Solid molecular dispersion of fesoterodine hydrogen fumarate and polymeric binder

Abstract

The present invention relates to solid molecular dispersion of fesoterodine hydrogen fumarate and a polymeric binder. The invention also relates to an inert core bead or particle which is coated with said solid molecular dispersion and to pharmaceutical formulations comprising such coated beads or particles.

1 . A solid molecular dispersion comprising from 3:97 to 12:88 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         2 . A solid dispersion comprising from 3:97 to 12:88 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof, in which the fesoterodine hydrogen fumarate is stabilised in the dispersion in a form not corresponding to its crystalline or amorphous form. 
     
     
         3 . A dispersion as claimed in  claim 1  or  2  comprising about a 1:9 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         4 . A dispersion as claimed in  claim 3  consisting essentially of about a 1:9 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         5 . A dispersion as claimed in  claim 1  or  2  comprising about a 1:19 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         6 . A dispersion as claimed in  claim 5  consisting essentially of about a 1:19 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         7 . A dispersion as claimed in  claim 1  or  2  consisting essentially of fesoterodine hydrogen fumarate, and an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof. 
     
     
         8 . A dispersion as claimed in any one of  claims 1  to  7  wherein the cellulose ether component is selected from hydroxypropyl methyl cellulose (HPMC), hydroxyethyl methyl cellulose (HEMC), hydroxybutyl methyl cellulose (HBMC), hydroxyethylcellulose (HEC), hydroxypropyl cellulose (HPC) or hydroxypropyl methyl cellulose acetate succinate (HPMCAS): or is a mixture of any two or more thereof. 
     
     
         9 . A dispersion as claimed in  claim 8  wherein the cellulose ether component is hydroxypropyl methyl cellulose alone. 
     
     
         10 . A dispersion as claimed in any one of  claims 1  to  9  for use as a medicament. 
     
     
         11 . A dispersion as claimed in any one of  claims 1  to  9  for use in the treatment of urinary incontinence. 
     
     
         12 . An inert core bead or particle which is coated with a dispersion as claimed in any one of  claims 1  to  9 . 
     
     
         13 . An inert core bead or particle as claimed in  claim 12  wherein the core bead or particle comprises microcrystalline cellulose 
     
     
         14 . An inert core bead or particle as claimed in  claim 12  wherein the core bead or particle comprises lactose. 
     
     
         15 . An inert core bead or particle as claimed in  claim 13  which is further coated with a modified-release layer. 
     
     
         16 . An inert core bead or particle as claimed in  claim 15  wherein the modified release layer comprises ethyl cellulose and hydroxypropyl cellulose. 
     
     
         17 . An inert core bead or particle as claimed in any one of  claims 12  to  16  for use as a medicament. 
     
     
         18 . An inert core bead or particle as claimed in any one of  claims 12  to  16  for use in the treatment of urinary incontinence. 
     
     
         19 . A pharmaceutical formulation comprising modified-release beads as claimed in  claim 15  or  16 . 
     
     
         20 . A formulation as claimed in  claim 19  wherein the said modified-release beads are encapsulated. 
     
     
         21 . A pharmaceutical tablet formulation comprising an inert core bead or particle as claimed in  claim 14 . 
     
     
         22 . A formulation as claimed in any one of  claims 19  to  21  for use as a medicament. 
     
     
         23 . A formulation as claimed in any one of  claims 19  to  21  for use in the treatment of urinary incontinence. 
     
     
         24 . A solid dispersion comprising from 3:97 to 12:88 weight % ratio of fesoterodine hydrogen fumarate:an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof, in which the fesoterodine hydrogen fumarate is stabilised in the dispersion in a form not corresponding to its crystalline or amorphous form and which generally displays the FTIR characteristics shown in  FIG. 3, 3   a ,  4 ,  4   a ,  5 ,  5   a ,  7 ,  7   a ,  8  or  8   a.    
     
     
         25 . A solid molecular dispersion obtainable by (a) achieving a solution of fesoterodine hydrogen fumarate and an alkyl hydroxyalkylcellulose ether or a hydroxyalkylcellulose ether, or an ester of either thereof, or a mixture of any two or more thereof, in from 3:97 to 12:88 weight % ratio, and (b) by drying to form said dispersion.