WO2001035926A2 - An improved pharmaceutical composition for treating male erectile dysfunction - Google Patents
An improved pharmaceutical composition for treating male erectile dysfunction Download PDFInfo
- Publication number
- WO2001035926A2 WO2001035926A2 PCT/IN2000/000105 IN0000105W WO0135926A2 WO 2001035926 A2 WO2001035926 A2 WO 2001035926A2 IN 0000105 W IN0000105 W IN 0000105W WO 0135926 A2 WO0135926 A2 WO 0135926A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- pharmaceutical composition
- sildenafil
- improved pharmaceutical
- solution
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Definitions
- the present invention relates to an improved pharmaceutical composition containing sildenafil intended for nasal administration for the treatment of male erectile dysfunction due to organic, psychogenic and mixed causes.
- the composition is also particularly effective in patients with erectile dysfunction due to spinal cord injury.
- the pharmaceutical composition of the present invention may be in the form of a solution or a colloidal dispersion in a pharmaceutical vehicle.
- the composition can be filled into specially designed dosing device for nasal administration.
- Sildenafil has the chemical formula C 22 H 30 N O 4 S
- Sildenafil is potent and selective inhibitor of type V cyclic guanosine mono phosphodiestrase (cGMP) with utility for the treatment of male erectile dysfunction. Recently, it has been hypothesized that penile erections are dependent on nitric oxide (NO) and its second messenger cGMP. Sildenafil amplifies the neuronal nitric oxide (NO) / cGMP pathway implicated in the relaxation of the corpus cavernosum. The drug is well tolerated orally. Headache, dyspepsia, facial flushing and muscular ache are the common adverse events reported [Steers, W. D. et al. 2 nd Meet Eur. Soc. Impotence Res.
- cGMP cyclic guanosine mono phosphodiestrase
- sildenafil citrate (M/s Pfizer Inc.). Sildenafil citrate is soluble in dimethylformamide, sparingly soluble in acetic acid, slightly soluble in alcohol. About 3.5 mg is soluble in water.
- JP 10298062 a pharmaceutical composition in the form of tablets that rapidly soluble in the oral cavity and manufacturing procedure has been disclosed.
- WO 9830209 a rapidly releasing and taste masking pharmaceutical composition
- a core containing Sildenafil an inner coating layer formed of a water soluble polymer and an outer coating layer formed on inner coating containing saliva insoluble polymer and a process for preparing such oral dosage form
- sildenafil is administered orally about one hour before intercourse. This is a major disadvantage of the oral formulations, creating in convenience to the partners. Rapid onset of action is highly desirable in such therapeutic indication for patients.
- WO 00/00199 an intranasal dosage unit of cyclic guanosine monophosphate specific phosphodiesterase inhibitors are described which are combined with suitable intranasal carriers having a buffer, surfactant and absorption enhancers, in order to achieve a peak plasma concentration of the inhibitor in less than 1 hour, and desirably with in 30 minutes of administration in mammals.
- active ingredient is dispersed in a buffer followed by thickening agent, humectant and surfactant are added.
- the disadvantage associated with this type of suspension formulations is that the dispersed drug particles in the viscous medium may have to over come the resistance caused by the medium to reach onto the surface of the mucous membrane for its dissolution and penetration through the membrane. Further the drug is in solid state with less fluid volume and surface area made available for dissolution and penetration that reduces the absorption of drug compared to solution.
- the dispersion system may delay onset of action initially, though it prolongs the duration of action due to slow penetration. The delay m the onset of action may cause patient incompliance. Further, the limited solubility of the sildenafil citrate may leads to improper dosing of the formulation.
- the above patent also claimed an intranasal powder formulation by using sildenafil mesylate and lactose.
- the composition was milled to an average particles of 20 microns size and filled into a gelatin capsule for use with a commercial nasal device. Inhalation of this powder may cause irritation to the mucous membrane, and absorption of the active ingredient is slow compared to the solution form as described above.
- WO 9966933 a method for rapidly and reliably delivering sildenafil to the systemic circulation of a patient intranasally in a pharmaceutical composition contained sildenafil or a pharmaceutically acceptable salts and carrier was disclosed.
- sildenafil citrate was dissolved with the help of mesylic acid and the pH adjusted to 2.8 to 3.0 with sodium hydroxide.
- a "sildenafil nasal spray solution" containing sildenafil hydrochloride dissolved in phosphate buffer and isotonicity adjusted with sodium chloride.
- aqueous nasal gel which contains sildenafil hydrochloride, methocel and an acetate buffer. It has also disclosed a composite nasal spray solution containing sildenafil hydrochloride, and apomorphine hydrochloride.
- the main objective of the present invention is to provide an improved pharmaceutical composition intended for nasal administration for the treatment of male erectile dysfunction due to organic, pyschogenic and mixed causes containing sildenafil for nasal application.
