US 11,896,572 B2
Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Jordan Dubow, Lyons (FR); Hervé Guillard, Villeurbanne (FR); Claire Mégret, Lyons (FR); and Jean-François Dubuisson, Lyons (FR)
Assigned to Flamel Ireland Limited, Dublin (IE)
Filed by Flamel Ireland Limited, Dublin (IE)
Filed on Aug. 8, 2023, as Appl. No. 18/231,581.
Application 18/231,581 is a continuation of application No. 18/075,980, filed on Dec. 6, 2022, granted, now 11,766,418.
Application 18/075,980 is a continuation of application No. 17/497,393, filed on Oct. 8, 2021, granted, now 11,602,513, issued on Mar. 14, 2023.
Application 17/497,393 is a continuation in part of application No. 17/178,117, filed on Feb. 17, 2021.
Application 17/178,117 is a continuation in part of application No. 16/527,633, filed on Jul. 31, 2019, granted, now 11,065,224, issued on Jul. 20, 2021.
Application 16/527,633 is a continuation of application No. 16/281,235, filed on Feb. 21, 2019, granted, now 10,736,866, issued on Aug. 11, 2020.
Application 16/281,235 is a continuation of application No. 15/655,924, filed on Jul. 21, 2017, granted, now 10,272,062, issued on Apr. 30, 2019.
Claims priority of provisional application 62/474,330, filed on Mar. 21, 2017.
Claims priority of provisional application 62/399,413, filed on Sep. 25, 2016.
Claims priority of provisional application 62/365,812, filed on Jul. 22, 2016.
Prior Publication US 2023/0381131 A1, Nov. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/22 (2006.01); A61K 9/16 (2006.01); A61K 9/50 (2006.01); A61K 31/19 (2006.01); A61K 9/14 (2006.01)
CPC A61K 31/22 (2013.01) [A61K 9/14 (2013.01); A61K 9/1676 (2013.01); A61K 9/5015 (2013.01); A61K 9/5026 (2013.01); A61K 9/5042 (2013.01); A61K 9/5078 (2013.01); A61K 9/5084 (2013.01); A61K 31/19 (2013.01)] 1 Claim
 
1. A pharmaceutical composition comprising:
immediate release particles, each of which comprises:
a core consisting of microcrystalline cellulose; and
a sodium oxybate loaded layer covering the core and containing a binder comprising povidone, wherein the immediate release particles have a volume mean diameter of 150 to 400 microns;
delayed release particles having a pH trigger, each delayed release particle comprising:
a core consisting of microcrystalline cellulose;
a sodium oxybate loaded layer covering the core of each delayed release particle and containing a binder comprising povidone; and
a coating covering the sodium oxybate loaded layer of each delayed release particle, wherein the coating consists essentially of hydrogenated vegetable oil, methacrylic acid copolymer type C and methacrylic acid copolymer type B, wherein a weight ratio of the hydrogenated vegetable oil to the copolymers types B and C is from 0.4 to 4, and wherein the coating is from 10 to 50% of the weight of the delayed release particles, and wherein the delayed release particles have a volume mean diameter of 200 to 800 microns;
a suspending or viscosifying agent comprising 2% to 5% by weight of the composition, the suspending or viscosifying agent being a mixture of xanthan gum, carrageenan and hydroxyethylcellulose; and
an acidifying agent comprising 1.2% to 5% by weight of the composition, the acidifying agent being malic acid,
wherein the composition comprises from 3.0 to 12.0 g of sodium oxybate,
wherein a ratio of sodium oxybate in the immediate release particles and the delayed release particles is from 40/60 to 60/40,
wherein the composition is in the form of a powder that is intended to be suspended in water prior to oral administration, and
wherein the suspending or viscosifying agent and the acidifying agent are separate from the immediate release particles and the delayed release particles.