Anticancer compositions

Abstract

The present invention concerns pharmaceutical formulations of ARN-509, which can be administered to a mammal, in particular a human, suffering from an androgen receptor (AR)-related disease or condition, in particular cancer, more in particular prostate cancer, including but not limited to castration-resistant prostate cancer, metastatic castration resistant prostate cancer, chemotherapy-naïve metastatic castration resistant prostate cancer, biochemically relapsed hormone sensitive prostate cancer, or high-risk, non-metastatic castration-resistant prostate cancer. In one aspect, these formulations comprise a solid dispersion of ARN-509 and HPMCAS. In one aspect, the solid dispersion of ARN-509 and HPMCAS is obtainable, in particular is obtained, by melt-extruding a mixture comprising ARN-509 and HPMCAS and optionally subsequently milling said melt-extruded mixture. In one aspect, the solid dispersion of ARN-509 and HPMCAS is obtainable, in particular is obtained, by spray drying a mixture comprising ARN-509 and HPMCAS in a suitable solvent.

1 . A solid dispersion comprising 
       
         
           
           
               
               
           
         
       
       methylcellulose acetate succinate (HPMCAS). 
     
     
         2 . The solid dispersion according to  claim 1  wherein the dispersion consists of ARN-509 and HPMCAS. 
     
     
         3 . The solid dispersion according to  claim 1  wherein ARN-509 and HPMCAS are present in the solid dispersion in a weight-by-weight ratio of ARN-509:HPMCAS in a range of from 1:1 to 1:5. 
     
     
         4 . The solid dispersion according to  claim 3  wherein the weight-by-weight ratio of ARN-509:HPMCAS in the solid dispersion is 1:3. 
     
     
         5 . The solid dispersion according to  claim 3  wherein the weight-by-weight ratio of ARN-509:HPMCAS in the solid dispersion is 1:2. 
     
     
         6 . The solid dispersion according to  claim 3  wherein the weight-by-weight ratio of ARN-509:HPMCAS in the solid dispersion is 1:1. 
     
     
         7 . The solid dispersion according to  claim 1  wherein ARN-509 is present in an amorphous form. 
     
     
         8 . The solid dispersion according to  claim 1  wherein the dispersion is a solid solution. 
     
     
         9 . The solid dispersion according to  claim 1  wherein the HPMCAS is HPMCAS LG. 
     
     
         10 . The solid dispersion according to  claim 1  obtainable by spray drying. 
     
     
         11 . The solid dispersion according to  claim 1  obtainable by hot melt extrusion. 
     
     
         12 . The solid dispersion according to  claim 1  wherein the HPMCAS is HPMCAS LG or HPMCAS LF and the weight-by-weight ratio of ARN-509:HPMCAS LG or HPMCAS LF in the solid dispersion is 1:2 or 1:3. 
     
     
         13 . A particle consisting of the solid dispersion as defined in  claim 1 . 
     
     
         14 . The particle according to  claim 13  wherein the HPMCAS is HPMCAS LG or HPMCAS LF and the weight-by-weight ratio of ARN-509:HPMCAS LG or HPMCAS LF in the solid dispersion is 1:2 or 1:3. 
     
     
         15 . A particle comprising the solid dispersion as defined in  claim 2 . 
     
     
         16 . A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the solid dispersion according to  claim 1 . 
     
     
         17 . The pharmaceutical formulation according to  claim 16  wherein the HPMCAS is HPMCAS LG or HPMCAS LF and the weight-by-weight ratio of ARN-509:HPMCAS LG or HPMCAS LF in the solid dispersion is 1:2 or 1:3. 
     
     
         18 . The pharmaceutical formulation according to  claim 16  wherein the formulation comprises 60 mg of ARN-509. 
     
     
         19 . The pharmaceutical formulation according to  claim 16  wherein the formulation comprises 120 mg of ARN-509. 
     
     
         20 . The pharmaceutical formulation according to  claim 16  wherein the formulation comprises 240 mg of ARN-509. 
     
     
         21 . The pharmaceutical formulation according to  claim 16  wherein the solid dispersion is present in a weight range of from 20 to 40% of the total weight of the formulation. 
     
     
         22 . The pharmaceutical formulation according to  claim 16  wherein the formulation is a tablet. 
     
     
         23 . The pharmaceutical formulation according to  claim 22  wherein the tablet is suitable for oral administration. 
     
     
         24 . A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and a plurality of particles according to  claim 13 . 
     
     
         25 . The pharmaceutical formulation according to  claim 24  wherein the HPMCAS is HPMCAS LG or HPMCAS LF and the weight-by-weight ratio of ARN-509:HPMCAS LG or HPMCAS LF in the solid dispersion is 1:2 or 1:3. 
     
     
         26 . A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the solid dispersion according to  claim 3 . 
     
     
         27 . The pharmaceutical formulation according to  claim 26  wherein the formulation comprises 60 mg of ARN-509. 
     
     
         28 . A process for preparing the solid dispersion according to  claim 10  comprising mixing ARN-509 and HPMCAS in a suitable solvent and spray drying said mixture. 
     
     
         29 . The process according to  claim 28  wherein the suitable solvent is a mixture of dichloromethane and methanol. 
     
     
         30 . The process according to  claim 29  wherein a dichloromethane and methanol are present in the mixture in a weight-by-weight ratio of 4:6.