FORMULATIONS OF PIMAVANSERIN

• US 20200009122A1
• Filed: 09/16/2019
• Published: 01/09/2020
• Est. Priority Date: 08/30/2017
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Tejwani, Ravi, Abele, Stephen Edward, Vizzotti, Emanuel Joseph
• Granted Patent: US 10,646,480 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs

Abstract

Provided herein are capsules containing pimavanserin, processes for manufacturing said capsule, and pharmaceutical compositions containing pimavanserin.

Claims

1. A pharmaceutically acceptable capsule for orally delivering 34 mg of pimavanserin to a patient, wherein the capsule has a size 3 or 4 capsule shell that encapsulates a blended pimavanserin composition comprising:

40 mg granulated pimavanserin tartrate having wherein the bulk density of the granulated pimavanserin tartrate is 0.4 to 0.6 g/ml as determined by USP<

616>

, method 1;

microcrystalline cellulose having a particle size distribution (D90) of 180 to 340 μ

m;

wherein the particle size distribution is measured using laser light scattering with a Malvern Mastersizer 2000 LLS PS system, a Scirocco 2000 dry dispersion unit and a sample size of 2 to 10 g.

2. The pharmaceutically acceptable capsule of claim 1, wherein the capsule shell is a hard shell size 4 capsule.

3. The pharmaceutically acceptable capsule of claim 1, wherein the blended pimavanserin composition further comprises a lubricant.

4. The pharmaceutically acceptable capsule of claim 3, wherein the lubricant is magnesium stearate.

10. The pharmaceutically acceptable capsule of claim 1, wherein the capsule is stable upon actual or simulated storage under open conditions at 25°

C.±

2°

/60%±

5% relative humidity for 1 year.

5. A pharmaceutically acceptable capsule for orally delivering 34 mg of pimavanserin to patient, wherein the capsule has a size 3 or 4 capsule shell that contains a blended pimavanserin composition comprising:

40 mg granulated pimavanserin tartrate wherein the bulk density of the granulated pimavanserin tartrate is 0.4 to 0.6 g/ml as determined by USP<

616>

, method 1; and

57-60% w/w microcrystalline cellulose.

6. The pharmaceutically acceptable capsule of claim 5, wherein the blended pimavanserin composition further comprises 0.1 to 3% w/w magnesium stearate.

7. The pharmaceutically acceptable capsule of claim 5, wherein the bulk density of the blended pimavanserin composition is 0.4 to 0.6 g/ml as determined by USP <

616>

, method 1.

8. The pharmaceutically acceptable capsule of claim 5, wherein the microcrystalline cellulose has a particle size distribution (D90) of 180 to 340 μ

m and wherein the particle size distribution is measured using laser light scattering with a Malvern Mastersizer 2000 LLS PS system, a Scirocco 2000 dry dispersion unit and a sample size of 2 to 10 g.

9. The pharmaceutically acceptable capsule of claim 5, wherein the capsule releases at least 80% of the pimavanserin within 30 minutes in accordance with USP <

711>

dissolution apparatus 1.

11. The pharmaceutically acceptable capsule of claim 5, wherein the capsule is stable upon actual or simulated storage under open conditions at 25°

C.±

2°

/60%±

5% relative humidity for 1 year.

12. A pharmaceutically acceptable capsule for orally delivering 34 mg of pimavanserin to patient, wherein the capsule has a size 3 or 4 capsule shell that contains a blended pimavanserin composition comprising:

40 mg granulated pimavanserin tartrate wherein the bulk density of the granulated pimavanserin tartrate is 0.4 to 0.6 g/ml as determined by USP<

616>

, method 1;

a filler and a lubricant, wherein

the D90 particle size distribution of the blended pimavanserin composition is 100 to 300 μ

m as measured using laser scattering particle size analysis.

13. The pharmaceutically acceptable capsule of claim 12, wherein the capsule has a size 4 capsule shell.