Formulations of Nebivolol
The present disclosure provides a formulation comprising: 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, wherein the formulation has pH in the range of 3 to 7. The present disclosure provides a reconstituted formulation comprising the formulation with a liquid vehicle. The present disclosure also provides process of preparing the formulations and methods thereof.
1 . An oral liquid formulation comprising:
a. 0.1 to 2% (w/w) of nebivolol hydrochloride as the sole active ingredient;
b. 5 to 10% (w/w) of a solubilizer selected from the group consisting of cyclodextrin, propylene glycol, polyethylene glycol, polysorbate 20, polysorbate 80, sorbitan monooleate, poloxamer, sodium lauryl sulfate and mixtures thereof;
c. 70 to 90% (w/w) of one or more sweeteners selected from the group consisting of glucose, fructose, sucrose, xylitol, tagatose, sucralose, maltitol, isomaltulose, lactitol, sorbitol, erythritol, trehalose, maltodextrin, polydextrose, inulin, acesulfame, alitame, aspartame, neotame, sodium cyclamate, saccharin and mixtures thereof;
d. 0.5 to 1% (w/w) of a preservative selected from the group consisting of ascorbic acid, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, sodium benzoate, sodium bisulfate, sodium metabisulfite, sodium sulfite, methyl paraben, propylparaben, benzoic acid, potassium sorbate, and mixtures thereof; and
e. a liquid vehicle selected from the group consisting of water, ethyl alcohol, syrup and mixtures thereof;
wherein the formulation has a pH in the range of from 3 to 7 and the formulation has less than 1% (w/w) of each of the desfluoro nebivolol and 4-benzylated nebivolol impurities, when stored at a temperature of about 25±5° C. for a time period in the range of from 30 days to one year.
2 . The oral liquid formulation of claim 1 , wherein the formulation comprises from 0.1 to 50 ml of the vehicle.
3 . The oral liquid formulation of claim 1 , further comprising from 0.1 to 1% (w/w) of a flavouring agent.
4 . The oral liquid formulation of claim 3 , wherein the flavouring agent is selected from the group consisting of strawberry, cherry, grape, orange, peppermint, vanilla, bubble gum, and mixtures thereof.
5 . The oral liquid formulation of claim 1 , further comprising from 0.025 to 5% of a buffer.
6 . The oral liquid formulation of claim 5 , wherein the buffer 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.
7 . The oral liquid formulation of claim 1 , wherein the formulation has less than 5% (w/w) of total impurities, when stored at about 25±5° C. for a time period in the range of from 30 days to one year.