Coated tablets
Disclosed is a pharmaceutically acceptable oral dosage form comprising fenofibrate, phospholipid, a buffer salt, a water-soluble bulking agent selected from maltodextrin, mannitol, and combinations thereof, a cellulosic additive, beads or crystals of a pharmaceutically acceptable water-soluble excipient support material, a polyvinylpyrrolidone or crospovidone, croscarmellose sodium, granular mannitol, sodium dodecyl sulfate, silicon dioxide, and a stearate, wherein the fenofibrate is in the form of microparticles, and wherein at least a portion of the phospholipid is coated on the surfaces of the fenofibrate microparticles, the phospholipid coated microparticles are embedded in a matrix comprising the water-soluble bulking agent, phospholipid that is not coated on the microparticles, the buffer salt and the cellulosic additive, and the matrix is coated on up to 100% of the surfaces of the beads or crystals of the excipient support material.
1. A pharmaceutically acceptable oral dosage form of fenofibrate comprising fenofibrate present in an amount of from about 15% w/w to about 20% w/w of the dosage form;
phospholipid present in an amount of from about 1% w/w to about 8% w/w of the dosage form;
a buffer salt present in an amount of from about 0.1% w/w to about 0.5% w/w of the dosage forth;
one or more water-soluble bulking agent selected from maltodextrin and mannitol present in an amount of from about 7% w/w to about 20% w/w of the dosage form;
a cellulosic additive present in an amount of from about 3% w/w to about 8% w/w of the dosage form;
beads or crystals of a pharmaceutically acceptable water-soluble excipient support material present in an amount of from about 12% w/w to 16% w/w of the dosage form;
a polyvinylpyrrolidone or crospovidone present in an amount of from about 5% w/w to about 30% w/w of the dosage form;
croscarmellose sodium present in an amount of from about 1% w/w to about 6% w/w of the dosage form;
granular mannitol present in an amount of from about 3% w/w to about 30% w/w of the dosage form;
sodium dodecyl sulfate present in an amount of from about 1% w/w to about 4% of the dosage form;
silicon dioxide present in an amount of up to about 1% w/w of the dosage form; and
a stearate present in an amount of up to about 1% w/w of the dosage form;
wherein the fenofibrate is in the form of microparticles coated with phospholipid,
wherein the phospholipid coated microparticles are embedded in a matrix comprising the water-soluble bulking agent, phospholipid that is not coated on the microparticles, the buffer salt and the cellulosic additive, and
wherein the surface of the beads or crystals of the pharmaceutically acceptable water-soluble excipient is coated with the matrix.
2. The dosage form of claim 1 , wherein the fenofibrate is present in an amount of from about 18% w/w to about 19.5% w/w of the tablet.
3. The dosage form of claim 1 , wherein the phospholipid is present in an amount of from about 2% w/w to about 6% w/w of the tablet.
4. The dosage form of claim 1 , wherein the buffer salt is present in an amount of from 0.1% w/w to about 0.2% w/w of the tablet.
5. The dosage form of claim 1 , wherein the bulking agent is maltodextrin present in an amount of from about 9% w/w to about 20% w/w of the tablet.
6. The dosage form of claim 1 , wherein the bulking agent is mannitol present in an amount of from about 7% w/w to about 20% w/w of the tablet.
7. The dosage form of claim 1 , wherein the cellulosic additive is a carboxymethylcellulose.
8. The dosage form of claim 1 , wherein the cellulosic additive is sodium carboxymethylcellulose.
9. The dosage form of claim 1 , wherein the cellulosic additive is present in an amount of from about 4% w/w to about 6% w/w of the tablet.
10. The dosage form of claim 1 , wherein the water-soluble excipient support material present is present in an amount of from about 14% w/w to about 15% w/w of the tablet.
11. The dosage form of claim 1 , wherein the polyvinylpyrrolidone or crospovidone is present in an amount of from about 6% w/w to about 26% w/w of the tablet.
12. The dosage form of claim 1 , wherein the croscarmellose sodium is present in an amount of from about 2% w/w to about 5% w/w of the tablet.
13. The dosage form of claim 1 , wherein the granular mannitol is present in an amount of from about 5% w/w to about 27% w/w of the tablet.
14. The dosage form of claim 1 , wherein the sodium dodecyl sulfate is present in an amount of from about 2% w/w to about 3% w/w of the tablet.
15. The dosage form of claim 1 , wherein the silicon dioxide is colloidal silicon dioxide present in an amount of from about 0.5% w/w to about 0.8% w/w of the tablet.
16. The dosage form of claim 1 , wherein the stearate is magnesium stearate present in an amount of from about 0.2% w/w to about 0.5% w/w of the tablet.
17. A method of treating dislipidemia or dislipoproteinemia in a mammal comprising administering to said mammal a therapeutically effective oral dosage form of claim 1 .
18. The method of claim 17 , wherein the dosage form provides into the blood of said mammal in a fasted state a therapeutically effective amount of said fenofibrate that is at least 90% of the area under the curve (AUC) amount of the fenofibrate provided by the dosage form into the blood of said mammal in a fed state.
19. The dosage form of claim 1 , wherein fenofibrate is present in an amount of from 45 to 51 mg per tablet dosage form.
20. The dosage form of claim 19 , wherein fenofibrate is present in an amount of 48 mg per tablet dosage form.
21. The dosage form of claim 1 , wherein fenofibrate is present in an amount of from 135 to 155 mg per tablet dosage form.
22. The dosage form of claim 21 , wherein fenofibrate is present in an amount of 144 or 145 mg per tablet dosage form.
23. The dosage form of claim 1 , wherein fenofibrate is present in an amount of from 120 to 130 mg per tablet dosage form.
24. The dosage form of claim 1 , which is free of food effect.
25. A suspension of microparticles consisting of
9%-10% fenofibrate,
2.7%-3% Lipoid E80,
10%-19% sucrose, and
0%-5% sorbitol.
26. A powder comprising a lyophilized preparation of the suspension of claim 25 , wherein said lypophilized preparation has a moisture content of between 0.1% and 0.3%.
27. A pharmaceutically acceptable tablet dosage form comprising the powder of claim 26 , blended with 0.5% sucrose, 0.2% magnesium stearate, and 0.2% colloidal silica.