anti-tumor drug due to its ability to inhibit multiple receptor tyrosine kinases. Dovitinib free base has a poor water solubility leading to poor absorption. Salts and lipid-based formulations have been used to improve drug availability. Here, we investigated the physiochemical properties of the dovitinib free base in the presence of some pharmaceutical excipients. We sought to study the effect of acidic counterions on the aqueous solubility and lipophilicity of dovitinib and how pH, buffer species, and cyclodextrin (CD) influenced dovitinib stability. pH-solubility studies were performed by titration against five different acids. Aqueous solubility of dovitinib salt depended on the counterion. Lactic acid greatly increased the aqueous solubility of dovitinib. The counterion effect on the solubility was also investigated in the aqueous complexing media. Unexpected synergistic solubilization was found with γ-CD/phosphoric acid and γ-CD/maleic acid. The counterion did not affect the lipophilicity of dovitinib at physiological pH. Accelerated degradation of dovitinib was carried out at high temperature. Stability was studied across a range of pH values, buffer species and in the presence of two CDs. Dovitinib was most stable at pH 4 in the phosphate buffer species. γ-CD stabilized the drug at relatively low pH.

Related Products

Cat.No. Product Name Information
S1018 Dovitinib (TKI-258) Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

Related Targets

VEGFR c-Kit PDGFR FGFR FLT3