Pharmaceutical composition with improved bioavailability

Patent metadata

Field	Value
Publication number	US-10034854-B2
Application number	US-201615200419-A
Country	US
Kind code	B2
Filing date	Jul 1, 2016
Priority date	Jan 22, 2013
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The invention relates to solid dispersions of poorly water soluble compounds, in particular Compound A as disclosed herein, formed by solvent co-precipitation or spray drying, resulting in improved bioavailability, safety and tolerability of said compounds.

First claim

The invention claimed is:

1. A physically stable solid dispersion, comprising a compound having an aqueous solubility of less than 1 μg/ml and a melting point of >270° C. together with a stabilizing polymer, wherein the compound having an aqueous solubility of less than 1 μg/ml is 4-{[(2R, 3S, 4R, 5S)-4-(4-Chloro-2-Fluoro-Phenyl)-3-(3-Chloro-2-Fluoro-Phenyl)-4-Cyano-5-(2,2-Dimethyl-Propyl)-Pyrrolidine-2-Carbonyl]-Amino}-3-Methoxy-Benzoic Acid (Compound A):

and wherein the stabilizing polymer is EUDRAGIT® L-100 (Poly(methacrylic acid)-co-methyl methacrylate) or Eudragit® L100-55 (Poly(methacrylic acid)-co-methyl methacrylate).

2. The solid dispersion according to claim 1 wherein the ratio of the amount by weight of Compound A within the solid dispersion to the amount by weight of the stabilizing polymer therein is between 5:95 to 70:30.

3. The solid dispersion of claim 1 wherein the ratio of the amount by weight of the Compound A within the solid dispersion to the amount by weight of the stabilizing polymer therein is 30:70 to 50:50.

4. A unit dose solid formulation comprising: the solid dispersion according to claim 1 , together with commonly used pharmaceutical ingredients selected from the group consisting of disintegrants, diluents, lubricants and glidants together with a film coat.

5. A method for preparing a solid dispersion according to claim 1 , comprising the steps of forming a solution of Compound A and the polymer in dimethyl-acetamide, or any other suitable solvent and co-precipitating Compound A with the polymer using anti-solvent.

6. A pharmaceutical preparation containing the solid dispersion according to claim 1 , together with additional pharmaceutically acceptable adjuvants.

7. A method of treating prostate cancer, comprising the step of administering a therapeutically effective amount of the physically stable solid dispersion according to claim 1 to a patient in need thereof.

Assignees

• Hoffmann La Roche
• Hoffmann La Roche

Inventors

• Lomuscio Steve
• Ma Hua
• Matchett Michael Allen
• Sandhu Harpreet K
• Shah Navnit Hargovindas
• Zhang yu-e

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K9/2813

  Inorganic compounds · CPC title