Aripiprazole prodrug compositions

Patent metadata

Field	Value
Publication number	US-10016415-B2
Application number	US-201514828229-A
Country	US
Kind code	B2
Filing date	Aug 17, 2015
Priority date	Aug 18, 2014
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

Described is a composition comprising (a) a population of particles of an aripiprazole prodrug having a volume based particle size (Dv50) of less than 1000 nm and (b) at least one surface stabilizer comprising an adsorbed component which is adsorbed on the surface of the aripiprazole prodrug particles and a free component available for solubilization of the aripiprazole prodrug. The surface stabilizer to prodrug ratio provides the optimal quantity of free surface stabilizer for the purposes of producing a lead-in formulation. Also described are methods of treatment using the aforementioned composition.

First claim

The invention claimed is:

1. A composition consisting of polysorbate 20 and a population of particles of the formula:

having a volume based particle distribution size (Dv50) between about 350 nm and about 175 nm as determined by light scattering techniques, wherein the ratio of said particles to polysorbate 20 is 17:1.

2. A composition consisting of polysorbate 20, a chelating agent, a tonicity agent, an aqueous buffer, and a population of particles of the formula:

having a volume based particle distribution size (Dv50) between about 350 nm and about 175 nm as determined by light scattering techniques, wherein the ratio of the particles to polysorbate 20 is 17:1.

3. The composition of claim 2 , wherein the chelating agent is sodium citrate.

4. The composition of claim 2 , wherein the tonicity agent is sodium chloride.

5. A composition consisting of polysorbate 20, sodium citrate, sodium chloride, an aqueous buffer, and a population of particles of the formula:

having a volume based particle distribution size (Dv50) between about 350 nm and about 175 nm as determined by light scattering techniques, wherein the ratio of the particles to polysorbate 20 is 17:1.

6. A composition consisting of:
(a) about 26 weight percent of a compound of the following formula:

(b) 1.53 weight percent polysorbate 20;
(c) 0.76 weight percent sodium citrate;
(d) 0.31 weight percent sodium chloride; and
(e) an aqueous buffer,
wherein the compound is provided as a population of particles having a volume based particle distribution size (Dv50) between about 350 nm and about 175 nm as determined by light scattering techniques.

7. The composition of claim 6 , wherein the ratio of the particles to polysorbate 20 is 17:1.

8. The composition of claim 2 , wherein the composition is an aqueous dispersion.

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Cresswell Philip
• Paquette Sara Montminy
• Hickey Magali
• Perkin Kristopher
• Smith Greg
• Liversidge Elaine
• Steinberg Brian
• Manser David
• Turncliff Ryan
• Palmieri Jr Michael
• Zeidan Tarek
• Cash Ethan P
• Hard Marjie L

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/496 Primary

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title