Pharmaceutical compositions
Inventors
Brisander, Magnus • Demirbüker, Mustafa • Jesson, Gérald • Malmsten, Martin • Dérand, Helene
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11517562-B2
Publication Date
2022-12-06
Expiration Date
Abstract
The present invention relates to the field of methods for providing pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to compositions comprising stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions and in therapy.
Core Innovation
The invention relates to pharmaceutical compositions for the treatment of a leukemia, where the composition comprises particles including amorphous dasatinib. The particles further comprise at least one polymeric stabilizing and matrix-forming component selected from named cellulose derivatives, polyvinylpyrrolidone, polyvinyl acetate phthalate, copolyvidone, crospovidone, carbomer homopolymer types, methacrylic acid and ethylacrylate copolymer-related materials, and poloxamer, and the particles exclude at least one pharmaceutically acceptable solubilizer.
The particles are characterized as essentially amorphous hybrid nanoparticles and solid dispersion particles for poorly water-soluble protein kinase inhibitors. The disclosed compositions are intended to improve dissolution and solubility compared with raw crystalline protein kinase inhibitors, and the hybrid nanoparticles are described as having nanometer size, high amorphicity, and stability over storage.
The provided content also describes improved sink-condition dissolution rate and increases in area under the curve (AUC) for relevant protein kinase inhibitors, including improved performance in intestinal and gastric media conditions such as FaSSIF, FeSSIF, and SGF. It further states that physical mixing does not provide the same improvement as the amorphous hybrid nanoparticle formulation.
Claims Coverage
The partial content includes two independent claims. Both independent claims share the core formulation concept: amorphous dasatinib particles with polymeric stabilizing and matrix-forming components that exclude at least one pharmaceutically acceptable solubilizer, with one independent claim additionally requiring a tablet and excipient.
Amorphous dasatinib particles with polymeric stabilizing and matrix-forming component excluding solubilizer
A method for the treatment of a leukemia by administering a therapeutically effective amount of a composition comprising particles including amorphous dasatinib and at least one polymeric stabilizing and matrix-forming component selected from a defined group of polymers, wherein the particles exclude at least one pharmaceutically acceptable solubilizer.
Tablet comprising amorphous dasatinib particles with polymeric stabilizing and matrix-forming component excluding solubilizer and excipient
A method for the treatment of a leukemia by administering a therapeutically effective amount of a tablet comprising particles including amorphous dasatinib and at least one polymeric stabilizing and matrix-forming component selected from a defined group of polymers, wherein the particles exclude at least one pharmaceutically acceptable solubilizer, and further comprising an excipient.
Across both independent claims, the inventive coverage centers on administering a leukemia treatment using particles in a composition or tablet that contain amorphous dasatinib and at least one specified polymeric stabilizing and matrix-forming component while excluding at least one pharmaceutically acceptable solubilizer.
Stated Advantages
Improved dissolution and solubility versus raw crystalline protein kinase inhibitors.
Enhanced sink-condition dissolution rate.
Increased area under the curve (AUC) in the disclosed comparisons.
Physical mixing does not provide the same improvement as the amorphous hybrid nanoparticle formulation.
Documented Applications
Treatment of a leukemia by administering a therapeutically effective amount of a composition comprising amorphous dasatinib hybrid nanoparticles with polymeric stabilizing and matrix-forming components, with the particles excluding at least one pharmaceutically acceptable solubilizer.
Treatment of a leukemia using a tablet comprising the same type of particles and an excipient.
Dissolution and solubility evaluation using intestinal and gastric media conditions including FaSSIF, FeSSIF, and SGF, including sink-condition dissolution testing.
In vivo plasma exposure evaluation in beagle dogs after oral dosing (nilotinib), with storage and XRPD stability notes.
Interested in licensing this patent?