Formulations of Cabozantinib
View Patent ↗This document relates to compositions comprising a non-covalently bound complex comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000. This document also relates to compositions comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000. This document also relates to compositions consisting essentially of cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000.
1. A composition comprising a non-covalently bound complex comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:100 to about 1:2000, and wherein the composition is a clear aqueous solution when the composition is dissolved in an aqueous solution.
2. The composition of claim 1 , wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:150 to about 1:300.
3. A composition comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:100 to about 1:2000, and wherein the composition is a clear aqueous solution when the composition is dissolved in an aqueous solution.
4. The composition of claim 3 , wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:130 to about 1:500.
5. The composition of claim 3 , wherein the composition is a solid formulation.
6. The composition of claim 3 , wherein the composition is an aqueous formulation.
7. The composition of claim 3 , wherein the composition is a clear aqueous solution for at least 2 hours, when the composition is dissolved in an aqueous solution.
8. The composition of claim 3 , wherein the composition has pH value from about 5 to about 8.
9. The composition of claim 6 , wherein after the aqueous formulation is filtered by a 0.22 micron filter, the amount of cabozantinib in the filtered aqueous solution is at least 96% of the total amount of cabozantinib in the aqueous solution before the filtration.
10. The composition of claim 6 , wherein after the aqueous formulation is filtered by a 0.22 micron filter, the amount of cabozantinib in the filtered aqueous solution is at least 97% of the total amount of cabozantinib in the aqueous solution before the filtration.
11. The composition of claim 3 , produced by a method comprising the steps of:
(i) obtaining an organic solution of cabozantinib in a polar water-miscible organic solvent;
(ii) obtaining a first aqueous solution of human serum albumin; and
(iii) mixing the organic solution of cabozantinib and the first aqueous solution of human serum albumin to obtain a second aqueous solution comprising the composition comprising cabozantinib and human serum albumin.
12. The composition of claim 11 , wherein the composition comprises a non-covalently bound complex comprising cabozantinib and human serum albumin.
13. The composition of claim 11 , wherein the polar water-miscible organic solvent is ethanol.
14. The composition of claim 11 , wherein the composition is prepared by further comprising removing the organic solvent and the aqueous solvent from the second aqueous solution to obtain the composition comprising cabozantinib and human serum albumin, and the removing is carried out by lyophilization.
15. The composition of claim 11 , wherein the composition forms a clear aqueous solution when the composition is dissolved in an aqueous solvent, and wherein the solubility of the composition in the aqueous solution is at least 10 mg/ml.
16. The composition of claim 11 , wherein the amount of aqueous solvent in the first aqueous solution is from about 0.008 mL to about 0.05 mL per 1 mg of human serum albumin.