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 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.