Niraparib formulations
The present invention relates to pharmaceutical tablet compositions comprising the compound niraparib as an active pharmaceutical ingredient, suitable for oral administration as well as to methods for their preparation. Also described herein are tablet compositions containing niraparib formed by the disclosed methods, and therapeutic uses of such tablet compositions for treating various disorders and conditions.
1. A pharmaceutical composition in the form of a tablet comprising the following components on a weight percentage basis:
(i) in an intragranular portion:
(a) 40-50% of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate monohydrate;
(b) 9-11% of a first diluent;
(c) 30-40% of a second diluent;
(d) 1-3% of a binder;
(e) 0.1-2% of a disintegrant;
(f) 2-4% of a glidant, adsorbent, or absorbent; and
(g) 0.1-2% of a lubricant; and
(ii) in an extragranular portion:
(a) 0.1-2% of a disintegrant;
(b) 0.1-2% of a glidant, adsorbent, or absorbent; and
(c) 0.1-2% of a lubricant.
2. The pharmaceutical composition according to claim 1 , wherein the first diluent is lactose monohydrate.
3. The pharmaceutical composition according to claim 1 , wherein the second diluent is microcrystalline cellulose.
4. The pharmaceutical composition according to claim 1 , wherein the binder is povidone.
5. The pharmaceutical composition according to claim 1 , wherein the intragranular disintegrant is crospovidone.
6. The pharmaceutical composition according to claim 1 , wherein the intragranular glidant, adsorbent, or absorbent is silicon dioxide.
7. The pharmaceutical composition according to claim 1 , wherein the intragranular lubricant is magnesium stearate.
8. The pharmaceutical composition according to claim 1 , wherein the extragranular phase disintegrant is crospovidone.
9. The pharmaceutical composition according to claim 1 , wherein the extragranular glidant, adsorbent, or absorbent is silicon dioxide.
10. The pharmaceutical composition according to claim 1 , wherein the extragranular lubricant is magnesium stearate.
11. The pharmaceutical composition according to claim 1 , wherein:
(i) the first diluent of the intragranular portion is lactose monohydrate;
(ii) the second diluent of the intragranular portion is microcrystalline cellulose;
(iii) the binder of the intragranular portion is povidone;
(iv) the disintegrant of the intragranular portion is crospovidone;
(v) the glidant, adsorbent, or absorbent of the intragranular portion is silicon dioxide;
(vi) the lubricant of the intragranular portion is magnesium stearate;
(vii) the disintegrant of the extragranular portion is crospovidone;
(viii) the glidant, adsorbent, or absorbent of the extragranular portion is silicon dioxide; and
(ix) the lubricant of the extragranular portion is magnesium stearate.
12. The pharmaceutical composition according to claim 1 , further comprising a film coating.
13. The pharmaceutical composition according to claim 1 , wherein the amount of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate monohydrate in the tablet is about 100 mg based on niraparib free base.
14. The pharmaceutical composition according to claim 1 , wherein the amount of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate monohydrate in the tablet is about 200 mg based on niraparib free base.
15. The pharmaceutical composition according to claim 1 , wherein the amount of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate monohydrate in the tablet is about 300 mg based on niraparib free base.