LURASIDONE SOLID DISPERSION AND PREPARATION METHOD THEREOF

• US 20190321304A1
• Filed: 01/04/2018
• Published: 10/24/2019
• Est. Priority Date: 01/06/2017
• Status: Active Grant

• Current Assignee: Sunshine Lake Pharma Co Ltd (Shenzhen Dongyangguang Industry Co., Ltd.)
• Original Assignee: Sunshine Lake Pharma Co Ltd (Shenzhen Dongyangguang Industry Co., Ltd.)
• Inventors: XU, Yuzhen, TIAN, Ning, HUANG, Xin, YOU, Jinsong, HUANG, Fangfang
• Granted Patent: US 11,090,272 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

It relates to a lurasidone solid dispersion and a preparation method, wherein the method comprises melting treatment of a mixture containing lurasidone, a medicinal hot melt carrier, optionally an acidic regulator and plasticizer in order to obtain the solid dispersion described herein, and wherein the lurasidone is provided in a form of free base. The lurasidone solid dispersion obtained by the preparation method according to the example of the invention has the characteristics of high dissolution rate (dissolution rate can reach 30%-70%) in a partial neutral medium (e.g. pH6.0). The bioavailability of lurasidone solid dispersion increased significantly and the food effect of lurasidone solid dispersion prepared from the example decreased remarkably. It overcomes the limitation of too many medication in the prior art and avoids the reduction of curative effect of the improper medication for the patient or even invalid, ensures the normal efficacy, thereby increases the patient'"'"'s medication flexibility and compliance.

Claims

1. A lurasidone solid dispersion comprising lurasidone, a medicinal hot melt carrier and an acidic regulator, wherein the lurasidone is in a form of free base.

2. The lurasidone solid dispersion according to claim 1, wherein a weight ratio of the lurasidone to the medicinal hot melt carrier is ranged from about 1:

1 to about 1;

50,

optionally, wherein the medicinal hot melt carrier comprises at least one of povidone, copovidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, a hydroxypropyl methyl cellulose acetate succinate, a polyethylene glycol, a hydroxypropyl methyl cellulose, hydroxypropyl cellulose, an ethyl cellulose and an acrylic resin,

optionally, wherein a weight ratio of the lurasidone to the acidic regulator is ranged from about 1;

0.05 to about 1;

25, and

optionally, wherein the acidic regulator comprises at least one of citric acid monohydrate, anhydrous citric acid, fumaric acid, malic acid, succinic acid, ascorbic acid, tartaric acid, sorbic acid and glycine.

3. The lurasidone solid dispersion according to claim 1, wherein the lurasidone solid dispersion further comprises a plasticizer,

optionally, wherein a weight ratio of the lurasidone to the plasticizer is ranged from about 1:

0 to about 1;

10, and

optionally, wherein the plasticizer comprises at least one of a poloxamer, a polyethylene glycol, triethyl citrate, diethyl phthalate, and glycerol monostearate.

13. A pharmaceutical composition comprising the lurasidone solid dispersion according to claim 1,

optionally, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient;

optionally, wherein the pharmaceutically acceptable excipient comprises at least one of a filler, a disintegrant, an adhesive, a surfactant, a flavoring agent and a lubricant;

optionally, wherein the filler comprises at least one of lactose, starch, microcrystalline cellulose, mannitol, dextrin, pregelatinized starch, corn starch, sorbitol, calcium sulfate, calcium hydrogen phosphate and calcium carbonate;

optionally, wherein the disintegrant comprises at least one of crospovidone, croscarmellose sodium, sodium starch glycolate, dry starch and low-substituted hydroxypropyl cellulose;

optionally, wherein the adhesive comprises at least one of starch, pregelatinized starch, sodium carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, an ethylcellulose, a hypromellose, sucrose, gelatin, polyvinylpyrrolidone, microcrystalline cellulose and copovidone;

optionally, wherein the surfactant comprises at least one of sodium lauryl sulfate, quaternary ammonium compound, lecithin, fatty acid glycerides, sorbitan fatty acid ester and polysorbate;

optionally, wherein the flavoring agent comprises at least one of sucrose, sucralose, acesulfame, aspartame, stevioside, sodium saccharin and sodium cyclamate;

optionally, wherein the lubricant comprises at least one of magnesium stearate, colloidal silicon dioxide, stearic acid, talc, glyceryl behenate, hydrogenated castor oil, sodium stearyl fumarate;

optionally, wherein the pharmaceutical composition is in a form of granule, tablet, capsule or enteric-coated preparation.

14. A pharmaceutical combination characterized in that the pharmaceutical combination is for use in treating or preventing a mental disease, comprising:

lurasidone used as a first active agent, wherein the lurasidone exists in a form of lurasidone solid dispersion according to claim 1; and

a medicament different from lurasidone used as a second active agent, wherein the medicament is used for treating or preventing a mental disease.

23. A method of treating or preventing a mental disease in a patient, comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition according to claim 13.

