HYDROCHLOROTHIAZIDE COMPOSITIONS
Disclosed herein is a powder for oral suspension and a reconstituted product therein comprising highly pure hydrochlorothiazide, which is useful for treating hypertension and edema.
1 . A powder for oral suspension for oral administration, comprising
about 3% w/w to about 5% w/w of hydrochlorothiazide;
at least one thickening agent; and
at least one pharmaceutically acceptable excipient;
wherein the powder for oral suspension composition in 5 mL of water has a pH of from about 2.5 to about 4.5.
2 . The powder of claim 1 comprising about 3.8% w/w to about 4.4% w/w of hydrochlorothiazide.
3 . The powder of claim 1 comprising about 4.2% w/w of hydrochlorothiazide.
4 . The powder of claim 1 having a water content of not more than about 0.8% w/w.
5 . The powder of claim 1 , wherein at least one thickening agent selected from hydrocolloid gum, cellulosic derivative, a polysaccharide, alginate, acrylic acid copolymer, polyvinylpyrrolidone, aluminium magnesium silicate, and a combination thereof.
6 . The powder of claim 1 , wherein the amount of thickening agent in an amount of from about 0.4% w/w to about 5% w/w.
7 . The powder of claim 1 , wherein the thickening agent comprises xanthan gum in an amount of from about 0.4% w/w to about 2.0% w/w.
8 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a preservative and a sweetener.
9 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a preservative selected from the group consisting of sodium benzoate, benzoic acid, potassium sorbate, paraben, methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, benzyl alcohol, boric acid, calcium acetate, bentonite, cetrimide, chlorhexidine, cetylpyridinium chloride, cresol, chlorbutanol, magnesium trisilicate, and a combination thereof
10 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a preservative selected from the group consisting of sodium benzoate, benzoic acid, potassium sorbate, paraben, methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, benzyl alcohol, boric acid, calcium acetate, bentonite, cetrimide, chlorhexidine, cetylpyridinium chloride, cresol, chlorbutanol, magnesium trisilicate, and combination thereof in an amount of from about 0.01% w/w to about 5% w/w.
11 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a sweetener selected from the group consisting of sucralose, maltilol, liquid glucose, magnasweet 110, magnasweet 180, saccharin sodium, xylitol, sorbitan monoleate, sorbitol, sucrose, aspartame, acesulfame potassium, and a combination thereof.
12 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a sweetener selected from the group consisting of sucralose, maltilol, liquid glucose, magnasweet 110, magnasweet 180, saccharin sodium, xylitol, sorbitan monoleate, sorbitol, sucrose, aspartame, acesulfame potassium, and a combination thereof in an amount of from about 0.1% w/w to about 96% w/w.
13 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a sweetener selected from the group consisting of sucralose, sucrose, and a combination thereof in an amount of from about 90% w/w to about 96% w/w.
14 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a pH modifier selected from group consisting of citric acid, fumaric acid, tartaric acid, malic acid, sodium phosphate monobasic, potassium phosphate, maleic acid, lactic acid, hydrochloric acid, phosphoric acid, and a combination thereof
15 . The powder of claim 1 , wherein the at least one pharmaceutically acceptable excipient comprises a pH modifier selected from group consisting of citric acid, fumaric acid, tartaric acid, malic acid, sodium phosphate monobasic, potassium phosphate, maleic acid, lactic acid, hydrochloric acid, phosphoric acid, and a combination thereof in an amount of from about 0.2% w/w to about 1.2% w/w.
16 . The powder of claim 1 , having a salamide impurity content not more than 1.0% for at least about 6-months when stored at 25±2° C. and 60±5% relative humidity, 40° C. and 75% relative humidity and a salamide impurity content not more than 1.0% for at least about 6-months when stored at 25±2° C. and 60±5% relative humidity after reconstitution.
17 . An oral liquid suspension comprising the powder of claim 1 a pharmaceutically acceptable carrier comprising water.
18 . The oral liquid suspension of claim 17 having a volume of from about 50 mL to about 150 mL.
19 . A method of treating edema and hypertension comprising administering to a patient in need thereof a therapeutically effective amount of the oral liquid suspension of claim 17 .
20 . The method of claim 19 , wherein administration of the oral liquid suspension to the human patient provides a geometric least squares mean for C max of from about 300 ng/mL to about 400 ng/mL, a geometric least squares mean for AUC 0-∞ of from about 2200 ng●hr/mL to about 2500 ng●hr/mL, or a combination thereof.