# US 12,005,062 B2 · Liquid oral formulations for sildenafil > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,062 B2 - Document ID: US12005062B2 - Status: Granted - Kind: B2 - Application number: 18/365,266 - Filed: 2023-08-04 - Published: 2023-11-30 - Granted: 2024-06-11 - Earliest claimed: 2017-12-26 - Assignees: Liqmeds Worldwide Limited - Applicants: Liqmeds Worldwide Limited - Inventors: Jinal Pandya; Sandip P. Mehta; Manish Umrethia; Jayanta Kumar Mandal; Hiren Pansuriya - Web page: https://patentgrep.com/patent/US12005062B2 ## CPC - A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract 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. ## Claims ### Claim 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. ### Claim 2 (depends on 1) The ready-to-use liquid oral formulation of claim 1 having a pH of from about 4 to about 8. ### Claim 3 (depends on 1) The ready-to-use liquid oral formulation of claim 1 having a pH of from about 4 to about 6. ### Claim 4 (depends on 1) The ready-to-use liquid oral formulation of claim 1 having a pH of about 5. ### Claim 5 (depends on 1) The ready-to-use liquid oral formulation of claim 1, wherein the one or more pharmaceutically acceptable excipients further comprises a buffering agent. ### Claim 6 (depends on 1) 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. ### Claim 7 (depends on 1) 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. ### Claim 8 (depends on 1) 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. ### Claim 9 (depends on 1) 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. ### Claim 10 (depends on 1) 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. ### Claim 11 (depends on 1) 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. ### Claim 12 (depends on 1) 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. ### Claim 13 (depends on 1) 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. ### Claim 14 (depends on 1) 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. ### Claim 15 (depends on 1) The ready-to-use liquid oral formulation of claim 1, wherein the wetting agent comprises glycerin in an amount of about 400 mg/mL. ### Claim 16 (depends on 1) 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. ### Claim 17 (depends on 1) 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. ### Claim 18 (depends on 1) 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. ### Claim 19 (depends on 1) The ready-to-use liquid oral formulation of claim 1, wherein the one or more pharmaceutically acceptable excipients further comprises a viscosity modifying agent. ### Claim 20 (depends on 1) 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. ### Claim 21 (depends on 1) 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. ### Claim 22 (depends on 1) 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. ### Claim 23 (depends on 1) 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. ### Claim 24 (depends on 1) 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. ### Claim 25 (depends on 1) 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. ### Claim 26 (depends on 1) 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%. ### Claim 27 (depends on 1) 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. ### Claim 28 (depends on 1) 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. ### Claim 29 (depends on 1) 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. ### Claim 30 (depends on 1) 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.