- Yet another objective of the present invention is to provide an improved pharmaceutical composition in the fo ⁇ of a solution or colloidal dispersion intended for nasal administration for the treatment of male erectile dysfunction due to organic, psychogenic and mixed causes containing sildenafil for nasal application in a suitable pharmaceutical vehicle, comprising of a solvent, co- solvent and / or solubilizing agent, penetration enhancer, stabilising agent, buffering agent, and a tonicity agent; optionally contain an anti-microbial agent and / or viscosity modifying agents.
- Still another objective of the invention is to provide a method for preparing the improved pharmaceutical composition containing sildenafil in the form of a solution or colloidal dispersion intended for nasal administration for the treatment of male erectile dysfunction due to organic, psychogenic and mixed causes.
- the present invention is based on our finding that the poorly water soluble sildenafil or its salt, dissolves completely in mild acids such as lactic acid, hydrochloric acid, ascorbic acid, citric acid, succinic acid, maleic acid, orthophosphoric acid or methyl sulfonic acid and the resulting solution when mixed with solubilisers and penetration enhancers such as polyethyleneglycol, propylene glycol, glycerol, ethyl alcohol, purified diethylene glycol monoethyl ether, propyleneglycol monolaurate and the pH is adjusted 3.0 to 8.0 with citrate, acetate or phosphate buffer and tonicity is adjusted with sodium chloride or dextrose or mannitol, the resulting composition acquires unique property of promoting rapid absorption of sildenafil resulting in rapid onset of action when administered through the nasal route due to synergistic activities of the above said components. It was noticed that the free base of sildenafil is preferably more soluble in as
- lactic acid is more preferable as it is highly biocompatible and is present in organs such as lever, kidney, thymus gland, stratum corneum, human amniotic fluid and other organs and body fluids.
- the above said pharmaceutical composition has rapid onset of action upon administration through nasal route with out any adverse effects due to the synergistic effect of the ingredients employed in the composition which results in keeping the active ingredient namely sildenafil or its salt in solution or dispersion fo ⁇ and absorption is further promoted by penetration enhancers making it absorb readily when the composition is administered through the nasal route for eliciting the desired therapeutic response.
- composition can be filled into a suitable container fitted with nasal applicator.
- the composition can be filled either in multiple dose container fitted with an applicator or "Monospray” (supplied by M/s Valois India Pvt., Ltd., 407, Madhava,Bandra-kurla Complex, Bondra(E), Mumbai- 400 051), filled with single dose of medicament.
- the present invention provides an improved pharmaceutical composition intended for nasal administration for the treatment of male erectile dysfunction due to organic, psychogenic and mixed causes in the form of solution or colloidal dispersion, which comprises solution or colloidal dispersion of Sildenafil or its salt in a "Protogenic" solvent containing solubilisers and penetration enhancers, stabilizing agent, buffering agents and an isotonicity agent, the solution or the dispersion having a pH in the range of 3.0 to 8.0.
- the solution or the dispersion is stable at room temperature and sub ambient temperatures as well without any precipitation and/or re-crystallisation.
- the composition is not a mere admixture of the ingredients employed resulting in a composition having the aggregate properties of the said ingredients.
- the composition in solution form is preferred to the dispersion form as the former has more rapid absorption and onset of action than that of a dispersion form.
- the pharmaceutical composition so formed is then filled in either a multiple dose containers fitted with a mechanical pump and a nasal applicator with an over cap or a "Monospray" (supplied by M/s Valois India Pvt., Ltd., 407, Madhava, Bandra-kurla Complex, Bondra(E), Mumbai- 400 051), nasal liquid unidose device.
- the preferred device is "Monospray”.
- Sildenafil employed in the pharmaceutical composition may be the base or its salt form with organic acids such as citric acid, lactic acid, acetic acid, succinic acid, maleic acid and the like or inorganic acids such as sulphuric acid, hydrochloric acid, orthophosphoric acid etc.
- the amount of sildenafil or its salt employed in the pharmaceutical composition may range from 2.5 to 25.0% w/v, preferably 5.0 to 20.0% w/v more preferably 7.5 to 15.0% w/v.
- the pH of the pharmaceutical composition may preferably be in the range of 3.5 to 5.0.
- the "Protogenic" solvents, which act as proton donors, used m the pharmaceutical composition may be selected from a group of mild acids such as hydrochloric acid, sulphuric acid, lactic acid, solutions of ascorbic acid, citric acid and amphiprotic solvents such as water or their mixtures.
- the volume of such solvents present in the pharmaceutical composition may range from 10.0 to 80.0%v/v, preferably 20.0 to 60.0% v/v.
- the co-solvents when used in the pharmaceutical composition may be selected from a group of "Amphiprotic" solvents, which act as both proton acceptors and proton donors such as the alcohols e.g. ethyl alcohol, propylene glycol, glycerol and polyethylene glycols having a nominal molecular weight of 200 - 600 or N- methyl-2-pyrrolidone, which enhances the solubility of sildenafil or its salts by formation of complex.
- the volume of such co-solvents present in the pharmaceutical composition may range from 1.0 to 50.0% v/v preferably 15.0 to 30.0% v/v.
