Liquid oral formulations for PDE V inhibitors
The present disclosure is directed to pharmaceutical compositions comprising a PDE V inhibitor and one or more pharmaceutical excipients or additives wherein the pharmaceutical compositions are in the form of liquid pharmaceutical compositions. The pharmaceutical compositions of the present disclosure are useful for the treatment of diseases or conditions which are treatable by administration of PDE V inhibitor drug such as pulmonary arterial hypertension, erectile dysfunction, etc.
1 . A liquid oral pharmaceutical composition comprising:
about 4 mg/mL tadalafil or a pharmaceutically acceptable salt thereof, wherein the tadalafil comprises particulate tadalafil having a d90 particulate size of from about 5 microns to about 200 microns;
means for maintaining the particulate tadalafil uniformly dispersed in a liquid vehicle, which comprises a viscosity modifying agent that comprises xanthan gum in an amount of from about 2 mg/mL to about 6 mg/ml;
means for maintaining the composition at a pH of from about 4 to about 8; and
a vehicle comprising water.
2 . The liquid oral pharmaceutical composition of claim 1 , wherein the tadalafil comprises particulate tadalafil having a d90 particulate size of from about 5 microns to about 100 microns.
3 . The liquid oral pharmaceutical composition of claim 1 , wherein the tadalafil comprises particulate tadalafil having a d90 particulate size of from about 5 microns to about 50 microns.
4 . The liquid oral pharmaceutical composition of claim 1 , wherein the tadalafil comprises particulate tadalafil having a d90 particulate size of from about 5 microns to about 20 microns.
5 . The liquid oral pharmaceutical composition of claim 1 , wherein the tadalafil comprises particulate tadalafil having a d90 particulate size of about 8 microns.
6 . The liquid oral pharmaceutical composition of claim 5 , wherein the means for maintaining the particulate tadalafil uniformly dispersed comprises a viscosity modifying agent in an amount of from about 2 mg/mL to about 6 mg/mL.
7 . The liquid oral pharmaceutical composition of claim 1 , wherein the means for maintaining the composition at a pH comprises a buffering agent.
8 . The liquid oral pharmaceutical composition of claim 7 , wherein the buffering agent comprises citric acid, tri-sodium citrate, sodium citrate, citric acid monohydrate, tri-sodium citrate dihydrate, potassium phosphate, sodium phosphate, or a combination thereof.
9 . The liquid oral pharmaceutical composition of claim 7 , wherein the buffering agent comprises citric acid and tri-sodium citrate.
10 . The liquid oral pharmaceutical composition of claim 9 , wherein the citric acid is present in an amount of from about 2 mg/mL to about 4 mg/mL and the tri-sodium citrate is present in an amount of from about 3 mg/mL to about 6 mg/mL.
11 . The liquid oral pharmaceutical composition of claim 6 , wherein the means for maintaining the composition at a pH comprises a buffering agent.
12 . The liquid oral pharmaceutical composition of claim 1 , wherein the liquid oral pharmaceutical composition has a pH of from about 4.5 to about 5.5.
13 . The liquid oral pharmaceutical composition of claim 1 , wherein the liquid oral pharmaceutical composition has a pH of about 5.
14 . The liquid oral pharmaceutical composition of claim 11 , wherein the liquid oral pharmaceutical composition has a pH of about 5.
15 . The liquid oral pharmaceutical composition of claim 1 , further comprising a preservative.
16 . The liquid oral pharmaceutical composition of claim 15 , wherein the preservative comprises sodium benzoate, methylparaben, propylparaben, potassium benzoate, potassium sorbate, sorbic acid, benzoic acid, or a combination thereof.
17 . The liquid oral pharmaceutical composition of claim 14 , further comprising a preservative.
18 . The liquid oral pharmaceutical composition of claim 1 , further comprising a sweetener.
19 . The liquid oral pharmaceutical composition of claim 1 , further comprising a flavorant.
20 . The liquid oral pharmaceutical composition of claim 1 , further comprising a preservative, a sweetener, and a flavorant.
21 . A method for treating pulmonary arterial hypertension, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 1 .
22 . A method for treating erectile dysfunction, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 1 .
23 . A method for treating benign prostatic hyperplasia, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 1 .
24 . A method for treating pulmonary arterial hypertension, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 17 .
25 . A method for treating erectile dysfunction, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 17 .
26 . A method for treating benign prostatic hyperplasia, which comprises administering to a human patient in need thereof a therapeutically effective amount of the liquid oral pharmaceutical composition of claim 17 .