Formulations of nebivolol
View Patent ↗Formulations of Nebivolol are provided. One formulation includes 0.05 to 10% (w/w) of Nebivolol or a pharmaceutically acceptable salt thereof, 0.4 to 10% (w/w) of a solubilizer, and 5 to 90% (w/w) of a sweetener. The formulation has a pH in the range of 3 to 7. A reconstituted formulation including the formulation with a liquid vehicle is also provided. Also provided are processes of preparing the formulations.
1 . A formulation of powder for oral solution, said formulation comprising:
a. from 0.05 to 10% (w/w) of nebivolol hydrocholoride as the sole active agent;
b. from 0.4 to 10% (w/w) of a solubilizer selected from cyclodextrin, propylene glycol, polyethylene glycol, polysorbate 20, polysorbate 80, sorbitan monooleate, poloxamer, and sodium lauryl sulfate;
c. from 5 to 90% (w/w) of one or more sweetener selected from the group consisting of glucose, fructose, sucrose, xylitol, tagatose, sucralose, maltitol, isomaltulose, isomaltulose, lactitol, sorbitol, erythritol, trehalose, maltodextrin, polydextrose, inulin, erythritol, acesulfame, and salts thereof, alitame, aspartame, neotame, sodium cyclamate, saccharin and salts thereof; and
d. from 0.05 to 20% (w/w) of a preservative selected from the group consisting of ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, sodium benzoate, sodium bisulfate, sodium metabisulfite, sodium sulfite, methyl paraben, propylparaben, benzoic acid, potassium sorbate, and combinations thereof,
wherein upon reconstitution with a liquid vehicle selected from the group consisting of water, ethyl alcohol, syrup, beverage, juices, and combinations thereof, the liquid formulation obtained has a pH from 3 to 7 and;
has less than 1% (w/w) of impurities at the end of storage for at least 30 days.
2 . The formulation as claimed in claim 1 , further comprising one or more of a flavouring agent in the weight range of from 0.05 to 20% (w/w) of the formulation, wherein the flavouring agent is selected from the group consisting of an almond, anise, apple, apricot, banana, blackberry, blackcurrant, blueberry, caramel, cherry, chocolate, cinnamon, cranberry, grape, lemon, lime, orange, peppermint, pineapple, raspberry, spearmint, strawberry, vanilla, bubble gum and tutti-frutti flavouring agent;
a buffering agent in the weight range of from 0.025 to 15% (w/w) of the formulation, wherein the buffering agent is selected from the group consisting of citric acid, sodium citrate, sodium tartarate, sodium acetate, sodium carbonate, sodium polyphosphate, potassium polyphosphate, sodium pyrophosphate, potassium pyrophosphate, disodium hydrogenphosphate, trisodium phosphate, sodium phosphate, tripotassium phosphate, sodium acetate, potassium metaphosphate, magnesium oxide, magnesium carbonate, magnesium silicate, calcium acetate, calcium glycerophosphate, calcium chloride, calcium hydroxide, calcium lactate, calcium carbonate, and calcium bicarbonate;
a glidant in the weight range of from 0.1 to 3.0% (w/w) of the formulation wherein the glidant is selected from the group consisting of calcium phosphate tribasic, calcium silicate, cellulose powder, colloidal silicon dioxide, magnesium silicate, magnesium trisilicate, silicon dioxide, starch and talc; and
a coloring agent in the weight range of from 0.01 to 2% (w/w) of the formulation, wherein the coloring agent is selected from the group consisting of FD&C Red No. 3, FD&C Red No. 20, FD&C Red No. 40, FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green No. 5, D&C Orange No. 5, D&C Yellow No. 10, caramel, ferric oxide and combinations thereof.
3 . The formulation as claimed in claim 1 , wherein the formulation reconstituted in the liquid vehicle comprises from 0.1 to 50 mg/ml of nebivolol hydrochloride; from 0.1 to 300 mg/ml of the solubilizer; and from 5 to 400 mg/ml of the sweetener.
4 . The formulation as claimed in claim 1 , wherein the liquid formulation obtained by reconstitution comprises from 0.1 ml to 50 ml of the liquid vehicle.
5 . A powder formulation for oral solution comprising:
a. from 0.1 to 1% (w/w) of nebivolol hydrochloride as the sole active agent;
b. from 4 to 10% (w/w) of sodium lauryl sulfate;
c. from 7 to 90% (w/w) of sorbitol;
d. from 0.5 to 1% (w/w) of sodium benzoate,
e. from 1 to 5% (w/w) of a flavoring agent,
wherein upon reconstitution with 0.1 to 50 ml of a liquid vehicle selected from the group consisting of water, ethyl alcohol, syrup, beverage, juices, or combinations thereof, the liquid formulation obtained has a pH in the range of 3 to 7 and has less than 1% (w/w) of impurities at the end of storage for at least 30 days.