US2022257564A1PendingUtilityA1
Pharmaceutical compositions for treating cystic fibrosis
Est. expiryFeb 5, 2038(~11.6 yrs left)· nominal 20-yr term from priority
Inventors:Cathy ChuVarsha DhamankarEleni DokouEric L. HaseltineSamuel MoskowitzSarah RobertsonDavid WaltzWeichao George Chen
A61P 43/00A61K 9/2095A61K 31/47A61K 31/4045A61K 31/4439A61K 9/2027A61K 9/2054A61K 31/404A61P 11/00A61K 2300/00A61K 31/443A61P 25/28
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Claims
Abstract
A pharmaceutical composition comprising Compound I: Methods of treating cystic fibrosis comprising administering one or more of such pharmaceutical compositions to a patient.
Claims
exact text as granted — not AI-modified1 . A pharmaceutical composition comprising
(a) 75 mg to 125 mg of Compound I:
(b) a first solid dispersion comprising 25 mg to 75 mg of Compound II:
and 10 wt % to 30 wt % of a polymer relative to the total weight of the first solid dispersion; and
(c) a second solid dispersion comprising 50 mg to 100 mg of Compound III:
and 10 wt % to 30 wt % of a polymer relative to the total weight of the second solid dispersion.
2 . The pharmaceutical composition of claim 1 , comprising
75 mg to 125 mg of Compound I; and wherein the first solid dispersion comprises 50 mg of Compound II; and the second solid dispersion comprises 75 mg of Compound III.
3 . A pharmaceutical composition comprising:
(a) Compound I:
(b)
a first solid dispersion comprising 70 wt % to 90 wt % of Compound II relative to the total weight of the first solid dispersion:
and 10 wt % to 30 wt % of a polymer relative to the total weight of the first solid dispersion; and
(c)
a second solid dispersion comprising 70 wt % to 90 wt % of Compound III relative to the total weight of the second solid dispersion:
and 10 wt % to 30 wt % of a polymer relative to the total weight of the second solid dispersion, wherein the the weight ratio of Compound I in (a):Compound II in (b):Compound III in (c) is in a range of 4:2:3-6.
4 . (canceled)
5 . (canceled)
6 . (canceled)
7 . The pharmaceutical composition of claim 1 , wherein Compound I is Crystalline Form A.
8 . The pharmaceutical composition of claim 7 , wherein Compound I Crystalline Form A is in substantially pure form.
9 . The pharmaceutical composition of claim 7 , wherein Compound I Crystalline Form A is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 6.6±0.2, 7.6±0.2, 9.6±0.2, 12.4±0.2, 13.1±0.2, 15.2±0.2, 16.4±0.2, 18.2±0.2, and 18.6±0.2.
10 . A method of treating cystic fibrosis in a patient comprising orally administering to the patient one or more of the pharmaceutical composition of claim 1 .
11 . The method according to claim 10 , wherein said patient having cystic fibrosis is chosen from patients with F508del/minimal function genotypes, patients with F508del/F508del genotypes, patients with F508del/gating genotypes, and patients with F508del/residual function genotypes.
12 . (canceled)
13 . (canceled)
14 . The pharmaceutical composition of claim 3 , wherein at least one of the first and second solid dispersions is a spray-dried dispersion.
15 . The pharmaceutical composition of claim 3 , wherein both of the first and second solid dispersions are spray-dried dispersions.
16 . The pharmaceutical composition of claim 3 , wherein said polymer in the first solid dispersion is hydroxypropyl methylcellulose; and said polymer in the second solid dispersion is hydroxypropyl methylcellulose acetate succinate.
