# US 10,478,434 B2 · Crystallization process of aripiprazole derivatives in extended release formulations for treatment of schizophrenia > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,434 B2 - Document ID: US10478434B2 - Status: Granted - Kind: B2 - Application number: 16/043,721 - Filed: 2018-07-24 - Published: 2019-01-17 - Granted: 2019-11-19 - Earliest claimed: 2014-08-25 - Assignees: Alkermes Pharma Ireland Limited - Applicants: Alkermes Pharma Ireland Limited - Inventors: Wilfredo Morales; Tarek A. Zeidan; Renato A. Chiarella; Steven G. Wright; Jason M. Perry - Web page: https://patentgrep.com/patent/US10478434B2 ## CPC - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/00: Medicinal preparations containing organic active ingredients - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - C07D 215/22: attached in position 2 or 4 - C07D 401/12: linked by a chain containing hetero atoms as chain links - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Processes for providing depot injections of recrystallized aripiprazole lauroxil in which particles of the aripiprazole lauroxil have a surface area of about 0.50 to about 3.3 m2/g; and crystals of aripiprazole lauroxil produced by such processes. ## Claims ### Claim 1 A process for making a compound of Formula (A) in crystal form: wherein Ra is CH2OC(O)R1 and wherein R1 is a substituted or unsubstituted aliphatic moiety; the process comprising the steps of: (a) dissolving the compound of Formula (A) or a salt or solvate thereof in a first solvent to form a homogeneous drug solution; (b) optionally combining the drug solution with a second solvent; (c) cooling the solution; and (d) when the temperature of the solution is within the range of about 31-38° C., further homogenizing the solution to induce formation of the compound of Formula (A) in crystal form. ### Claim 2 (depends on 1) The process of claim 1, further comprising the steps of: (e) stopping the homogenization, and re-dissolving the compound of Formula (A) in crystal form by heating the solution; (f) cooling the solution; and (g) when the temperature of the solution is within the range of about 31-38° C., further homogenizing the solution to induce formation of the compound of Formula (A) in crystal form. ### Claim 3 (depends on 1) The process of claim 1, wherein the crystallized particles have a surface area of about 0.50 to about 3.3 m2/g. ### Claim 4 (depends on 1) The process of claim 1, wherein the crystallized particles have a surface area of about 0.80 to about 1.1 m2/g. ### Claim 5 (depends on 1) The process of claim 1, wherein the crystallized particles have a surface area of about 1.00 m2/g. ### Claim 6 (depends on 1) The process of claim 1, wherein the Dv[50] of the crystallized particles is about 10 to about 30 microns. ### Claim 7 (depends on 1) The process of claim 1, wherein the Dv[50] of the crystallized particles is about 10 to about 20 microns. ### Claim 8 (depends on 1) The process of claim 1, wherein in step (a), the first solvent is isopropyl acetate. ### Claim 9 (depends on 1) The process of claim 1, wherein in step (a), the first solvent is a mixture of isopropyl acetate and n-heptane. ### Claim 10 (depends on 1) The process of claim 1, wherein in step (b), the second solvent is n-heptane. ### Claim 11 (depends on 1) The process of claim 1, wherein in step (b), the temperature of the solution is in the range of about 55° C. to about 65° C. ### Claim 12 (depends on 1) The process of claim 1, wherein in step (d), the temperature of the solution is within the range of about 31-35° C. ### Claim 13 (depends on 1) The process of claim 1, wherein in step (d), the temperature of the solution is about 34° C. ### Claim 14 (depends on 1) The process of claim 1, wherein one or more of steps (a) through (c) is performed under agitation. ### Claim 15 (depends on 2) The process of claim 2, wherein one or more of steps (a), (b), (c), (d), (e), (f), and (g) is performed under agitation. ### Claim 16 (depends on 1) The process of claim 1, wherein the process further comprises the step of filtering the crystallized particles. ### Claim 17 (depends on 16) The process of claim 16, wherein the process further comprises the step of rinsing the crystallized particles. ### Claim 18 (depends on 17) The process of claim 17, wherein the process further comprises the step of drying the crystallized particles. ### Claim 19 (depends on 1) The process of claim 1, wherein the compound of Formula (A) is selected from the group consisting of: ### Claim 20 (depends on 2) The process of claim 2, wherein the compound of Formula (A) is selected from the group consisting of: ### Claim 21 (depends on 1) The process of claim 1, wherein the solution of step (d) is further homogenized by a homogenizer. ### Claim 22 (depends on 19) The process of claim 19, wherein the compound of Formula (A) is a compound of Formula (I): ### Claim 23 (depends on 20) The process of claim 20, wherein the compound of Formula (A) is a compound of Formula (I):