Niraparib particles and uses thereof

Patent metadata

Field	Value
Publication number	US-11738014-B2
Application number	US-202218053491-A
Country	US
Kind code	B2
Filing date	Nov 8, 2022
Priority date	Nov 10, 2021
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

Compositions of particles having at least 95% by weight of niraparib and a specific surface area (SSA) of at least 5 m 2 /g, methods for their use, and methods for their production are provided.

First claim

We claim:

1. A composition, comprising particles comprising at least 95% by weight of niraparib, or a pharmaceutically acceptable salt thereof, wherein the particles have a specific surface area (SSA) of at least 5 m 2 /g.

2. The composition of claim 1 , wherein the particles have a SSA of at least 10 m 2 /g.

3. The composition of claim 1 , wherein the particles have a SSA of at least 15 m 2 /g.

4. The composition of claim 1 , wherein the particles have a SSA of between 5 m 2 /g and about 50 m 2 /g.

5. The composition of claim 1 , wherein the particles have a mean particle size by volume distribution (Dv50) of from about 1.0 micron to about 10.0 microns in diameter.

6. The composition of claim 1 , wherein the particles have a mean bulk density (not tapped) between about 0.020 g/cm 3 and about 0.500 g/cm 3 .

7. The composition of claim 1 , wherein the particles have a mean tapped density of between about 0.050 g/cm 3 and about 0.600 g/cm 3 .

8. The composition of claim 1 , wherein the particles comprise at least 98%, by weight of niraparib, or a pharmaceutically acceptable salt thereof.

9. The composition of claim 1 , wherein the particles are uncoated and exclude polymer, protein, polyethoxylated castor oil and polyethylene glycol glycerides composed of mono-, di- and triglycerides and mono- and diesters of polyethylene glycol.

10. The composition of claim 1 , wherein the composition comprises a suspension further comprising a pharmaceutically acceptable liquid carrier.

11. The composition of claim 1 , further comprising one or more components selected from the group consisting of polysorbate, methylcellulose, polyvinylpyrrolidone, mannitol, and hydroxypropyl methylcellulose.

12. The composition of claim 1 , wherein the suspension is aerosolized, and the mass median aerodynamic diameter (MMAD) of aerosol droplets of the suspension between about 0.5 μm to about 6 μm diameter.

13. The composition of claim 1 , wherein
(a) the composition is a dry powder composition, wherein the dry powder composition does not comprise a carrier or any excipients, and wherein the dry powder composition is aerosolized, and the MMAD of the aerosolized dry powder composition between about 0.5 μm to about 6 μm in diameter, or
(b) the composition is a dry powder composition, wherein the dry powder composition comprises a pharmaceutically acceptable dry powder carrier comprising one or more dry powder excipients, and wherein the dry powder composition is aerosolized, and the MMAD of the aerosolized dry powder composition is between about 0.5 μm to about 6 μm in diameter.

14. The composition of claim 1 , wherein the pharmaceutically acceptable salt of niraparib comprises niraparib tosylate monohydrate.

15. A method for treating a tumor, comprising administering to a subject with a tumor an amount effective to treat the tumor of the composition of claim 1 .

16. A method for making niraparib particles, comprising:
(a) introducing (i) a solution comprising at least one solvent selected from the group consisting of ethanol, methanol, hexafluoroisopropanol (HFIP), or combinations thereof, and at least one solute comprising niraparib or a pharmaceutically acceptable salt thereof into a nozzle inlet, and (ii) a compressed fluid into an inlet of a vessel defining a pressurizable chamber;
(b) passing the solution out of a nozzle orifice and into the pressurizable chamber to produce an output stream of atomized droplets, wherein the nozzle orifice is located between 2 mm and 20 mm from a sonic energy source located within the output stream, wherein the sonic energy source produces sonic energy with an amplitude between 10% and 100% during the passing, and wherein the nozzle orifice has a diameter of between 20 μm and 125 μm;
(c) contacting the atomized droplets with the compressed fluid, to cause depletion of the solvent from the atomized droplets, to produce niraparib particles comprising at least 95% niraparib or a pharmaceutically acceptable salt thereof, wherein the niraparib particles have a specific surface area (SSA) of at least 5 m 2 /g,
wherein steps (a), (b), and (c) are carried out under supercritical temperature and pressure for the compressed fluid.

17. The method of claim 16 , further comprising:
(d) contacting the compound particles produced in step (c) with an anti-solvent to cause further depletion of the solvent from the compound particles, wherein step (d) is carried out under supercritical temperature and pressure for the anti-solvent.

Assignees

• Crititech Inc

Inventors

• Sittenauer Jacob
• Abarca Aranza Barreda
• Clark Shelby
• Farthing Joseph
• Williams Mark
• Dizerega Gere
• Baltezor Michael

Classifications

• A61K45/06

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

• A61K31/454 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K9/0078

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · CPC title

• 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

• A61K9/10

  Dispersions; Emulsions · CPC title