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 method of treating narcolepsy or at least one symptom thereof, the method comprising:
opening a sachet containing a pharmaceutical composition;
orally administering the composition to a human subject in need thereof, wherein the orally administering occurs only once per night;
releasing gamma-hydroxybutyrate into the blood stream of the human subject as a result of the orally administering; and
inducing the human subject to sleep for at least six consecutive hours as a result of the orally administering and releasing.
2 . The method of claim 1 , wherein, when the orally administering comprises administering to the human subject a dose of the composition equivalent to 4.5 g or 6.0 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in FIG. 12 for the corresponding dose.
3 . The method of claim 1 , wherein, when the orally administering comprises administering to the human subject a dose of the composition equivalent to 4.5 g, 6.0 g, or 7.5 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in FIG. 13 for the corresponding dose.
4 . The method of claim 1 , wherein, when the orally administering comprises administering to the human subject a dose of the composition equivalent to 4.5 g, 7.5 g, or 9.0 g of sodium oxybate, the composition yields a plasma concentration versus time curve bioequivalent to the plasma concentration versus time curve depicted in FIG. 90 for the corresponding dose.
5 . The method of claim 1 , wherein the orally administering occurs approximately 2 hours after the human subject has eaten a meal.
6 . The method of claim 1 , wherein the inducing comprises inducing the human subject to sleep for 6 to 8 consecutive hours.
7 . The method of claim 1 , wherein the inducing comprises inducing the human subject to sleep for 8 consecutive hours.
8 . The method of claim 1 , wherein the orally administering comprises administering to the human subject a dose of the composition equivalent to 3.0 g to 12.0 g of sodium oxybate.
9 . The method of claim 1 , wherein the orally administering comprises administering to the human subject a dose of the composition equivalent to 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate.
10 . The method of claim 1 , wherein the pharmaceutical composition comprises the free base of gamma-hydroxybutyrate, a pharmaceutically acceptable salt of gamma-hydroxybutyric acid, any combination thereof, or any hydrate, solvate, complex or tautomer thereof.
11 . The method of claim 1 , wherein the pharmaceutical composition comprises one or more salts of gamma-hydroxybutyric acid selected from sodium salt of gamma-hydroxybutyric acid, potassium salt of gamma-hydroxybutyric acid, magnesium salt of gamma-hydroxybutyric acid, calcium salt of gamma-hydroxybutyric acid, lithium salt of gamma-hydroxybutyric, or tetra ammonium salt of gamma-hydroxybutyric acid.
12 . The method of claim 1 , wherein the pharmaceutical composition comprises sodium oxybate.
13 . The method of claim 1 , further comprising mixing the pharmaceutical composition with water after the opening and prior to the orally administering.
14 . The method of claim 13 , wherein the mixing results in the pharmaceutical composition being suspended in the water.
15 . The method of claim 13 , wherein the mixing comprises pouring pharmaceutical composition from the sachet into a container containing the water.
16 . The method of claim 1 , wherein the pharmaceutical composition comprises a modified release formulation of gamma-hydroxybutyrate.
17 . The method of claim 16 , wherein the modified release formulation comprises immediate release and modified release portions.
18 . The method of claim 16 , wherein the modified release formulation of gamma-hydroxybutyrate comprises particles with a volume mean diameter of from 100 to 1200 microns.
19 . The method of claim 16 , wherein the modified release formulation of gamma-hydroxybutyrate comprises particles with a volume mean diameter of from 200 to 800 microns.
20 . The method of claim 16 , wherein the modified release formulation of gamma-hydroxybutyrate comprises particles with a volume mean diameter of from 100 to 500 microns.
21 . The method of claim 16 , wherein the modified release formulation of gamma-hydroxybutyrate comprises particles with a volume mean diameter of about 320 microns.
22 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of from 10 to 1000 microns.
23 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of from 150 to 400 microns.
24 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of about 270 microns.
25 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of from 95 to 600 microns.
26 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of from 95 to 450 microns.
27 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of from 95 to 170 microns.
28 . The method of claim 17 , wherein the immediate release portion comprises particles with a volume mean diameter of about 140 microns.
29 . The method of claim 22 , wherein the immediate release portion comprises extruded particles.
30 . The method of claim 29 , wherein the extruded particles are spheronized.