Lapatinib particles and uses thereof
Inventors
SITTENAUER, Jacob • FARTHING, Joseph • Williams, Mark • BALTEZOR, Michael • DiZerega, Gere • ABARCA, Aranza Barreda • Clark, Shelby
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12029818-B2
Publication Date
2024-07-09
Expiration Date
Abstract
The disclosure provides particles of at least 95% by weight of lapatinib, or a pharmaceutically acceptable salt thereof, wherein the particles have a specific surface area (SSA) of at least 10 m2/g and have a mean particle size by volume distribution of between about 0.7 μm and about 8 μm.
Core Innovation
The invention relates to lapatinib, or a pharmaceutically acceptable salt thereof, provided as particles that are highly enriched in lapatinib, with at least 95% by weight lapatinib in the particles. The particles are characterized by a specific surface area (SSA) of at least 11 m2/g, and a mean particle size by volume distribution between about 0.7 m and about 8 m. The particles are uncoated and exclude specified excipients.
The invention also encompasses suspension compositions including a pharmaceutically acceptable liquid carrier and optionally other formulation components, where the suspension includes the particles enriched in lapatinib (or salt) having the defined SSA and particle size distribution. The particles can be provided as lapatinib ditosylate monohydrate in some embodiments. Characterization is supported by particle size distribution (PSD), BET SSA, scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD) measurements.
In addition, the invention provides tumor-treatment methods that use the suspension composition for intra-tumoral and peri-tumoral injection, including intraperitoneal injection. The document describes improved dissolution at neutral pH using an ethanol-water medium (pH about 7 with 50% EtOH-water) for the high-SSA processed lapatinib particles compared with lower-SSA or unprocessed lapatinib.
Claims Coverage
Independent claim coverage centers on a lapatinib particle composition defined by three inventive features. Dependent claims add a bulk density constraint, higher or ranged SSA values, a specific salt/solvate form, and exclusion of specified excipients in uncoated particles.
Highly enriched lapatinib particle composition with SSA and size distribution
Particles comprising at least 95% by weight of lapatinib, or a pharmaceutically acceptable salt thereof; particles have a specific surface area (SSA) of at least 11 m2/g; and particles have a mean particle size by volume distribution of between about 0.7 m and about 8 m.
Bulk density constraint for the particle composition
The particles have a mean bulk density less than about 0.100 g/cm3, whether tapped or not tapped.
Higher SSA minimum
Particles have a specific surface area (SSA) of at least 18 m2/g.
SSA range constraint
Particles have a specific surface area (SSA) between 15 m2/g and about 50 m2/g.
Specific pharmaceutically acceptable salt/solvate form
Lapatinib as the pharmaceutically acceptable salt in the form of lapatinib ditosylate monohydrate.
Uncoated particles excluding specified excipients
Particles are uncoated and do not include specified polymers, proteins, and polyethylene glycol (PEG)-derived excipients, including polyethoxylated castor oil and polyethylene glycol glycerides composed of mono-, di- and triglycerides, and mono- and diesters of polyethylene glycol.
The coverage centers on highly enriched lapatinib particles defined by minimum and/or range SSA values together with a mean particle size by volume distribution, with additional refinements including a bulk density limit, specification of lapatinib ditosylate monohydrate, and exclusion of specified excipients via an uncoated particle requirement.
Stated Advantages
Improved dissolution at neutral pH for high-SSA processed lapatinib particles compared with lower-SSA or unprocessed lapatinib.
Documented Applications
Tumor treatment using a suspension composition for intra-tumoral and peri-tumoral injection, including intraperitoneal injection.
Interested in licensing this patent?