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 comprises amorphous abiraterone.
3 . The pharmaceutical formulation of claim 2 , wherein the abiraterone comprises less than 5% crystalline abiraterone.
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 . (canceled)
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 - 16 . (canceled)
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 . (canceled)
19 . The pharmaceutical formulation of claim 1 , comprising 1% to 50% by weight amorphous abiraterone.
20 . (canceled)
21 . The pharmaceutical formulation of claim 1 , wherein the cyclic oligomer excipient comprises a cyclic oligosaccharide or cyclic oligosaccharide derivative.
22 - 26 . (canceled)
27 . The pharmaceutical formulation of claim 1 comprising 50% to 99% by weight cyclic oligomer excipient.
28 . (canceled)
29 . The pharmaceutical formulation of Claim 1 further comprising an additional excipient.
30 - 42 . (canceled)
43 . The pharmaceutical formulation of claim 1 , further comprising a glucocorticoid replacement API.
44 - 57 . (canceled)
58 . A tablet for oral administration comprising any pharmaceutical formulation of claim 1 .
59 - 68 . (canceled)
69 . 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 abiraterone and a cyclic oligomer excipient.
70 - 74 . (canceled)
75 . A method of forming a pharmaceutical formulation, the method comprising hot-melt extrusion processing crystalline abiraterone and a cyclic oligomer excipient to form an amorphous abiraterone and the cyclic oligomer excipient in which the abiraterone is not substantially thermally degraded.
76 - 79 . (canceled)
80 . 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 abiraterone and cyclic oligomer excipient.
81 - 85 . (canceled)
86 . A method of forming a pharmaceutical formulation, the method comprising combining abiraterone and a cyclic oligomer excipient by a method comprising wet mass extrusion, high intensity mixing, high intensity mixing with a solvent, ball milling, or ball milling with a solvent to form an amorphous abiraterone and cyclic oligomer.
87 . A method of treating prostate cancer in a patient, the method comprising administering a pharmaceutical formulation of claim 1 to a patient having prostate cancer.
88 - 99 . (canceled)
100 . A method of treating breast cancer in a patient, the method comprising administering a pharmaceutical formulation of claim 1 to a patient having breast cancer.
101 - 110 . (canceled)
111 . A method of treating salivary gland cancer in a patient, the method comprising administering a pharmaceutical formulation of claim 1 to a patient having salivary gland cancer.
112 - 121 . (canceled)
122 . A method of treating cancer in a patient, the method comprising administering a pharmaceutical formulation of claim 1 to a patient having an androgen sensitive cancer.
123 - 131 . (canceled)
132 . The pharmaceutical formulation of claim 1 , comprising:
an inclusion complex comprising amorphous abiraterone and the cyclic oligomer excipient.
133 . The pharmaceutical formulation of claim 132 , wherein the pharmaceutical formulation comprises up to 30%, up to 20%, or up to 10% by weight amorphous abiraterone.
134 . (canceled)
135 . The pharmaceutical formulation of claim 132 , wherein the pharmaceutical formulation is formed by a method comprising thermokinetic compounding.
136 . The pharmaceutical formulation of claim 132 , wherein at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 99.9% of the amorphous abiraterone is present in the inclusion complex.
137 . The pharmaceutical formulation of claim 132 , wherein:
in response to heating the pharmaceutical formulation to a temperature up to 90% of the melting point of a crystalline form of abiraterone, and
allowing the pharmaceutical formulation to cool to room temperature, less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or 0.1% of the abiraterone is in crystalline form.
138 - 140 . (canceled)