US2020338063A1PendingUtilityA1
Pharmaceutical compositions for the treatment of cftr mediated diseases
Est. expiryNov 2, 2032(~6.3 yrs left)· nominal 20-yr term from priority
A61K 45/06A61K 31/47A61K 31/443A61K 9/2095A61K 9/1605A61P 11/00A61P 3/12A61P 1/18A61P 1/00A61K 9/2077A61K 9/2054A61K 9/2027A61K 9/2013A61K 9/2004A61K 9/14A61K 9/10A61K 9/0053A61K 9/20A61P 43/00A61P 1/16
68
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Pharmaceutical compositions comprising 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) in Form I and a solid dispersion comprising substantially amorphous N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (Compound 2), methods of treating, lessening the severity of, or symptomatically treating CFTR mediated diseases, such as cystic fibrosis, methods of manufacturing, methods of administering, and kits thereof are disclosed.
Claims
exact text as granted — not AI-modified1 - 48 . (canceled)
49 . A pharmaceutical composition comprising 200 mg of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I and a solid dispersion comprising 125 mg of substantially amorphous N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (Compound 2).
50 . The pharmaceutical composition of claim 49 , wherein the pharmaceutical composition is a tablet.
51 . The tablet of claim 50 , wherein the tablet comprises 25 to 50 percent by weight of Compound 1 Form I, and 15 to 35 percent by weight solid dispersion comprising substantially amorphous Compound 2.
52 . The tablet of claim 51 , further comprising:
microcrystalline cellulose, in an amount of 20 to 30 percent by weight; croscarmellose sodium, in an amount of 3 to 10 percent by weight; sodium lauryl sulfate, in an amount of 0.5 to 2 percent by weight; polyvinylpyrrolidone, in an amount of 0 to 5 percent by weight; magnesium stearate, in an amount of 0.5 to 2 percent by weight; and optionally further comprises a colorant and a wax.
53 . The tablet of claim 52 , having a formulation selected from:
% by wgt.
Compound 1 Form I
35
Solid dispersion comprising
28
substantially amorphous
Compound 2
Microcrystalline cellulose
26
Croscarmellose sodium
6
Sodium lauryl sulfate
1
Polyvinylpyrrolidone
3
Magnesium stearate
1;
mg
Compound 1 Form I
200
Solid dispersion comprising
156
substantially amorphous
Compound 2
Microcrystalline cellulose
150
Croscarmellose sodium
34
Sodium lauryl sulfate
4
Polyvinylpyrrolidone
15
Magnesium stearate
6;
% by wgt.
Compound 1 Form I
34
Solid dispersion comprising
27
substantially amorphous
Compound 2
Microcrystalline cellulose
25
Croscarmellose sodium
6
Sodium lauryl sulfate
1
Polyvinylpyrrolidone
3
Magnesium stearate
1
Colorant
3;
mg
Compound 1 Form I
200
Solid dispersion comprising
156
substantially amorphous
Compound 2
Microcrystalline cellulose
150
Croscarmellose sodium
34
Sodium lauryl sulfate
4
Polyvinylpyrrolidone
15
Magnesium stearate
6
Colorant
17;
and
mg
Compound 1 Form I
200
Substantially amorphous
125
Compound 2
Microcrystalline cellulose
150
Croscarmellose sodium
34
Sodium lauryl sulfate
4
Polyvinylpyrrolidone
15
Magnesium stearate
6
Colorant
17.
54 . A tablet comprising a fixed dosage amount of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I and a solid dispersion comprising substantially amorphous N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (Compound 2),
wherein the tablet comprises 25 to 50 percent by weight Compound 1 Form I and 15 to 35 percent by weight a solid dispersion comprising substantially amorphous Compound 2.
55 . The tablet of claim 54 , wherein the composition further comprises:
microcrystalline cellulose, in an amount of 20 to 30 percent by weight; croscarmellose sodium, in an amount of 3 to 10 percent by weight; sodium lauryl sulfate, in an amount of 0.5 to 2 percent by weight; polyvinylpyrrolidone, in an amount of 0 to 5 percent by weight; magnesium stearate, in an amount of 0.5 to 2 percent by weight; and optionally comprises a colorant and a wax.
56 . A pharmaceutical composition comprising:
a) about 100 mg of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I and about 125 mg of substantially amorphous N-(5-hydroxy-2,4-di-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (Compound 2); b) about 150 mg of Compound 1 Form I and about 200 mg of substantially amorphous Compound 2; or c) about 75 mg of Compound 1 Form I and about 100 mg of substantially amorphous Compound 2.
57 . The pharmaceutical composition of claim 56 , wherein the pharmaceutical composition comprises 100 mg of Compound 1 Form I and 125 mg of substantially amorphous Compound 2.
58 . The pharmaceutical composition of claim 57 , wherein the pharmaceutical composition is a tablet.
