Liquid oral formulations for sildenafil
The present disclosure is directed to pharmaceutical compositions comprising sildenafil or a pharmaceutically acceptable salt thereof 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 sildenafil or a pharmaceutically acceptable salt thereof such as pulmonary arterial hypertension, erectile dysfunction, etc.
1. A ready-to-use liquid oral formulation, comprising:
about 10 mg/mL of sildenafil, as sildenafil citrate having a d90 particle size of from about 10 microns to about 100 microns; and
one or more pharmaceutically acceptable excipients comprising a wetting agent comprising glycerin in an amount of from about 100 to about 1,000 mg/mL.
2. The ready-to-use liquid oral formulation of claim 1 having a pH of from about 4 to about 8.
3. The ready-to-use liquid oral formulation of claim 1 having a pH of from about 4 to about 6.
4. The ready-to-use liquid oral formulation of claim 1 having a pH of about 5.
5. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffering agent.
6. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffering agent comprising acetic acid, adipic acid, ammonium carbonate, ammonium hydroxide, ammonium phosphate, boric acid, citric acid, citric acid, diethanolamine, fumaric acid, malic acid, propionic acid, potassium acetate, potassium bicarbonate, potassium citrate, potassium metaphosphate, potassium phosphate, sodium acetate, sodium bicarbonate, sodium borate, sodium carbonate, sodium citrate, tri-sodium citrate, sodium glycolate, sodium lactate, sodium phosphate, sodium propionate, succinic acid, tartaric acid, triethylamine, triethanolamine, tromethamine, trolamine or a combination thereof.
7. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a buffering agent comprising acetic acid, adipic acid, boric acid, citric acid, citric acid, fumaric acid, malic acid, phosphoric acid, propionic acid, succinic acid, tartaric acid, or a combination thereof.
8. The ready-to-use liquid oral formulation of claim 1 , wherein the sildenafil citrate has a d90 particle size of from 10 microns to about 50 microns.
9. The ready-to-use liquid oral formulation of claim 1 , wherein the sildenafil citrate has a d90 particle size of from about 20 microns to about 50 microns.
10. The ready-to-use liquid oral formulation of claim 1 wherein the sildenafil citrate has a d90 particle size of from about 20 microns to about 30 microns.
11. The ready-to-use liquid oral formulation of claim 1 , wherein the wetting agent comprises glycerin in an amount of from about 200 mg/mL to about 1,000 mg/mL.
12. The ready-to-use liquid oral formulation of claim 1 , wherein the wetting agent comprises glycerin in an amount of from about 200 mg/mL to about 800 mg/mL.
13. The ready-to-use liquid oral formulation of claim 1 , wherein the wetting agent comprises glycerin in an amount of from about 200 mg/mL to about 600 mg/mL.
14. The ready-to-use liquid oral formulation of claim 1 , wherein the wetting agent comprises glycerin in an amount of from about 300 mg/mL to about 500 mg/mL.
15. The ready-to-use liquid oral formulation of claim 1 , wherein the wetting agent comprises glycerin in an amount of about 400 mg/mL.
16. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises an anti-foaming agent comprising a simethicone, a simethicone emulsion, an organic phosphate, a paraffin oil, a stearate, a glycol, or a combination thereof.
17. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises an anti-foaming agent comprising a simethicone, a simethicone emulsion, an organic phosphate, a paraffin oil, a stearate, a glycol, or a combination thereof in an amount of from 0.1 mg/mL to about 100 mg/mL.
18. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises an anti-foaming agent comprising a simethicone, a simethicone emulsion, an organic phosphate, a paraffin oil, a stearate, a glycol, and a combination thereof in an amount of about 0.5 mg/mL.
19. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent.
20. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent comprising one or more water-soluble hydrocolloids.
21. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent comprising one or more water-soluble hydrocolloids in an amount of from about 1 mg/mL to about 20 mg/mL.
22. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent comprising acacia, agar, alginic acid, carbomer, carmellose sodium, dextrin, gelatin, veegum, gellan gum, sodium alginate, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropyl starch, hypromellose, maltodextrin, methylcellulose, modified starch, pectin, poloxamer, polycarbophil, polyethylene glycol, polyvinyl acetate, poly(vinyl alcohol), potassium alginate, polyvinyl pyrrolidone, pregelatinized starch, propylene glycol alginate, sodium alginate, carboxymethyl cellulose, an alkali metal carboxymethyl cellulose, microcrystalline cellulose, gum arabic, karaya gum, sterculia gum, tragacanth, xanthan gum, bentonite, carageenan, guar gum, colloidal silicon dioxide, or a combination thereof.
23. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent comprising acacia, agar, alginic acid, gelatin, gellan gum, gum arabic, karaya gum, sterculia gum, tragacanth, xanthan gum, carageenan, guar gum, or a combination thereof.
24. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises one or more preservatives comprising ethanol, chlorobutanol, phenoxyethanol, potassium benzoate, benzyl alcohol, benzoic acid, potassium sorbate, sorbic acid, benzalkonium chloride, benzethonium chloride, cetrimonium bromide, cetylpyridinium chloride, bronopol, chlorbutol, chlorocresol, cresol, butylparaben, methylparaben, propylparaben, ethylparaben, phenol, thymol, phenylethanol, sodium benzoate, or a combination thereof.
25. The ready-to-use liquid oral formulation of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprises one or more preservatives selected from potassium benzoate, benzoic acid, potassium sorbate, sorbic acid, butylparaben, methylparaben, propylparaben, ethylparaben, sodium benzoate, or a combination thereof in an amount of from 0.1 mg/mL to about 100 mg/mL.
26. The ready-to-use liquid oral formulation of claim 1 , wherein the ready-to-use liquid oral formulation is stable for up to six months when stored at 25° C. and 60% relative humidity characterized in that any individual impurity present in the composition is less than 0.2% and the total impurities present in the composition are less than 1.0%.
27. A method of treating a condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the ready-to-use liquid oral formulation of claim 1 , wherein the condition is selected from hypertension, pulmonary hypertension, arterial hypertension, pulmonary arterial hypertension, and erectile dysfunction.
28. A method of treating a condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the ready-to-use liquid oral formulation of claim 1 , wherein the condition is selected from hypertension, pulmonary hypertension, arterial hypertension, and pulmonary arterial hypertension.
29. A method of treating a condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the ready-to-use liquid oral formulation of claim 1 , wherein the condition is pulmonary arterial hypertension.
30. A method of treating a condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the ready-to-use liquid oral formulation of claim 1 , wherein the condition is erectile dysfunction.