Pharmaceutical compositions
The present invention relates to the field of methods for providing pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to compositions comprising stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions and in therapy.
1. A method for the treatment of a leukemia, which comprises: administering to a patient in need thereof a therapeutically effective amount of a composition, comprising:
(a) particles comprising
(i) amorphous dasatinib; and
(ii) at least one polymeric stabilizing and matrix-forming component 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, DL lactide/glycolide copolymer, poly DL-lactide, cellulose acetate phthalate, carbomer homopolymer Type A, carbomer homopolymer Type B, an aminoalkyl methacrylate copolymer, and a poloxamer;
wherein the particles exclude at least one pharmaceutically acceptable solubilizer.
2. The method of claim 1 , wherein the dasatinib is present in an amount of from about 0.01% by weight to about 99.9% by weight of the particles.
3. The method of claim 1 , wherein the dasatinib is present in an amount of from about 30% by weight to about 99.9% by weight of the particles.
4. The method of claim 1 , wherein the dasatinib is present in an amount of from about 30% by weight to about 70% by weight of the particles.
5. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from polyvinylpyrrolidone, copolyvidone, and methacrylic acid and ethylacrylate copolymer.
6. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinylpyrrolidone, copolyvidone, methacrylic acid and ethylacrylate copolymer, methacrylate acid and methyl methacrylate copolymer, and an aminoalkyl methacrylate copolymer.
7. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from polyvinylpyrrolidone, copolyvidone, and hydroxypropyl methylcellulose.
8. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from polyvinylpyrrolidone, copolyvidone, and hydroxypropyl methylcellulose acetate succinate.
9. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from copolyvidone and methacrylic acid and ethylacrylate copolymer.
10. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from copolyvidone and methacrylate acid and methyl methacrylate copolymer.
11. The method of claim 1 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from copolyvidone and an aminoalkyl methacrylate copolymer.
12. The method of claim 1 , wherein the leukemia is at least one leukemia selected from a lymphocytic leukemia and a myelogenous leukemia.
13. The method of claim 1 , wherein the leukemia is at least one leukemia selected from an acute lymphocytic leukemia and an acute myelogenous leukemia.
14. The method of claim 1 , wherein the patient has a digestive pH of from about 1.2 to about 8.
15. The method of claim 1 , wherein the patient has a digestive pH of from about 4.5 to about 8.
16. A method for the treatment of a leukemia, which comprises: administering to a patient in need thereof a therapeutically effective amount of a tablet comprising:
(a) particles comprising
(i) amorphous dasatinib; and
(ii) at least one polymeric stabilizing and matrix-forming component 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, DL lactide/glycolide copolymer, poly DL-lactide, cellulose acetate phthalate, carbomer homopolymer Type A, carbomer homopolymer Type B, an aminoalkyl methacrylate copolymer, and a poloxamer;
wherein the particles exclude at least one pharmaceutically acceptable solubilizer; and
(b) an excipient.
17. The method of claim 16 , wherein the dasatinib is present in an amount of from about 0.01% by weight to about 99.9% by weight of the particles.
18. The method of claim 16 , wherein the dasatinib is present in an amount of from about 30% by weight to about 99.9% by weight of the particles.
19. The method of claim 16 , wherein the dasatinib is present in an amount of from about 30% by weight to about 70% by weight of the particles.
20. The method of claim 16 , wherein the leukemia is at least one leukemia selected from a lymphocytic leukemia and a myelogenous leukemia.
21. The method of claim 16 , wherein the leukemia is at least one leukemia selected from an acute lymphocytic leukemia and an acute myelogenous leukemia.
22. The method of claim 16 , wherein the patient has a digestive pH of from about 1.2 to about 8.
23. The method of claim 16 , wherein the patient has a digestive pH of from about 4.5 to about 8.
24. The method of claim 16 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinylpyrrolidone, copolyvidone, methacrylic acid and ethylacrylate copolymer, methacrylate acid and methyl methacrylate copolymer, and an aminoalkyl methacrylate copolymer.
25. The method of claim 16 , wherein the at least one polymeric stabilizing and matrix-forming component is selected from copolyvidone and methacrylic acid and ethylacrylate copolymer.
26. The method of claim 25 , wherein the dasatinib is present in an amount of from about 30% by weight to about 70% by weight of the particles.
27. The method of claim 25 , wherein the leukemia is at least one leukemia selected from a lymphocytic leukemia and a myelogenous leukemia.
28. The method of claim 25 , wherein the leukemia is at least one leukemia selected from an acute lymphocytic leukemia and an acute myelogenous leukemia.
29. The method of claim 25 , wherein the patient has a digestive pH of from about 1.2 to about 8.
30. The method of claim 25 , wherein the patient has a digestive pH of from about 4.5 to about 8.