4. A method of preparing lurasidone solid dispersion comprising:

melting and mixing a mixture containing lurasidone and a medicinal hot melt carrier; and

cooling the mixture to give the lurasidone solid dispersion, wherein the lurasidone is in a form of free base.

6. The method according to claim 4, wherein the melting and mixing step is carried out in a hot melt extruder.

7. The method according to claim 4, wherein a weight ratio of the lurasidone to the medicinal hot melt carrier is ranged from about 1:

1 to about 1;

50,

optionally, wherein the medicinal hot melt carrier comprises at least one of povidone, copovidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, a hydroxypropyl methyl cellulose acetate succinate, a polyethylene glycol, a hydroxypropyl methyl cellulose, hydroxypropyl cellulose, an ethyl cellulose and an acrylic resin.

9. The method according to claim 4, wherein the mixture further comprises a plasticizer,

optionally, wherein a weight ratio of the lurasidone to the plasticizer is ranged from about 1:

0 to about 1;

10,

optionally, wherein the plasticizer comprises at least one of a poloxamer, a polyethylene glycol, triethyl citrate, diethyl phthalate and glycerol monostearate.

10. The method according to claim 6, wherein the melting and mixing step is carried out at a temperature from about 80°

C. to about 200°

C. while the screw speed of the hot melt extruder is from about 30 rpm to about 1000 rpm.

11. The method according to claim 6, wherein the melting and mixing step is carried out at a temperature from about 115°

C. to about 175°

C. while the screw speed of the hot melt extruder is from about 30 rpm to about 300 rpm.

12. A lurasidone solid dispersion prepared by the method according to claim 4.

17. A method of treating or preventing a mental disease in a patient, comprising administering to the patient a therapeutically effective amount of the lurasidone solid dispersion according to claim 12.

21. A pharmaceutical composition comprising the lurasidone solid dispersion according to claim 12,

optionally, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable excipient;

optionally, wherein the pharmaceutically acceptable excipient comprises at least one of a filler, a disintegrant, an adhesive, a surfactant, a flavoring agent and a lubricant;

optionally, wherein the filler comprises at least one of lactose, starch, microcrystalline cellulose, mannitol, dextrin, pregelatinized starch, corn starch, sorbitol, calcium sulfate, calcium hydrogen phosphate and calcium carbonate;

optionally, wherein the disintegrant comprises at least one of crospovidone, croscarmellose sodium, sodium starch glycolate, dry starch and low-substituted hydroxypropyl cellulose;

optionally, wherein the adhesive comprises at least one of starch, pregelatinized starch, sodium carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, an ethylcellulose, a hypromellose, sucrose, gelatin, polyvinylpyrrolidone, microcrystalline cellulose and copovidone;

optionally, wherein the surfactant comprises at least one of sodium lauryl sulfate, quaternary ammonium compound, lecithin, fatty acid glycerides, sorbitan fatty acid ester and polysorbate;

optionally, wherein the flavoring agent comprises at least one of sucrose, sucralose, acesulfame, aspartame, stevioside, sodium saccharin and sodium cyclamate;

optionally, wherein the lubricant comprises at least one of magnesium stearate, colloidal silicon dioxide, stearic acid, talc, glyceryl behenate, hydrogenated castor oil, sodium stearyl fumarate;

optionally, wherein the pharmaceutical composition is in a form of granule, tablet, capsule or enteric-coated preparation.

22. A pharmaceutical combination characterized in that the pharmaceutical combination is for use in treating or preventing a mental disease, comprising:

lurasidone used as a first active agent, wherein the lurasidone exists in a form of lurasidone solid dispersion according to claim 12; and

a medicament different from lurasidone used as a second active agent, wherein the medicament is used for treating or preventing a mental disease.

5. A method of preparing lurasidone solid dispersion comprising:

melting and mixing a mixture containing lurasidone, a medicinal hot melt carrier, an acidic regulator, and optionally a plasticizer; and

cooling the mixture to give the lurasidone solid dispersion, wherein the lurasidone is in a form of free base.

8. The method according to claim 5, wherein a weight ratio of the lurasidone to the acidic regulator is ranged from about 1:

0.05 to about 1;

25,

optionally, wherein the acidic regulator comprises at least one of citric acid, fumaric acid, malic acid, succinic acid, ascorbic acid, tartaric acid, sorbic acid and glycine.

18. The method according to claim 5, wherein the melting and mixing step is carried out in a hot melt extruder.

19. The method according to claim 5, wherein a weight ratio of the lurasidone to the medicinal hot melt carrier is ranged from about 1:

1 to about 1;

50,

optionally, wherein the medicinal hot melt carrier comprises at least one of povidone, copovidone, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, a hydroxypropyl methyl cellulose acetate succinate, a polyethylene glycol, a hydroxypropyl methyl cellulose, hydroxypropyl cellulose, an ethyl cellulose and an acrylic resin.

20. A lurasidone solid dispersion prepared by the method according to claim 5.

15-16. -16. (canceled)