17 . The pharmaceutical composition of claim 3 , wherein:
the first solid dispersion comprises 70 wt % to 85 wt % of Compound II relative to the total weight of the first solid dispersion, and the polymer is hydroxypropyl methylcellulose in an amount of 15 wt % to 30 wt % relative to the total weight of the first solid dispersion; and the second solid dispersion comprises 70 wt % to 85 wt % of Compound III relative to the total weight of the second solid dispersion, 0.5% sodium lauryl sulfate relative to the total weight of the second solid dispersion, and the polymer is hydroxypropyl methylcellulose acetate succinate in an amount of 14.5 wt % to 29.5 wt % relative to the total weight of the second solid dispersion.
18 . The pharmaceutical composition of claim 3 , wherein the first solid dispersion comprises 80 wt % of Compound II relative to the total weight of the first solid dispersion; and 20 wt % of hydroxypropyl methylcellulose relative to the total weight of the first solid dispersion.
19 . The pharmaceutical composition of claim 3 , wherein the second solid dispersion comprises 80 wt % of Compound III relative to the total weight of the second solid dispersion; 0.5% of sodium lauryl sulfate relative to the total weight of the second solid dispersion, and 19.5 wt % of hydroxypropyl methylcellulose acetate succinate relative to the total weight of the second solid dispersion.
20 . The pharmaceutical composition of claim 3 , further comprising one or more pharmaceutically acceptable excipients chosen from one or more fillers, disintegrants, and lubricants.
21 . The pharmaceutical composition of claim 3 , wherein:
said fillers are chosen from microcrystalline cellulose, silicified microcrystalline cellulose, lactose, dicalcium phosphate, mannitol, copovidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methyl cellulose, ethyl cellulose, starch, Maltodextrin, agar, and guar gum; said disintegrants are chosen from croscarmellose sodium, sodium starch glycolate, crospovidone, corn or pre-gelatinized starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, and microcrystalline cellulose; and said lubricants are chosen from magnesium stearate, sodium stearyl fumarate, calcium stearate, sodium stearate, stearic acid, and talc.
22 . The pharmaceutical composition of claim 3 , wherein
Compound I is substantially crystalline, and wherein each of Compounds II and III is independently substantially amorphous.
23 . The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition is a tablet or in the form of granules.
24 . The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition further comprises microcrystalline cellulose; croscarmellose sodium; and
magnesium stearate.
25 . The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition comprises 15 wt % to 45 wt % of microcrystalline cellulose relative to the total weight of the pharmaceutical composition; 1 wt % to 10 wt % of croscarmellose sodium relative to the total weight of the pharmaceutical composition; and 0.5 wt % to 3 wt % mg of magnesium stearate relative to the total weight of the pharmaceutical composition.
26 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises 80 mg to 120 mg of Compound I.
27 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises 100 mg of Compound I; and wherein the first solid dispersion comprises 50 mg of Compound II; and the second solid dispersion comprises 75 mg of Compound III.
28 . A single tablet having the following formulation:
mg per
Material Name
tablet
Intra Granular
Compound I
100
Compound II SDD (80 wt %
62.5
Compound II and 20 wt %
HPMC)
Compound III SDD (80 wt %
93.8
Compound III, 19.5 wt %
HPMCAS, and 0.5 wt %
sodium lauryl sulfate)
Croscarmellose sodium
29.3
Microcrystalline cellulose
80.5
Extra Granular
Microcrystalline cellulose
117.1
Magnesium stearate
4.9
Total Core Tablet
488
Film coat
14.6
Total Coated Tablet
502.6.
29 . A single tablet having the following formulation:
mg per
Component
tablet
Intragranular
Compound I
50.0
a solid dispersion comprising:
31.3
80 wt % substantially amorphous
Compound II, and 20 wt % HPMC
a solid dispersion comprising:
46.9
80 wt % substantially amorphous
Compound III,
19.5 wt % HPMCAS, and
0.5 wt % sodium lauryl sulfate
Croscarmellose sodium
14.6
Microcrystaline cellulose
40.2
Extragranular
Microcrystaline cellulose
58.6
Magnesium stearate
2.4
Total Core Tablet
244.0
Film coat
7.3
Total
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