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 hydroxypropyl methylcellulose acetate succinate (HPMC-AS);
wherein the cabozantinib and the hydroxypropyl methylcellulose acetate succinate are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:HPMC-AS).
2 . The amorphous solid dispersion of claim 1 , wherein the amorphous solid dispersion consists essentially of cabozantinib and HPMC-AS.
3 . The amorphous solid dispersion of claim 1 , wherein the amorphous solid dispersion consists of cabozantinib and HPMC-AS.
4 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is cabozantinib free base.
5 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is anhydrous cabozantinib free base.
6 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib is cabozantinib(S)-malate.
7 . The amorphous solid dispersion of claim 1 , wherein the cabozantinib and the HPMC-AS are present in a w/w ratio of 20:80 (cabozantinib:HPMC-AS).
8 . An amorphous solid dispersion consisting essentially of cabozantinib and hydroxypropyl methylcellulose acetate succinate (HPMC-AS);
wherein the cabozantinib and the hydroxypropyl methylcellulose acetate succinate are present in a w/w ratio of 20:80 (cabozantinib:HPMC-AS).
9 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib is cabozantinib free base.
10 . The amorphous solid dispersion of claim 8 , wherein the cabozantinib is anhydrous cabozantinib free base.
11 . The amorphous solid dispersion of claim 8 , wherein the amorphous solid dispersion consists of cabozantinib and HPMC-AS.
12 . The amorphous solid dispersion of claim 8 , wherein the amorphous solid dispersion consists of cabozantinib free base and HPMC-AS.
13 . The amorphous solid dispersion of claim 8 , wherein the amorphous solid dispersion consists of anhydrous cabozantinib free base and HPMC-AS.
14 . A pharmaceutical composition comprising an amorphous solid dispersion and one or more pharmaceutically acceptable additives;
wherein the amorphous solid dispersion comprises cabozantinib and hydroxypropyl methylcellulose acetate succinate (HPMC-AS); and
wherein the cabozantinib and the hydroxypropyl methylcellulose acetate succinate are present in a w/w ratio of 20:80 to 80:20 (cabozantinib:HPMC-AS).
15 . The pharmaceutical composition of claim 14 , wherein the amorphous solid dispersion consists essentially of cabozantinib and HPMC-AS.
16 . The pharmaceutical composition of claim 14 , wherein the amorphous solid dispersion consists of cabozantinib and HPMC-AS.
17 . The pharmaceutical composition of claim 14 , wherein the cabozantinib is cabozantinib free base.
18 . The pharmaceutical composition of claim 14 , wherein the cabozantinib is anhydrous cabozantinib free base.
19 . The pharmaceutical composition of claim 14 , wherein the cabozantinib and the HPMC-AS are present in a w/w ratio of 20:80 (cabozantinib:HPMC-AS).
20 . The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.