Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
1. A pharmaceutical formulation for the treatment of narcolepsy or a symptom thereof comprising:
an immediate release portion and a modified release portion, the modified release portion comprising gamma-hydroxybutyrate, and the immediate release portion comprising:
gamma-hydroxybutyrate;
povidone; and
microcrystalline cellulose,
wherein the formulation is designed to be administered orally only once nightly.
2. The pharmaceutical formulation of claim 1 , wherein the formulation comprises an amount of gamma-hydroxybutyrate equivalent to from 3.0 g to 12 g of sodium oxybate.
3. The pharmaceutical formulation of claim 1 , wherein the formulation comprises 3.33% povidone (w/w).
4. The pharmaceutical formulation of claim 1 , wherein the formulation comprises 11.75% microcrystalline cellulose (w/w).
5. The pharmaceutical formulation of claim 1 , wherein the formulation comprises hydrogenated vegetable oil.
6. The pharmaceutical formulation of claim 5 , wherein the formulation comprises 10.07% hydrogenated vegetable oil (w/w).
7. The pharmaceutical formulation of claim 1 , wherein the formulation comprises an acidifying agent.
8. The pharmaceutical formulation of claim 7 , wherein the acidifying agent comprises 1.2% to 15% (w/w) of the formulation.
9. The pharmaceutical formulation of claim 7 , wherein the acidifying agent comprises 1.2% to 10% (w/w) of the formulation.
10. The pharmaceutical formulation of claim 7 , wherein the acidifying agent comprises 1.2% to 5% (w/w) of the formulation.
11. The pharmaceutical formulation of claim 7 , wherein the acidifying agent comprises 1.6% to 3.2% (w/w) of the formulation.
12. The pharmaceutical formulation of claim 7 , wherein the acidifying agent comprises malic acid.
13. The pharmaceutical formulation of claim 12 , wherein the formulation comprises 1.58% malic acid (w/w).
14. The pharmaceutical formulation of claim 1 , wherein the formulation comprises carrageenan gum.
15. The pharmaceutical formulation of claim 14 , wherein the formulation comprises 1.05% carrageenan gum (w/w).
16. The pharmaceutical formulation of claim 1 , wherein the formulation comprises hydroxyethyl cellulose.
17. The pharmaceutical formulation of claim 16 , wherein the formulation comprises 1.05% hydroxyethyl cellulose (w/w).
18. The pharmaceutical formulation of claim 1 , wherein the formulation comprises carrageenan and hydroxyethyl cellulose in equal amounts.
19. The pharmaceutical formulation of claim 1 , wherein the formulation comprises xanthan gum.
20. The pharmaceutical formulation of claim 19 , wherein the formulation comprises 0.70% xanthan gum (w/w).
21. The pharmaceutical formulation of claim 1 , wherein the immediate release portion comprises 81% sodium oxybate (w/w).
22. The pharmaceutical formulation of claim 1 , wherein the immediate release portion comprises 15% microcrystalline cellulose (w/w).
23. The pharmaceutical formulation of claim 1 , wherein the formulation comprises one or more suspending or viscosifying agents.
24. The pharmaceutical formulation of claim 23 , wherein the one or more suspending or viscosifying agents comprises 1% to 15% (w/w) of the formulation.
25. The pharmaceutical formulation of claim 23 , wherein the one or more suspending or viscosifying agents comprises 2% to 10% (w/w) of the formulation.
26. The pharmaceutical formulation of claim 23 , wherein the one or more suspending or viscosifying agents comprises 2% to 5% (w/w) of the formulation.
27. The pharmaceutical formulation of claim 23 , wherein the one or more suspending or viscosifying agents comprises 2% to 3% (w/w) of the formulation.
28. The pharmaceutical formulation of claim 1 , wherein the modified release portion further comprises:
povidone;
microcrystalline cellulose;
hydrogenated vegetable oil;
methacrylic acid copolymer type C; and
methacrylic acid copolymer type B.
29. The pharmaceutical formulation of claim 1 , wherein the modified release portion further comprises:
povidone;
microcrystalline cellulose;
a polymer carrying free carboxylic groups; and
a hydrophobic compound having a melting point equal or greater than 40° C.