Pharmaceutical compositions

1. A pharmaceutical composition, comprising:

(a) amorphous solid dispersion particles having a degree of amorphicity of 100%, wherein the particles consist of

(i) a protein kinase inhibitor in an amount of from about 10% by weight to about 70% by weight of the particles; and

(ii) at least one polymeric stabilizing and matrix-forming component;

wherein the amorphous solid dispersion particles are obtained by mixing i) a pressurized solution comprised of the protein kinase inhibitor and a solvent and ii) a pressurized antisolvent;

and

(b) optionally at least one pharmaceutically acceptable solubilizer selected from the group consisting of a d-α-tocopherol acid polyethylene glycol 1000 succinate, a PEG-40 hydrogenated castor oil, a PEG-35 castor oil, a PEG-40 stearate, a hard fat, a polyoxylglyceride, a PEG-8 caprylic/capric glyceride, and a poloxamer;

wherein the protein kinase inhibitor is sorafenib, a pharmaceutically acceptable salt, a hydrate, a solvate, or combinations thereof; and

wherein the at least one pharmaceutically acceptable solubilizer, when present, is a physical mixture with the amorphous solid dispersion particles.

2. The composition of claim 1 , wherein the amount of the protein kinase inhibitor is from about 10% by weight to about 50% by weight of the particles.

3. The composition of claim 1 , wherein the amount of the protein kinase inhibitor is from about 10% by weight to about 40% by weight of the particles.

4. The composition of claim 1 , wherein the amount of the protein kinase inhibitor is from about 10% by weight to about 30% by weight of the particles.

5. The composition of claim 1 , wherein the protein kinase inhibitor is sorafenib.

6. The composition of claim 1 , wherein the protein kinase inhibitor is sorafenib tosylate.

7. The composition of claim 1 , wherein the at least one protein kinase inhibitor is sorafenib hydrate.

8. The composition of claim 1 , wherein the at least one protein kinase inhibitor is sorafenib solvate.

9. The composition of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinylpyrrolidone, polyvinyl acetate phthalate, copolyvidone, crospovidone, methacrylic acid and ethylacrylate copolymer, methacrylate acid and methyl methacrylate copolymer, polyethylene glycol, DL lactide/glycolide copolymer, poly DL-lactide, cellulose acetate phthalate, carbomer homopolymer Type A, carbomer homopolymer Type B, aminoalkyl methacrylate copolymers, and poloxamers.

10. The composition of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from the group consisting of hydroxypropyl methylcellulose phthalate, hydroxypropyl cellulose, copolyvidone, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate and polyvinylpyrrolidone.

11. The composition of claim 1 , wherein the composition further comprises at least one pharmaceutically acceptable solubilizer.

12. The composition of claim 11 , wherein the solubilizer is d-α-tocopherol acid polyethylene glycol 1000 succinate.

13. The composition of claim 11 , wherein the solubilizer is distributed to the surface of the particles.

14. The composition of claim 1 , wherein the particles have an average particle diameter size of less than: (i) about 1000 nm, (ii) about 500 nm, or (iii) about 250 nm.

15. The pharmaceutical composition of claim 1 ,

wherein the protein kinase inhibitor is sorafenib or sorafenib tosylate;

wherein the at least one polymeric stabilizing and matrix-forming component is hydroxypropyl methylcellulose phthalate; and

wherein at least one pharmaceutically acceptable solubilizer is d-α-tocopherol acid polyethylene glycol 1000 succinate.

16. The pharmaceutical composition of claim 15 , wherein the amount of sorafenib, based on the total weight of particles, is from about 10% by weight to about 40% by weight.

17. The pharmaceutical composition of claim 15 , wherein the particles have an average particle size of less than: (i) about 1000 nm, (ii) about 500 nm, or (iii) about 250 nm.

18. The pharmaceutical composition of claim 15 , wherein the amount of sorafenib, based on the total weight of particles, is from about 10% by weight to about 30% by weight.

19. The pharmaceutical composition of claim 1 , wherein the pressurized antisolvent comprises carbon dioxide.

20. A method of treating a proliferative disorder in a patient in need thereof, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 1 .

21. The method of claim 20 , wherein the proliferative disorder is selected from tumours and cancers.

22. The method of claim 20 , wherein the proliferative disorder is selected from neurofibromatosis, tuberous sclerosis, hemangiomas and lymphangiogenesis, cervical, anal and oral cancers, eye or ocular cancer, stomach cancer, colon cancer, bladder cancer, rectal cancer, liver cancer, pancreas cancer, lung cancer, breast cancer, cervix uteri cancer, corpus uteri cancer, ovary cancer, prostate cancer, testis cancer, renal cancer, brain cancer, cancer of the central nervous system, head and neck cancer, throat cancer, skin melanoma, acute lymphocytic leukemia, acute myelogenous leukemia, Ewing's Sarcoma, Kaposi's Sarcoma, basal cell carcinoma and squamous cell carcinoma, small cell lung cancer, choriocarcinoma, rhabdomyosarcoma, angiosarcoma, hemangioendothelioma, Wilms Tumor, neuroblastoma, mouth/pharynx cancer, esophageal cancer, larynx cancer, lymphoma, multiple myeloma; cardiac hypertrophy, age-related macular degeneration and diabetic retinopathy.

23. A method of treating proliferative disorder in a patient in need thereof, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 15 .