Galenical formulations of organic compounds
View Patent ↗The present invention relates to a solid oral dosage form comprising a therapeutically effective amount of aliskiren or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of HCTZ and a hydrophilic filler selected from the group a carbohydrate or combinations thereof, e.g. sugars, sugar alcohols and starches or combinations of these.
1. A solid oral dosage form comprising
(i) 28-44% aliskiren, or a pharmaceutically acceptable salt thereof, by weight based on the total weight of the oral dosage form;
(ii) 1.4-5.5% hydrochlorothiazide by weight based on the total weight of the oral dosage form; and
(iii) 5-25% carbohydrate hydrophilic filler by weight based on the total weight of the oral dosage form, wherein the carbohydrate hydrophilic filler is a mixture of wheat starch and lactose;
(iv) 22-33% microcrystalline cellulose, by weight based on the total weight of the oral dosage form;
(v) 9-13% crosslinked polyvinylpyrrolidone, by weight based on the total weight of the oral dosage form;
(vi) 0.6-1.8% colloidal silicon dioxide, by weight based on the total weight of the oral dosage form;
(vii) 0.4-1.8% talc, by weight based on the total weight of the oral dosage form;
(viii) 1-1.5% magnesium stearate, by weight based on the total weight of the oral dosage form; and
(ix) 2.1-3.2% polyvinylpyrrolidone, by weight based on the total weight of the oral dosage form.
2. The solid oral dosage form of claim 1 wherein aliskiren comprises about 75 to about 600 mg of the free base per unit dosage form.
3. The solid oral dosage form of claim 2 wherein aliskiren comprises about 83 mg per unit dosage form.
4. The solid oral dosage form of claim 2 wherein aliskiren comprises about 166 mg per unit dosage form.
5. The solid oral dosage form of claim 2 wherein aliskiren comprises about 332 mg per unit dosage form.
6. The solid oral dosage form of claim 1 wherein hydrochlorothiazide comprises about 12.5 to about 25 mg per unit dosage form.
7. The solid oral dosage form of claim 1 wherein the carbohydrate hydrophilic filler comprises about 30 to about 150 mg per unit dosage form.
8. The solid oral dosage form of claim 7 wherein the carbohydrate hydrophilic filler comprises about 50 to about 100 mg per unit dosage form.
9. The solid oral dosage form of claim 1 in the form of a film coated tablet.
10. The solid oral dosage form of claim 1 comprising
(i) 82.875 mg aliskiren hemifumarate;
(ii) 12.5 mg hydrochlorothiazide;
(iii) 25 mg lactose and 24.5 mg wheat starch;
(iv) 67.125 mg microcrystalline cellulose;
(v) 25.1 mg crosslinked polyvinylpyrrolidone;
(vi) 4.4 mg colloidal silicon dioxide;
(vii) 4.15 mg talc;
(viii) 3.35 mg magnesium stearate; and
(ix) 6 mg polyvinylpyrrolidone.
11. The solid oral dosage form of claim 1 comprising
(i) 165.75 mg aliskiren hemifumarate;
(ii) 25 mg hydrochlorothiazide;
(iii) 50 mg lactose and 49 mg wheat starch;
(iv) 134.25 mg microcrystalline cellulose;
(v) 50.2 mg crosslinked polyvinylpyrrolidone;
(vi) 8.8 mg colloidal silicon dioxide;
(vii) 8.3 mg talc;
(viii) 6.7 mg magnesium stearate; and
(ix) 12 mg polyvinylpyrrolidone.
12. The solid oral dosage form of claim 1 comprising
(i) 165.75 mg aliskiren hemifumarate;
(ii) 12.5 mg hydrochlorothiazide;
(iii) 25 mg lactose and 24.5 mg wheat starch;
(iv) 120.75 mg microcrystalline cellulose;
(v) 49.7 mg crosslinked polyvinylpyrrolidone;
(vi) 5.3 mg colloidal silicon dioxide;
(vii) 4.15 mg talc;
(viii) 5.35 mg magnesium stearate; and
(ix) 12 mg polyvinylpyrrolidone.
13. The solid oral dosage form of claim 1 comprising
(i) 331.5 mg aliskiren hemifumarate;
(ii) 25 mg hydrochlorothiazide;
(iii) 50 mg lactose and 49 mg wheat starch;
(iv) 241.5 mg microcrystalline cellulose;
(v) 99.4 mg crosslinked polyvinylpyrrolidone;
(vi) 10.6 mg colloidal silicon dioxide;
(vii) 8.3 mg talc;
(viii) 10.7 mg magnesium stearate; and
(ix) 24 mg polyvinylpyrrolidone.
14. The solid oral dosage form of claim 1 comprising
(i) 331.5 mg aliskiren hemifumarate;
(ii) 12.5 mg hydrochlorothiazide;
(iii) 25 mg lactose and 24.5 mg wheat starch;
(iv) 241.5 mg microcrystalline cellulose;
(v) 100.4 mg crosslinked polyvinylpyrrolidone;
(vi) 7.1 mg colloidal silicon dioxide;
(vii) 4.15 mg talc;
(viii) 9.35 mg magnesium stearate; and
(ix) 24 mg polyvinylpyrrolidone.