Pharmaceutical suspensions for bismuth subsalicylates

Abstract

The invention is directed to pharmaceutical compositions for suspending bismuth subsalicylate and methods of use thereof. Formulations of the present invention include at least three-gum systems to prevent the settling out of heavy particles in solution and do not include magnesium aluminum silicate. The pharmaceutical compositions may be used to treat gastrointestinal disorders.

1 . A pharmaceutical composition comprising:
 a) bismuth subsalicylate;   b) microcrystalline cellulose;   c) xanthan gum; and   d) an excipient selected from the group consisting of: carboxymethyl cellulose, carrageenan, and hydroxyethyl cellulose, or combinations thereof.   
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein said excipient is hydroxyethyl cellulose. 
     
     
         4 . The composition of  claim 1 , wherein said composition comprises bismuth subsalicylate in an amount of from about 10 mg/mL to about 60 mg/mL. 
     
     
         5 - 9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein said composition comprises bismuth subsalicylate in an amount of about 52.5 mg/mL. 
     
     
         11 . The composition of  claim 1 , wherein said composition comprises carboxymethyl cellulose and hydroxyethyl cellulose. 
     
     
         12 . The composition of  claim 1 , wherein said composition comprises xanthan gum in an amount of from about 0.50 mg/mL to about 5.0 mg/mL. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . The composition of  claim 1 , wherein said composition comprises hydroxyethyl cellulose in an amount of from about 0.45 mg/mL to about 2.0 mg/mL. 
     
     
         17 . (canceled) 
     
     
         18 . The composition of  claim 1 , wherein said composition comprises a mixture of carboxymethyl cellulose and microcrystalline cellulose. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The composition of  claim 18 , wherein the mixture of carboxymethyl cellulose and microcrystalline cellulose is present in an amount of about 17.1 mg/mL. 
     
     
         22 . (canceled) 
     
     
         23 . The composition of  claim 21 , wherein the ratio of the mixture of carboxymethyl cellulose and microcrystalline cellulose to xanthan gum is from about 2:1 to about 20:1. 
     
     
         24 . (canceled) 
     
     
         25 . The composition of  claim 1 , wherein said composition has a sedimentation rate of from about 0.001 mm/day to about 0.015 mm/day at 23° C. as determined by x-ray measurement. 
     
     
         26 . (canceled) 
     
     
         27 . The composition of  claim 1 , wherein said composition has a viscosity of from about 800 cps to about 2400 cps. 
     
     
         28 . (canceled) 
     
     
         29 . The composition of  claim 1 , wherein the pH of the composition is from about 4.0 to about 5.5. 
     
     
         30 - 31 . (canceled) 
     
     
         32 . A pharmaceutical composition comprising:
 a) bismuth subsalicylate;   b) xanthan gum;   c) hydroxyethyl cellulose; and   d) a mixture of microcrystalline cellulose and carboxymethyl cellulose.   
     
     
         33 . The composition of  claim 32 , wherein the ratio of the mixture of microcrystalline cellulose and carboxymethyl cellulose to hydroxyethyl cellulose is from about 6:1 to about 250:1. 
     
     
         34 . (canceled) 
     
     
         35 . The composition of  claim 32 , wherein the ratio of the mixture of microcrystalline cellulose and carboxymethyl cellulose to xanthan gum is from about 5:1 to about 13:1. 
     
     
         36 - 43 . (canceled) 
     
     
         44 . A method of treating a gastrointestinal disorder in a patient in need thereof, comprising administering to the patient a composition comprising:
 a) bismuth subsalicylate;   b) microcrystalline cellulose;   c) xanthan gum; and   d) an excipient selected from the group consisting of: carboxymethyl cellulose, carrageenan, and hydroxyethyl cellulose, or combinations thereof.   
     
     
         45 - 54 . (canceled) 
     
     
         55 . The method of  claim 44 , wherein said composition comprises xanthan gum in an amount of from about 0.50 mg/mL to about 5.0 mg/mL. 
     
     
         56 - 66 . (canceled) 
     
     
         67 . The method of  claim 44 , wherein said composition has a viscosity of from about 800 cps to about 2400 cps. 
     
     
         68 - 69 . (canceled) 
     
     
         70 . A process for producing a composition of  claim 1 , comprising:
 forming a gum premix comprising glycerin, simethicone, hydroxyethyl cellulose, and xanthan gum in a first vessel;   forming a dye premix comprising an aqueous mixture of dye compounds in a second vessel;   forming a third mixture comprising water, microcrystalline cellulose, carboxymethyl cellulose, and bismuth subsalicylate in a third vessel; and   combining the gum premix, dye premix and third mixture together to produce the composition.   
     
     
         71 - 85 . (canceled)