Pharmaceutical formulations for the treatment of overactive bladder

Abstract

Disclosed herein are pharmaceutical compositions comprising a plurality of first beads each comprising: a core; a first layer comprising pilocarpine or a pharmaceutically acceptable salt thereof; and a second layer comprising a first polymer. Also disclosed are pharmaceutical compositions comprising a plurality of second beads each comprising: a core; and a first layer comprising tolterodine or a pharmaceutically acceptable salt thereof. Further disclosed are pharmaceutical formulations comprising: a) a plurality of the first beads; b) a plurality of the second beads; or c) a plurality of the first beads and a plurality of the second beads.

1 . A pharmaceutical composition comprising:
 a) a plurality of first beads each comprising:   a microcrystalline cellulose bead core,   a first layer comprising pilocarpine, or a pharmaceutically acceptable salt thereof, and hydroxypropylmethylcellulose, and   a second layer comprising one or both of hydroxypropylcellulose and ethylcellulose; and   b) a plurality of second beads each comprising:   a microcrystalline cellulose bead core,   a first layer comprising tolterodine, or a pharmaceutically acceptable salt thereof, hydroxypropylmethylcellulose, and polyethylene glycol,   wherein the plurality of first beads release less than 20% of the pilocarpine, or a pharmaceutically acceptable salt thereof, when immersed for 20 minutes in 0.1 N HCl.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the first bead core comprises between about 10% to about 50% of the total weight of the finally-formulated bead. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the first layer of the first bead comprises between about 5% to about 30% of the total weight of the bead. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the first bead coated with the first layer comprises an amount of pilocarpine that provides a dose of between 3 mg and 12 mg of pilocarpine per pharmaceutical composition. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the first layer of the first bead comprises hydroxypropylmethylcellulose in about between about 2% to about 40% of the total weight of the bead. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the second layer comprises both hydroxypropylcellulose and ethylcellulose, and the weight ratio of hydroxypropylcellulose to ethylcellulose is between about 5:1 to about 1:5 by weight. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the second layer comprises hydroxypropylcellulose in about between about 5% to about 40% of the total weight of the bead. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the second layer comprises ethylcellulose in about between about 5% to about 40% of the total weight of the bead. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the second bead core comprises between about 25% to about 85% of the total weight of the finally-formulated bead. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the first layer of the second bead comprises between about 2% to about 25% of the total weight of the bead. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the second bead coated with the first layer comprises an amount of tolterodine tartrate that provides a dose of between 1 mg and 6 mg of tolterodine per pharmaceutical composition. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the second bead coated with the first layer comprises hydroxypropylmethylcellulose in between about 5% to about 15% of the total weight of the bead. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the second bead further comprises a de-tackifier or a glidant. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the addition of the second layer to the first bead represents a weight gain selected from the group consisting 75%, 100%, 125%, 150%, 175%, 200%, and 250%. 
     
     
         15 . A pharmaceutical composition comprising a plurality of first beads each comprising:
 a microcrystalline cellulose bead core, wherein the bead core comprises between about 15% to about 40% of the total weight of the finally-formulated bead;   a first layer comprising pilocarpine, or a pharmaceutically acceptable salt thereof, and hydroxypropylmethylcellulose, wherein the first layer comprises between about 5% to about 15% of the total weight of the finally-formulated bead;   a second layer comprising one or both of hydroxypropylcellulose and ethylcellulose, wherein the weight of the second layer is between about 75% to about 250% of the weight of the bead prior to the application of the second layer;   wherein the plurality of first beads release less than 20% of the pilocarpine, or a pharmaceutically acceptable salt thereof, when immersed for 20 minutes in 0.1 N HCl.   
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the pilocarpine is pilocarpine hydrochloride. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein the second layer comprises both hydroxypropylcellulose and ethylcellulose, and the weight ratio of hydroxypropylcellulose to ethylcellulose is between about 5:1 to about 1:5 by weight. 
     
     
         18 . A pharmaceutical composition comprising a plurality of beads each comprising:
 a microcrystalline cellulose bead core, wherein the core comprises between about 40% to about 80% of the total weight of the finally-formulated bead;   a first layer comprising tolterodine, or a pharmaceutically acceptable salt thereof, hydroxypropylmethylcellulose, and polyethylene glycol, wherein the first layer comprises between about 4% to about 25% of the total weight of the finally-formulated bead.   
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the tolterodine is tolterodine tartrate.