Methods for producing an oralsuspension of teichoplanin or teichoplanin analogs

Abstract

A stable suspension of teicoplanin and one or more pharmaceutically acceptable additives and method for preparation wherein the teicoplanin is mixed with an aqueous or non aqueous suspension base and pharmaceutically acceptable additives and wherein the teicoplanin is milled to obtain a homogeneously dispersed suspension.

1 . A suspension comprising: (1) teicoplanin dispersed in an aqueous base; (2) at least one dispersing agent selected from the group comprising colloidal silicon dioxide, polyoxamer 407 or combinations thereof, (3) at least one buffering agent selected from the group comprising sodium bicarbonate, potassium bicarbonate, magnesium hydroxide, magnesium lactate, magnesium gluconate, aluminum hydroxide, tribasic sodium phosphate, anhydrous sodium carbonate, glycine, citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium polyphosphate, potassium polyphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium salts, lactates, phosphates, tartrates or combinations thereof, and (4) at least one suspension vehicle selected from the group comprising sorbitol, glycerol polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellose, hydroxypropylmethylcellulose or combinations thereof. 
     
     
         2 . The suspension of  claim 1  further comprising at least one additive selected from the group comprising sorbitol, sucrose, sodium saccharin, sodium cyclamate, aspartame, sucralose, thaumatin, acesulfam K, stevioside, monosaccharides, disaccharides, polysaccharides xylose, ribose, glucose, mannose, galactose, fructose, dextrose, sucrose, maltose, partially hydrolyzed starch, corn syrup, sorbitol, xylitol, mannitol, glycerin, synthetic flavor oil, aromatic plant extract, sunflower oil, coconut oil or combinations thereof. 
     
     
         3 . The suspension of  claim 1  wherein the pH of the suspension is from about 2 to about 8. 
     
     
         4 . The suspension of  claim 1  wherein the viscosity of the suspension is from about 20 Cps to about 500 Cps. 
     
     
         5 . The suspension of  claim 1  wherein the d90 of teicoplanin is less than about 170 μm. 
     
     
         6 . A suspension comprising: (1) teicoplanin dispersed in a non aqueous base; (2) at least one dispersing agent selected from the group comprising colloidal silicon dioxide, polyoxamer 407 or combinations thereof; and (3) at least one suspension vehicle selected from the group comprising sorbitol, glycerol, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellose, hydroxypropylmethylcellulose or combinations thereof. 
     
     
         7 . The suspension of  claim 6  further comprising at least one additive selected from the group comprising sorbitol, sucrose, sodium saccharin, sodium cyclamate, aspartame, sucralose, thaumatin, acesulfam K, stevioside, monosaccharides, disaccharides, polysaccharides xylose, ribose, glucose, mannose, galactose, fructose, dextrose, sucrose, maltose, partially hydrolyzed starch, corn syrup, sorbitol, xylitol, mannitol, glycerin, synthetic flavor oil, aromatic plant extract, sunflower oil, coconut oil or combinations thereof. 
     
     
         8 . The suspension of  claim 6  wherein the pH of the suspension is from about 2 to about 8. 
     
     
         9 . The suspension of  claim 6  wherein the viscosity of the suspension is from about 500 Cps to about 1500 Cps. 
     
     
         10 . The suspension of  claim 6  wherein the d90 of teicoplanin is less than about 170 μm. 
     
     
         11 . A method for preparing a stable, taste-masked, ready-to-use suspension of teicoplanin wherein the said process comprises the steps of (1) dispersing teicoplanin in an aqueous base comprising (a) at least one dispersing agent selected from the group comprising colloidal silicon dioxide, polyoxamer 407 or combinations thereof, (b) at least one buffering agent selected from the group comprising sodium bicarbonate, potassium bicarbonate, magnesium hydroxide, magnesium lactate, magnesium gluconate, aluminum hydroxide, tribasic sodium phosphate, anhydrous sodium carbonate, glycine, citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium polyphosphate, potassium polyphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium salts, lactates, phosphates, tartrates, or combinations thereof, and (c) at least one suspension vehicle selected from the group comprising sorbitol, glycerol polyvinyl alcohol polyvinyl pyrrolidone, polyethylene oxide, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellose, hydroxypropylmethylcellulose or combinations thereof; and (2) further milling the suspension to obtain a homogenously dispersed teicoplanin suspension. 
     
     
         12 . The method of  claim 11  wherein the suspension further comprises at least one additive selected from the group comprising sorbitol, sucrose, sodium saccharin, sodium cyclamate, aspartame, sucralose, thaumatin, acesulfam K, stevioside, monosaccharides, disaccharides, polysaccharides xylose, ribose, glucose, mannose, galactose, fructose, dextrose, sucrose, maltose, partially hydrolyzed starch, corn syrup, sorbitol, xylitol, mannitol, glycerin, synthetic flavor oil, aromatic plant extract, sunflower oil, coconut oil or combinations thereof. 
     
     
         13 . The method of  claim 11  wherein the pH of the suspension is from about 2 to about 8. 
     
     
         14 . The method of  claim 11  wherein the viscosity of the suspension is from about 20 Cps to about 500 Cps. 
     
     
         15 . The method of  claim 11  wherein the d90 of teicoplanin is less than about 170 μm. 
     
     
         16 . A method for preparing a stable, taste-masked, ready-to-use suspension of teicoplanin wherein the said process comprises the steps of (1) dispersing teicoplanin in a non aqueous base comprising at least one dispersing agent selected from the group comprising colloidal silicon dioxide, polyoxamer 407 or combinations thereof and (2) further milling the suspension to obtain a homogenously dispersed teicoplanin suspension. 
     
     
         17 . The method of  claim 16  wherein the suspension further comprises at least one additive selected from the group comprising sorbitol, sucrose, sodium saccharin, sodium cyclamate, aspartame, sucralose, thaumatin, acesulfam K, stevioside, monosaccharides, disaccharides, polysaccharides xylose, ribose, glucose, mannose, galactose, fructose, dextrose, sucrose, maltose, partially hydrolyzed starch, corn syrup, sorbitol, xylitol, mannitol, glycerin, synthetic flavor oil, aromatic plant extract, sunflower oil, coconut oil or combinations thereof. 
     
     
         18 . The method of  claim 16  wherein the pH of the suspension is from about 2 to about 8. 
     
     
         19 . The method of  claim 16  wherein the viscosity of the suspension is from about 500 Cps to about 1500 Cps. 
     
     
         20 . The method of  claim 16  wherein the d90 of teicoplanin is less than about 170 μm.