59 . The pharmaceutical composition of claim 48 , wherein the pharmaceutical composition comprises at least 20 percent by weight Compound 1 Form I, and at least 20 percent by weight substantially amorphous Compound 2.
60 . The pharmaceutical composition of claim 59 , further comprising:
microcrystalline cellulose, in an amount of 20 to 30 percent by weight; croscarmellose sodium, in an amount of 3 to 10 percent by weight; sodium lauryl sulfate, in an amount of 0.5 to 2 percent by weight; polyvinylpyrrolidone, in an amount of 0 to 5 percent by weight; and magnesium stearate, in an amount of 0.5 to 2 percent by weight.
61 . The pharmaceutical composition of claim 59 , having the following formulation:
Component
% by wgt.
Compound 1 Form I
20-40
Solid dispersion comprising
30-40
substantially amorphous
Compound 2
Microcrystalline cellulose
20-30
Croscarmellose sodium
1-10
Polyvinylpyrrolidone
1-5
Sodium lauryl sulfate
0.1-1
Magnesium stearate
0.5-1.5.
62 . The pharmaceutical composition of claim 61 , having the following formulation:
25% of Compound 1 Form I, by weight of the composition; 38% of a solid dispersion comprising substantially amorphous Compound 2, by weight of the composition; 26% of microcrystalline cellulose, by weight of the composition; 6% of croscarmellose sodium, by weight of the composition; 1% of sodium lauryl sulfate, by weight of the composition; and 3% of polyvinylpyrrolidone, by weight of the composition.
63 . The pharmaceutical composition of claim 57 , having the following formulation:
Component
mg/Tablet
Compound 1 Form I
100
Solid dispersion comprising
156
substantially amorphous
Compound 2
Microcrystalline cellulose
108
Croscarmellose sodium
25
Polyvinylpyrrolidone
11
Sodium lauryl sulfate
3
Magnesium stearate
4.
64 . The pharmaceutical composition of claim 56 , wherein the pharmaceutical composition is a granular pharmaceutical composition.
65 . The pharmaceutical composition of claim 64 , further comprising:
microcrystalline cellulose, in an amount of 10 to 20 percent by weight; croscarmellose sodium, in an amount of 1 to 3 percent by weight; sodium lauryl sulfate, in an amount of 0.5 to 2 percent by weight; and polyvinylpyrrolidone, in an amount of 0 to 5 percent by weight.
66 . The pharmaceutical composition of claim 65 , having the following formulation:
Component
% by wgt.
Compound 1 Form I
30
Solid dispersion comprising
47
substantially amorphous
Compound 2
Microcrystalline cellulose
17
Croscarmellose sodium
2
Polyvinylpyrrolidone
3
Sodium lauryl sulfate
1.
67 . A method of treating, lessening the severity of, or symptomatically treating cystic fibrosis in a patient comprising administering to the patient 800 mg of Compound 1 Form I and 500 mg of substantially amorphous Compound 2 daily.
68 . The method of claim 57 , wherein the method comprises administering 400 mg of Compound 1 Form I and 250 mg of substantially amorphous Compound 2 every 12 hours.
69 . The method of claim 68 , wherein the method comprises administering two dosage unit forms, each containing 200 mg of Compound 1 Form I and 125 mg of substantially amorphous Compound 2.
70 . A method of treating, lessening the severity of, or symptomatically treating cystic fibrosis in a patient comprising administering to the patient 400 mg of Compound 1 Form I and 500 mg of substantially amorphous Compound 2 daily.
71 . The method of claim 70 , wherein the method comprises administering 200 mg of Compound 1 Form I and 250 mg of substantially amorphous Compound 2 every 12 hours.
72 . The method of claim 71 , wherein the method comprises administering two dosage unit forms, each containing 100 mg of Compound 1 Form I and 125 mg of substantially amorphous Compound 2.
73 . A method of preparing a pharmaceutical composition, comprising wet granulating the following components:
a. Compound 1 Form I; b. a solid dispersion comprising substantially amorphous Compound 2; c. a filler; d. a disintegrant; e. a surfactant; and f. a binder.
74 . A method of preparing a tablet, comprising compressing the following components:
i) a plurality of granules produced by the method of claim 25 ; ii) a disintegrant; iii) a filler; and iv) a lubricant.
75 . A process for preparing a tablet comprising:
a) mixing Compound 1 Form I, a solid dispersion comprising substantially amorphous Compound 2, a filler, and a disintegrant in a blender to form a blend; b) preparing a granulation solution with water, a binder, and a surfactant; c) feeding the blend from step a) into a continuous twin screw granulator while adding the granulation solution from step b) to produce granules; d) drying the granules from step c) and milling them; e) blending the milled granules from step d) with a filler, disintegrant, and lubricant to form a blend; and f) compressing the blend from step e) into a tablet.Join the waitlist — get patent alerts
Track US2020338063A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.