ABIRATERONE-CYCLIC OLIGOMER PHARMACEUTICAL FORMULATIONS AND METHODS OF FORMATION AND ADMINISTRATION THEREOF
The present disclosure relates to pharmaceutical formulations including abiraterone and a cyclic oligomer, as well as tablets including such pharmaceutical formulations, methods of forming such pharmaceutical formulations, and methods of administering such pharmaceutical formulations or tablets.
1 . A pharmaceutical formulation comprising:
abiraterone; and
a cyclic oligomer excipient.
2 . The pharmaceutical formulation of claim 1 , wherein the abiraterone and cyclic oligomer excipient are in an amorphous solid dispersion.
3 . The pharmaceutical formulation of claim 2 , wherein the amorphous solid dispersion contains less than 5% crystalline material.
4 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone.
5 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone, having the structural formula:
6 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone salt.
7 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone ester.
8 . The pharmaceutical formulation of claim 7 , wherein the abiraterone ester comprises abiraterone acetate, having the structural formula:
9 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone solvate.
10 . The pharmaceutical formulation of claim 1 , wherein the abiraterone comprises at least 99% abiraterone hydrate.
11 . The pharmaceutical formulation of claim 1 , comprising 10 mg, 25 mg, 50 mg, 70 mg, 75 mg, 100 mg, or 125 mg of amorphous abiraterone.
12 . The pharmaceutical formulation of claim 1 , comprising an amount of amorphous abiraterone sufficient to achieve the same or greater therapeutic effect, bioavailability, C min , C max or T max in a patient as 250 mg, 500 mg or 1000 mg of crystalline abiraterone or crystalline abiraterone acetate when consumed on an empty stomach.
13 . The pharmaceutical formulation of claim 1 , comprising 50 mg of amorphous abiraterone.
14 . The pharmaceutical formulation of claim 1 , comprising an amount of amorphous abiraterone sufficient to achieve the same or greater therapeutic effect, bioavailability, C min , C max or T max in a patient as 500 mg of crystalline abiraterone or crystalline abiraterone acetate when consumed on an empty stomach.
15 . The pharmaceutical formulation of claim 1 , comprising 50 mg or 70 mg of amorphous abiraterone.
16 . The pharmaceutical formulation of claim 1 , comprising an amount of amorphous abiraterone sufficient to achieve the same or greater therapeutic effect, bioavailability, C min , C max or T max in a patient as 500 mg or 1,000 mg of crystalline abiraterone or crystalline abiraterone acetate when consumed on an empty stomach.
17 . The pharmaceutical formulation of claim 1 , wherein the abiraterone and cyclic oligomer are present in a molar ratio of 1:0.25 to 1:25.
18 . The pharmaceutical formulation of claim 1 , wherein the abiraterone and cyclic oligomer are present in a molar ratio of at least 1:2.
19 . The pharmaceutical formulation of claim 1 , wherein the amorphous solid dispersion comprises 1% to 50% by weight abiraterone.
20 . The pharmaceutical formulation of claim 1 , wherein the amorphous solid dispersion comprises at least 10% by weight abiraterone.
21 . The pharmaceutical formulation of claim 1 , wherein the cyclic oligomer excipient comprises a cyclic oligosaccharide or cyclic oligosaccharide derivative.
22 . (canceled)
23 . The pharmaceutical formulation of claim 21 , wherein the cyclic oligosaccharide or cyclic oligosaccharide derivative comprises a hydroxy propyl β cyclodextrin.
24 . The pharmaceutical formulation of claim 21 , wherein the cyclic oligosaccharide or cyclic oligosaccharide derivative comprises a sodium (Na) sulfo-butyl ether β cyclodextrin.
25 - 26 . (canceled)
27 . The pharmaceutical formulation of claim 1 , wherein the amorphous solid dispersion comprises 50% to 99% by weight cyclic oligomer excipient.
28 . The pharmaceutical formulation of claim 1 , wherein the amorphous solid dispersion comprises at least 60% by weight cyclic oligomer excipient.
29 . The pharmaceutical formulation of claim 1 , wherein the amorphous solid dispersion comprises an additional excipient.
30 - 42 . (canceled)
43 . The pharmaceutical formulation of claim 1 , further comprising a glucocorticoid replacement API.
44 . (canceled)
45 . The pharmaceutical formulation of claim 1 , formulated as tablet for oral administration.
46 - 48 . (canceled)
49 . The pharmaceutical formulation of claim 45 , wherein
the tablet comprises an external phase comprising an additional amount of the cyclic oligomer excipient.
50 . (canceled)
51 . The pharmaceutical formulation of claim 45 , wherein the tablet comprises a concentration enhancing polymer.
52 . The pharmaceutical formulation of claim 51 , wherein the concentration enhancing polymer comprises a hydroxypropylmethyl cellulose acetate succinate.
53 . The pharmaceutical formulation of claim 45 , wherein the tablet comprises an external phase comprising at least one additional drug release modifying excipient.
54 - 55 . (canceled)
56 . A method of forming a pharmaceutical formulation, the method comprising compounding crystalline abiraterone and a cyclic oligomer excipient in a thermokinetic mixer at a temperature less than or equal to 200° C. for less than 300 seconds to form an amorphous solid dispersion of abiraterone and cyclic oligomer excipient.
57 - 61 . (canceled)
62 . A method of forming a pharmaceutical formulation, the method comprising melt processing crystalline abiraterone and a cyclic oligomer excipient to form an amorphous solid dispersion of abiraterone and the cyclic oligomer excipient in which the abiraterone is not substantially thermally degraded.
63 - 66 . (canceled)
67 . A method of forming a pharmaceutical formulation, the method comprising dissolving crystalline abiraterone and a cyclic oligomer excipient in a common organic solvent to form a dissolved mixture and spray drying the dissolved mixture to form an amorphous solid dispersion of abiraterone and cyclic oligomer excipient.
68 - 72 . (canceled)
73 . A method of treating prostate cancer, breast cancer, salivary cancer or an androgen sensitive cancer in a patient, the method comprising administering a pharmaceutical formulation of claim 1 to a patient having prostate cancer, breast cancer, salivary cancer or an androgen sensitive cancer.
74 - 115 . (canceled)