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a technology of pharmaceutical compositions and components, applied in the direction of drug compositions, microcapsules, cardiovascular disorders, etc., can solve the problems of uncontrolled cellular growth or change in cell-cell attachment properties, limited drug absorption from the gastrointestinal tract, and inconvenient storage of methods

Inactive Publication Date: 2014-12-25
XSPRAY MICROPARTICLES AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent describes methods for making stable and clear nanoparticles that contain a protein kinase inhibitor and a polymer that helps hold everything together. These nanoparticles can also have other substances added to them to make them even better.

Problems solved by technology

Mutations in cellular signaling proteins may cause such proteins to become expressed or activated at inappropriate levels or at inappropriate times during the cell cycle, which in turn may lead to uncontrolled cellular growth or changes in cell-cell attachment properties.
However, for certain drugs, drug absorption from the gastrointestinal tract is limited by poor aqueous solubility and / or poor membrane permeability of the drug molecules.
Traditionally, however, these methods carry inherent limitations concerning physical stabilities of the particles on storage, problems with grinding or difficulty of removal of the frequently toxic solvent.
Furthermore, it is important that the drug released from the solid phase does not precitipitate in the gastrointestinal tract, or precipitates as little as possible, but remains water-soluble in the aqueous fluids of the gastrointestinal tract, since such precipitation results in low bioavailability (see e.g. Nerve J. et al.
pH-dependent solubility is a well-known issue for many oral formulations of poorly water-soluble substances, such as PKIs, since most of the absorption of the drug occurs in the small and large intestine, where pH is close to neutral.

Method used

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example 1

Conclusions Example 1

[0166]Experiments 17-23 show that a solubility increase is obtained with stable, amorphous hybrid nanoparticles produced by the methods of the invention with nilotinib HCl and a polymeric stabilizing and matrix-forming component. Particular improvements are achieved with the polymeric stabilizing and matrix-forming components hydroxypropyl methylcellulose phthalate (HPMCP HP55) and polyvinyl acetate phthalate (PVAP). These improvements are not obtained when physically mixing nilotinib HCl with a polymeric stabilizing and matrix-forming component. Experiments 24-36 clearly shows that a further solubility increase is obtained with hybrid nanoparticles produced by the methods of the invention with nilotinib HCl and a polymeric stabilizing and matrix-forming component, wherein a separate solubilizer is added. Particular improvements are achieved by the addition of a separate solubilizer such as polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (S...

example 2

Conclusions Example 2

[0170]The experiments show that a solubility increase is obtained with stable, amorphous hybrid nanoparticles produced by the methods of the invention with erlotinib HCl and a polymeric stabilizing and matrix-forming component. Particular improvements are achieved with the polymeric stabilizing and matrix-forming component hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Experiments 65-66 and 72 show that a further solubility increase is obtained with hybrid nanoparticles produced by the methods of the invention with erlotinib HCl and a polymeric stabilizing and matrix-forming component, wherein a separate solubilizer is added. Particular improvements are achieved by the addition of a separate solubilizer added, wherein said solubilizer is selected from polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (Soluplus) and d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS). This improvement was not observed when the solubilizer...

example 3

Conclusions Example 3

[0174]The experiments show that a solubility increase is obtained with stable, amorphous hybrid nanoparticles produced by the methods of the invention with pazopanib and a polymeric stabilizing and matrix-forming component. Particular improvements are achieved with the polymeric stabilizing and matrix-forming component polyvinylpyrrolidone K-90 (PVP 90K). Experiments 91-92 show that a further solubility increase is obtained with hybrid nanoparticles produced by the methods of the invention with pazopanib and a polymeric stabilizing and matrix-forming component, wherein a separate solubilizer is added. Particular improvements are achieved by the addition of a separate solubilizer added, wherein said solubilizer is selected from polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (Soluplus) and d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS). This improvement was not observed when the solubilizer was incorporated into the hybrid nan...

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Abstract

The present invention relates to the field of methods for providing components of pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to methods for providing 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.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the field of methods for providing components of pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to methods for providing hybrid nanoparticles of protein kinase inhibitors (PKIs), in order to increase the dissolution rate and resulting bioavailability of said PKIs, useful in pharmaceutical compositions.BACKGROUND OF THE AND INVENTION[0002]Components of cellular signal transduction pathways that regulate the growth and differentiation of normal cells can, when dysregulated, lead to the development of cellular proliferative disorders and cancer. Mutations in cellular signaling proteins may cause such proteins to become expressed or activated at inappropriate levels or at inappropriate times during the cell cycle, which in turn may lead to uncontrolled cellular growth or changes in cell-cell attachment properties.[0003]Many proliferative disorders, such as tumors ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/51A61K31/517A61K31/437A61K31/44A61K31/4545A61K31/4439A61K31/506A61K31/5377B01F23/00
CPCA61K9/5161A61K31/506A61K31/517A61K31/5377A61K31/44A61K9/5146A61K31/4439A61K31/437A61K9/5192A61K9/5138A61K31/4545A61K31/444A61P27/02A61P35/00A61P35/02A61P43/00A61P9/00A61P9/10A61K47/32A61K47/38A61K9/0053A61K9/14A61K9/1641A61K9/1652
Inventor BRISANDER, MAGNUSDEMIRBUKER, MUSTAFAJESSON, GERALDMALMSTEN, MARTINDERAND, HELENE
Owner XSPRAY MICROPARTICLES AB