Drug delivery system to increase bioavailability
Drug delivery systems and compositions, comprising a glidant, that increase the bioavailability of biopharmaceutic class II, III, or IV active agents, and methods of making the same, are provided.
1. A drug delivery system comprising at least about 2 to about 40 weight percent of a glidant and a compound of Formula I:
or metabolites or pharmaceutically acceptable salts thereof.
2. The drug delivery system of claim 1 , wherein the glidant is silicon dioxide.
3. The drug delivery system of claim 2 further comprising:
sodium lauryl sulfate
polyethylene glycol;
lactose;
cellulose;
crospovidone;
copovidone;
a polyoxyethylene-polyoxypropylene copolymer;
and sodium stearyl fumarate or magnesium stearate.
4. The drug delivery system of claim 1 wherein the compound of Formula I is present in amount from 10 to 40 percent by weight.
5. The drug delivery system of claim 3 , wherein the sodium lauryl sulfate or polyethylene glycol is present in an amount from about 0.5 to about 3 percent or from about 2 to about 10 percent by weight, respectively.
6. The drug delivery system of claim 3 , wherein the polyethylene glycol is present in an amount from 2 to about 10 percent by weight.
7. The drug delivery system of claim 3 , wherein the lactose is present in an amount from about 5 to about 20 percent by weight.
8. The drug delivery system of claim 3 , wherein the cellulose is present in an amount from about 15 to about 60 percent by weight.
9. The drug delivery system of claim 3 , wherein the crospovidone is present in an amount from about 5 to about 20 percent by weight.
10. The drug delivery system of claim 3 , wherein the copovidone is present in an amount from about 0.2 to about 2 percent by weight.
11. The drug delivery system of claim 3 , wherein the polyoxyethylene-polyoxypropylene copolymer is present in an amount from about 2 to about 5 percent by weight.
12. The drug delivery system of claim 3 , wherein the sodium stearyl fumarate or magnesium stearate is present in an amount from about 0.5 to about 5 percent by weight.
13. A composition comprising the compound having Formula I
at least about 2 to about 40 weight percent silicon dioxide, and a pharmaceutically acceptable carrier.
14. The composition of claim 13 , wherein the bioavailability of the compound of Formula I is greater than 20.
15. The composition of claim 14 , wherein the bioavailability of the compound of Formula I is at least about 50.
16. A method of making a drug delivery system, comprising the steps of:
mixing a compound having Formula I
sodium lauryl sulphate or polyethylene glycol, and a polyoxyethylene-polyoxypropylene copolymer to form mixture I;
adding crospovidone or copovidone, lactose, cellulose, and a glidant to mixture I to form mixture II;
adding sodium stearyl fumarate to mixture II to form mixture III; and
compressing mixture III to form a tablet.
17. The method of claim 16 , wherein the glidant is silicone dioxide.
18. The method of claim 17 , wherein silicone dioxide is present in an amount from about 2 to about 15 percent.
19. The method of claim 18 , wherein the amount of silicone dioxide is about 7 to about 10 percent.
20. The method of claim 16 wherein the compound of Formula I is present in an amount from about 10 to 40 percent by weight, sodium lauryl sulphate or polyethylene glycol is present in an amount from about 0.5 to about 3 percent by weight, a polyoxyethylene-polyoxypropylene copolymer is present in an amount from about 2 to about 5 percent by weight, crospovidone is present in an amount from about 5 to about 20 percent, copovidone is present in an amount from about 0.2 to about 2 percent by weight, lactose is present in an amount from about 5 to about 20 percent by weight, cellulose is present in an amount from about 15 to about 60 percent by weight, and silicone dioxide is present in an amount from about 2 to about 15 percent.
21. The drug delivery system of claim 1 , further comprising 5 to 20 percent of the glidant.
22. The drug delivery system of claim 1 , further comprising 7 to 10 percent of the glidant.
23. The drug delivery system of claim 1 , further comprising 15 to 20 percent of the glidant.
24. The drug delivery system of claim 1 , further comprising 15 to 25 percent of the glidant.
25. The composition of claim 13 , further comprising 5 to 20 percent of silicon dioxide.
26. The composition of claim 13 , further comprising 7 to 10 percent of silicon dioxide.
27. The composition of claim 13 , further comprising 15 to 20 percent of silicon dioxide.
28. The composition of claim 13 , further comprising 15 to 25 percent of silicon dioxide.