Pharmaceutical composition with improved bioavailability
The invention relates to solid dispersions of poorly water soluble compounds, in particular Compound A as disclosed herein, formed by solvent co-precipitation or spray drying, resulting in improved bioavailability, safety and tolerability of said compounds.
1. A physically stable solid dispersion comprising compound (A):
and a stabilizing polymer, wherein said stabilizing polymer is Poly(methacylic acid)-co-methyl methacrylate or Poly(vinylpyrrolidone-co-vinyl acetate)(6+4).
2. The solid dispersion of claim 1 , wherein the stabilizing polymer is Poly(methacylic acid)-co-methyl methacrylate.
3. The solid dispersion of claim 1 , wherein the stabilizing polymer is Poly(vinylpyrrolidone-co-vinyl acetate)(6+4).
4. The solid dispersion according to claim 1 wherein the ratio of the amount by weight of Compound A within the solid dispersion to the amount by weight of the stabilizing polymer therein is between 5:95 to 70:30.
5. A physically stable solid dispersion, comprising compound (A):
and a stabilizing polymer that is Poly(vinylpyrrolidone-co-vinyl acetate)(6+4), wherein the ratio of the amount by weight of Compound A in the solid dispersion to the amount by weight of the stabilizing polymer therein is between 5:95 to 70:30.
6. The solid dispersion of claim 4 wherein the ratio of the amount by weight of the Compound A within the solid dispersion to the amount by weight of the stabilizing polymer therein is 30:70 to 50:50.
7. The solid dispersion of claim 5 wherein the ratio of the amount by weight of the Compound A within the solid dispersion to the amount by weight of the stabilizing polymer therein is preferably 30:70 to 50:50.
8. The solid dispersion of claim 5 , wherein the solid dispersion is obtained by spray drying of a solution comprising Compound A and Poly(vinylpyrrolidone-co-vinyl acetate)(6+4).
9. The solid dispersion of claim 7 , wherein the solid dispersion is obtained by spray drying of a solution comprising Compound A and Poly(vinylpyrrolidone-co-vinyl acetate)(6+4).
10. A unit dose solid formulation comprising: the solid dispersion according to claim 1 , together with commonly used pharmaceutical ingredients selected from the group consisting of disintegrants, diluents, lubricants, and glidants together with a film coat.
11. A unit dose solid formulation comprising: the solid dispersion according to claim 5 , together with commonly used pharmaceutical ingredients selected from the group consisting of disintegrants, diluents, lubricants, and glidants together with a film coat.
12. A unit dose solid formulation, comprising approximately 80% of the solid dispersion according to claim 1 as an amorphous solid dispersion, together with about 7% croscarmellose sodium, about 6.8% mannitol, about 4% crospovidone, about 1.5% colloidal silicon dioxide and about 0.7% of magnesium stearate which is then encapsulated or compressed and coated as tablet.
13. A unit dose solid formulation, comprising approximately 80% of the solid dispersion according to claim 3 as an amorphous solid dispersion, together with about 7% croscarmellose sodium, about 6.8% mannitol, about 4% crospovidone, about 1.5% colloidal silicon dioxide and about 0.7% of magnesium stearate which is then encapsulated or compressed and coated as tablet.
14. A pharmaceutical preparation containing the solid dispersion according to claim 1 , together with additional pharmaceutically acceptable adjuvants.
15. A pharmaceutical preparation containing the solid dispersion according to claim 4 , together with additional pharmaceutically acceptable adjuvants.
16. A pharmaceutical preparation containing the solid dispersion according to claim 5 , together with additional pharmaceutically acceptable adjuvants.
17. A pharmaceutical preparation containing the solid dispersion according to claim 6 , together with additional pharmaceutically acceptable adjuvants.
18. A pharmaceutical preparation containing the solid dispersion according to claim 7 , together with additional pharmaceutically acceptable adjuvants.
19. A pharmaceutical preparation containing the solid dispersion according to claim 8 , together with additional pharmaceutically acceptable adjuvants.
20. A unit dose solid formulation comprising: the solid dispersion according to claim 7 , together with commonly used pharmaceutical ingredients selected from the group consisting of disintegrants, diluents, lubricants, and glidants together with a film.
21. A method of treating AML or prostate cancer, comprising the step of administering a therapeutically effective amount of the physically stable solid dispersion of claim 6 to a subject in need thereof.