Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds
The present invention is directed to processes for making and compositions containing quinolines such as formula I or pharmaceutically acceptable salts thereof wherein: X1 is H, Br, CI, or X2 is H, Br, CI, or n1 is 1-2; and n2 is 1-2.
1. A capsule pharmaceutical composition:
Ingredient
mg
/
unit
dose
total
fill
weight
×
100
Compound IB with 50 ppm or less
10
of 6,7-dimethoxy-quinoline-4-ol
(10 percent drug load formulation)
Silicified Microcrystalline Cellulose
78.7
Croscarmellose sodium
5
Sodium starch glycolate
5
Fumed Silica
0.3
Stearic acid
1
Total
100
wherein compound IB has the structure:
2. The capsule pharmaceutical composition of claim 1 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 25 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
3. The capsule pharmaceutical composition of claim 1 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 15 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
4. The capsule pharmaceutical composition of claim 1 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 10 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
5. A capsule pharmaceutical composition:
Ingredient
mg
/
unit
dose
total
fill
weight
×
100
Compound IB with 50 ppm or less
50
of 6,7-dimethoxy-quinoline-4-ol
(50 percent drug load formulation)
Silicified Microcrystalline Cellulose
37.7
Croscarmellose sodium
5
Sodium starch glycolate
5
Fumed Silica
0.3
Stearic acid
2
Total
100
wherein compound IB has the structure:
6. The capsule pharmaceutical composition of claim 5 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 25 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
7. The capsule pharmaceutical composition of claim 5 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 15 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
8. The capsule pharmaceutical composition of claim 5 , wherein the formation of 6,7-dimethoxy-quinoline-4-ol in the pharmaceutical composition is minimized to 10 ppm or less from 0 to 6 months at 25° C. and 60 percent relative humidity.
9. The capsule pharmaceutical composition of claim 1 containing 25 mg of Compound IB.
10. The capsule pharmaceutical composition of claim 9 containing:
Ingredient
mg/unit dose
Silicified Microcrystalline Cellulose
196.75
Croscarmellose sodium
12.5
Sodium starch glycolate
12.5
Fumed Silica
0.75
Stearic acid
2.5.
11. The capsule pharmaceutical composition of claim 5 containing 100 mg of Compound IB.
12. The capsule pharmaceutical composition of claim 11 containing:
Ingredient
mg/unit dose
Silicified Microcrystalline Cellulose
75.40
Croscarmellose sodium
10.00
Sodium starch glycolate
10.00
Fumed Silica
0.6
Stearic acid
4.0.