Claims for Patent: 10,688,091

Summary for Patent: 10,688,091

Title:	Aripiprazole prodrug composition
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 solubilisation 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.
Inventor(s):	Cresswell; Philip (Athlone, IE), Hickey; Magali (Westwood, MA), Perkin; Kristopher (Athlone, IE), Smith; Greg (Norton, MA), Liversidge; Elaine (Charlestown, MA), Steinberg; Brian (Arlington, MA), Manser; David (Keenagh, IE), Zeidan; Tarek (Waltham, MA)
Assignee:	ALKERMES PHARMA IRELAND LIMITED (Dublin, IE)
Application Number:	16/416,818
Patent Claims:	1. A composition comprising: (a) a population of particles of an aripiprazole prodrug having a volume based particle distribution size (Dv50) of between 50 and 700 nm as determined by light scattering techniques; (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 solubilisation of the aripiprazole prodrug; wherein the ratio of aripiprazole prodrug to surface stabilizer is about 17:1; wherein the aripiprazole prodrug has the formula: ##STR00005## where n is zero or an integer less than 20; and wherein the at least one surface stabilizer is selected from the group consisting of carboxymethyl cellulose and polyoxyethylene sorbitan fatty acid esters. 2. The composition of claim 1, wherein in the aripiprazole prodrug formula n is equal to 4. 3. The composition of claim 1, wherein in the aripiprazole prodrug formula n is equal to 10. 4. The composition of claim 1, wherein the free component of the at least one surface stabilizer constitutes greater than 0% (w/w) and no more than about 3% (w/w) of the composition. 5. The composition of claim 1, wherein the volume based particle distribution size (Dv50) of the aripiprazole prodrug particles is between 175 nm and 350 nm. 6. The composition of claim 1, wherein the at least one surface stabilizer is a polyoxyethylene sorbitan fatty acid ester. 7. The composition of claim 1, wherein the at least one surface stabilizer is polysorbate 20. 8. The composition of claim 1, wherein the composition comprises a primary surface stabilizer and at least one secondary surface stabilizer. 9. The composition of claim 1, wherein the composition further comprises a dispersion medium in which the population of aripiprazole prodrug particles is dispersed, wherein the free component of the surface stabilizer is dissolved or otherwise dispersed within the dispersion medium. 10. The composition of claim 1, adapted for administration as a depot injection. 11. The composition of claim 1, wherein the composition is provided in an injection device, wherein the injection device is a pre-filled syringe, an auto-injector, a needleless syringe, or a dual chambered syringe. 12. The composition of claim 11, wherein the aripiprazole prodrug composition is provided in one chamber of the dual chambered syringe, and the other chamber of the dual chamber syringe is provided with a second composition. 13. The composition of claim 12, wherein the second composition is an aripiprazole prodrug composition, having a volume based particle distribution size (Dv50) of at least 200 nm, of at least 300 nm, of at least 400 nm, of at least 500 nm, of at least 600 nm, of at least 700 nm, of at least 800 nm, of at least 900 nm, of at least 1000 nm, of at least 1500 nm, of at least 2000 nm, of at least 5000 nm, of at least 10,000 nm greater than the aripiprazole prodrug composition, or the second composition is an atypical antipsychotic other than an aripiprazole prodrug. 14. The composition of claim 1, wherein the composition is formulated as a powder for reconstitution in a liquid medium, wherein the population of aripiprazole prodrug particles redisperse in the liquid medium such that the redispersed aripiprazole prodrug particles have a volume based particle distribution size (Dv50) of less than 1000 nm. 15. The composition of claim 1, further comprising an additional atypical antipsychotic other than the aripiprazole prodrug. 16. The composition of claim 1, wherein the viscosity of the composition is below 10 cP at a shear rate of about 100 s.sup.-1, when measured at a temperature of about 25.degree. C. 17. The composition of claim 1, wherein the composition comprises a population of particles of the formula: ##STR00006## having a volume based particle distribution size (Dv50) of between 350 nm and 175 nm as determined by light scattering techniques, wherein the ratio of said particles to polysorbate 20 is 17:1. 18. The composition of claim 17, wherein the composition further comprises a chelating agent, a tonicity agent, and a buffer. 19. The composition of claim 18, wherein the chelating agent is sodium citrate and the tonicity agent is sodium chloride. 20. The composition of claim 1, wherein the composition consists of: a) 26 weight percent of an aripiprazole prodrug of the following formula: ##STR00007## b) 1.53 weight percent polysorbate 20; c) 0.76 weight percent sodium citrate; d) 0.31 weight percent sodium chloride; e) 0.15 weight percent sodium phosphate buffer; and f) 71.25 weight percent water for injection; wherein the compound is provided as a population of particles having a volume based particle distribution size (Dv50) of 100 nm or 200 nm as determined by light scattering techniques. 21. The composition of claim 1, wherein the composition comprises a population of particles of the formula: ##STR00008## having a volume based particle distribution size (Dv50) of between 350 nm and 175 nm as determined by light scattering techniques, wherein the ratio of said particles to polysorbate 20 is about 17:1.