Rucaparib particles and uses thereof
Inventors
SITTENAUER, Jacob • ABARCA, Aranza Barreda • Clark, Shelby • FARTHING, Joseph • Williams, Mark • DiZerega, Gere • BALTEZOR, Michael
Assignees
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Publication Number
US-11738029-B2
Publication Date
2023-08-29
Expiration Date
Abstract
Compositions of particles having at least 95% by weight of rucaparib and a specific surface area (SSA) of at least 12 m2/g, methods for their use, and methods for their production are provided.
Core Innovation
The disclosure provides rucaparib particle compositions in which the particles comprise at least 95% by weight of rucaparib, or a pharmaceutically acceptable salt thereof, and the particles exhibit a specific surface area (SSA) of at least 12 m2/g. The compositions include high-surface area rucaparib particles, including embodiments where the rucaparib is present as a pharmaceutically acceptable salt such as rucaparib camsylate. Particle-property ranges are described, including optional particle size characteristics, bulk/tapped density ranges, and amorphous or crystalline forms.
The document further describes therapeutic use formulations incorporating these rucaparib particles for treating tumors, including liquid suspensions and aerosolized inhalation formulations. For aerosolized formulations, the document specifies an MMAD range for an aerosolized dry powder composition, and it also addresses optional dry powder carriers and/or dry powder excipients. In addition, the disclosure discusses particle and composition characteristics such as uncoated particles and exclusions or inclusions of particular excipient classes.
A further aspect of the disclosure is a method for making rucaparib particles by producing atomized droplets from a solution comprising at least one solvent selected from ethanol, methanol, HFIP, DMF, DMSO, or combinations thereof, and a solute comprising rucaparib or a pharmaceutically acceptable salt, into a process vessel. The method includes passing the solution out of a nozzle orifice located a defined distance from a sonic energy source within the output stream, applying sonic energy with a defined amplitude, and contacting the atomized droplets with compressed fluid to cause depletion of the solvent under supercritical temperature and pressure to produce rucaparib particles comprising at least 95% rucaparib, or salt, and having SSA of at least 12 m2/g.
Claims Coverage
The provided independent claims cover a high-specific surface area rucaparib particle composition meeting defined rucaparib content and SSA thresholds, and a supercritical compressed-fluid atomization and solvent-depletion method that yields rucaparib-rich particles meeting the same rucaparib content and SSA thresholds. Across the claim set, multiple inventive features are refined by dependent claim limitations regarding particle size, density, particle form, salt identity, formulation type, MMAD range, and selected excipient exclusions.
Rucaparib-rich high-specific surface area particle composition
A composition comprising particles comprising at least 95% by weight of rucaparib, or a pharmaceutically acceptable salt thereof, wherein the particles have a specific surface area (SSA) of at least 12 m2/g.
Tightened SSA threshold
Particles having a specific surface area (SSA) of at least 13 m2/g.
Volume-based particle size constraint (Dv50)
Particles having a volume-based mean particle size (Dv50) ranging from about 1.0 to about 10.0 microns in diameter.
Bulk density (not tapped) range
Particles having a mean bulk density (not tapped) between about 0.020 g/cm3 and about 0.300 g/cm3.
Aerosolized dry powder with specified MMAD
A pharmaceutical composition as an aerosolized dry powder having an MMAD of about 0.5–6 μm, either without any carrier or excipients or with a pharmaceutically acceptable dry powder carrier that includes one or more dry powder excipients.
Uncoated particles and excipient exclusions
The particles are uncoated and the composition excludes certain polymeric and surfactant excipients.
Supercritical compressed-fluid atomization and solvent depletion
A method for making rucaparib particles comprising introducing a solution comprising at least one solvent including ethanol, methanol, HFIP, DMF, DMSO, or combinations thereof, and at least one solute comprising rucaparib or a pharmaceutically acceptable salt into a nozzle inlet, passing the solution out of a nozzle orifice located between 2 mm and 20 mm from a sonic energy source located within the output stream while sonic energy is produced with an amplitude between 10% and 100%, contacting the atomized droplets with compressed fluid to deplete the solvent from the atomized droplets, and carrying out the steps under supercritical temperature and pressure for the compressed fluid to produce rucaparib particles comprising at least 95% rucaparib, or salt, and having SSA of at least 12 m2/g.
Defined sonic-energy placement and nozzle-orifice geometry/size
Nozzle orifice located between 2 mm and 20 mm from a sonic energy source within the output stream, sonic energy amplitude between 10% and 100% during passing, and nozzle orifice diameter between 20 μm and 125 μm.
Taken together, the claims set define rucaparib, or a pharmaceutically acceptable salt, particle compositions requiring at least 95% by weight drug content and SSA at least 12 m2/g, further narrowed by particle size, density, form, and formulation characteristics, and a supercritical process using nozzle atomization with sonic energy and compressed-fluid solvent depletion to produce rucaparib-rich, high-SSA particles.
Stated Advantages
Improved dissolution for processed particles versus raw material is reported in the experimental/disclosure content.
The disclosed process is described as providing particle compositions that discriminate in solubility and dissolution testing versus raw material, consistent with improved dissolution behavior.
Documented Applications
Treating tumors by administering rucaparib particle compositions, including liquid suspensions and aerosolized inhalation formulations.
Using aerosolized dry powder formulations for inhalation, with specified MMAD for the aerosolized dry powder composition.
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