Amorphous cabozantinib particles and uses thereof
Amorphous solid dispersions of the protein kinase inhibitor cabozantinib. The amorphous solid dispersions exhibit chemical and physical stability under stressed conditions. The amorphous solid dispersions may be suitable for use in pharmaceutical compositions for administration to human subjects or patients.
1 . An amorphous solid dispersion comprising cabozantinib and one or more ionizable polymers;
wherein the cabozantinib and the one or more ionizable polymers are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:polymer).
2 . The amorphous solid dispersion of claim 1 , wherein the amorphous solid dispersion consists essentially of cabozantinib and the one or more ionizable polymers.
3 . The amorphous solid dispersion of claim 1 , wherein the one or more ionizable polymers includes at least one polymer that exhibits pH-dependent solubility.
4 . The amorphous solid dispersion of claim 1 , wherein the one or more ionizable polymers includes an anionic polymer.
5 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is cabozantinib free base.
6 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is anhydrous cabozantinib free base.
7 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is cabozantinib(S)-malate.
8 . An amorphous solid dispersion comprising cabozantinib and one or more ionizable polymers;
wherein the cabozantinib and the one or more ionizable polymers are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:polymer); and
wherein the one or more ionizable polymers includes an anionic polymer selected from the group consisting of: polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and methacrylic acid/ethyl acrylate copolymer.
9 . The amorphous solid dispersion of claim 8 , wherein the amorphous solid dispersion consists essentially of cabozantinib and the anionic polymer.
10 . The amorphous solid dispersion of claim 8 , wherein the amorphous solid dispersion consists of cabozantinib and the anionic polymer.
11 . The amorphous solid dispersion of claim 8 , wherein the one or more ionizable polymers includes at least one polymer that exhibits pH-dependent solubility.
12 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib and the one or more ionizable polymers are present in a w/w ratio of 50:50 (cabozantinib:polymer).
13 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib is cabozantinib free base.
14 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib is anhydrous cabozantinib free base.
15 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib is cabozantinib(S)-malate.
16 . An amorphous solid dispersion consisting essentially of cabozantinib and anionic polymer;
wherein the cabozantinib and the anionic polymer are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:polymer); and
wherein the anionic polymer is selected from the group consisting of: polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, methacrylic acid/ethyl acrylate copolymer, and combinations thereof.
17 . The amorphous solid dispersion of claim 16 , wherein the cabozantinib and the anionic polymer are present in a w/w ratio of 50:50 (cabozantinib:polymer).
18 . The amorphous solid dispersion of claim 16 , wherein the cabozantinib is cabozantinib free base.
19 . The amorphous solid dispersion of claim 16 , wherein the cabozantinib is anhydrous cabozantinib free base.
20 . The amorphous solid dispersion of claim 16 , wherein the cabozantinib is cabozantinib(S)-malate.
21 . A pharmaceutical composition comprising an amorphous solid dispersion and one or more pharmaceutically acceptable additives;
wherein the amorphous solid dispersion comprises cabozantinib and one or more ionizable polymers;
wherein the cabozantinib and the one or more ionizable polymers are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:polymer).
22 . The pharmaceutical composition of claim 21 , wherein the one or more ionizable polymers includes at least one polymer that exhibits pH-dependent solubility.
23 . The pharmaceutical composition of claim 21 , wherein the one or more ionizable polymers includes an anionic polymer.
24 . The pharmaceutical composition of claim 21 , wherein the one or more ionizable polymers includes an anionic polymer selected from the group consisting of: polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, and methacrylic acid/ethyl acrylate copolymer.
25 . The pharmaceutical composition of claim 21 , wherein the cabozantinib is cabozantinib free base.
26 . The pharmaceutical composition of claim 21 , wherein the cabozantinib is anhydrous cabozantinib free base.
27 . The pharmaceutical composition of claim 21 , wherein the cabozantinib is cabozantinib(S)-malate.
28 . The pharmaceutical composition of claim 21 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.