- the solubilising agents used in the pharmaceutical composition may be selected from purified diethylene glycol monoethyl ether, cyclodextrins, glycerol monostearate, lecithin, poloxomer, polyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, stearic acid, citric acid, and ascorbic acid and the like; surface active agents such as polysorbates, sorbiton esters, polyvinyl alcohol, benzal konium chloride, benzithonium chloride, cetrimide, docusate sodium, sodium lauryl sulphate, octoxynol and the like or a combination of these.
- the amount of such solubilising agent present in the pharmaceutical composition may range from 0.01 to 30.0% w/v, preferably 5.0 to 15.0%w/v.
- solubility enhancers used in the composition may be selected from DL- methionine, caffeine, nicotinamide, vanillin, benzyl alcohol, known in art as solubility enhancers when added to the solutions of other substances.
- the buffering agent used in the pharmaceutical composition may be selected from hydrochloric acid, sodium acetate, glacial acetic acid, orthophosphoric acid, potassium dihydrogen orthophosphate and the like.
- the penetration enhancers used in the pharmaceutical composition of the present invention are selected from ethyl alcohol, propylene glycol, N-methyl-2- pyrrolidone, bile salts, cyclodextrins, propyleneglycol monolaurate in combination with purified diethylene glycol monoethyl ether and the like known in the art for intranasal application.
- the amount of such penetration enhancer present in each ml of the composition may range from 0.1 to 30.0%v/v or w/v, preferably 5.0 to 25.0%v/v or w/v.
- the stabilizing agent used in the pharmaceutical composition maybe selecte ⁇ from among those substances known in the art such as sodium metabisulphite, sodium bisulphite, disodium EDTA, ascorbic acid etc.
- the amount of such stabilizing agents present in the composition may range from 0.01 to 0.5% w/v.
- the pharmaceutical composition may optionally contain anti-microbial agent.
- the anti-microbial agent may be selected from benzyl alcohol, benzalkonium chloride, phenyl mercuric acetate, phenylethyl alcohol and the like.
- the amount of such anti-microbial agent may range from 0.001 to 2.0% w/v preferably 0.02 to 0.5%w/v
- the pharmaceutical composition may also optionally contain a viscosity building agent to increase the viscosity of the composition, there by prolongs the contact time of the composition with the nasal mucosa, preventing its rapid drain to the larynx region of throat.
- the viscosity building agent may be selected from hydrocolloids such as hydroxypropyl methylcellulose, poly acrylic acid and the like or water soluble polymers such as carbopol, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and various grades of polyvinylpyrrolidone i.e. K-15, K-30, K-60 and K-90 etc.
- the amount of such viscosity building agent used in the pharmaceutical composition may range from 0.1 to 5.0% /v.
- the “Monospray” is a nasal liquid unidose device useful in administrating high potency molecules enabling less frequent administration and treatment of crisis conditions.
- the device comprises an actuator with over cap, spring, piston, dosage chamber and a ball for closing the dosage chamber from rear end after filling with medicine.
- a “Monospray” with a nominal volume of the dosage chamber in between 50.0 to 150.0 microliters is selected to deliver 2.5 to 37.5mg, preferably 5.0 to 25.0mg, more preferably 7.5 to 15.0 mg of active substance.
- the percentage of the drug dissolved may range from 2.5 to 25.0%w/v preferably from 5.0 to 15.0%w/v more preferably from 7.5 to 15.0% w/v.
- the dose required may constitute one or more number of actuations depending on the dosing device used and the concentration of drug present in the formulation.
- Each ml contains
- Glacial acetic acid 0.057 % v/v
- Phenylethyl alcohol 0.500 % v/v
- Sildenafil citrate is dissolved in lactic acid and pyrogen free water. Phenylethyl alcohol is added as preservative. Sodium acetate and Glacial acetic acid are added to adjust the pH 3.0. Final volume adjusted to 1.0ml with pyrogen free water. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
- Each ml contains
- Sildenafil citrate is dissolved in mixture of N-methyl-2-pyrrolidone, and pyrogen fee water Benzalkonium chloride solution is added, pH is adjusted to 3.5 with Potassium dihydrogen orthophosphate and Phosphoric acid. Final volume is adjusted to 1.0ml with Pyrogen free water. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray" .
- Each ml contains
- Sildenafil citrate is dissolved in a mixture of polyethylene glycol. ethyl alcohol and hydrochloric acid. pH is adjusted to 3.0 with sodium hydroxide. Pyrogen free water is added to make up to one ml. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray" .
- Each ml contains Sildenafil citrate 7.500 % w/v
- Sildenafil citrate is dissolved in a mixture of propylene glycol, ethyl alcohol and hydrochloric acid. pH is adjusted 3.0 with sodium hydroxide. Pyrogen free water is added to make up the volume to one ml. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
- Each ml contains Sildenafil citrate 10.000 % w/v Polyethylene glycol - 300 30.000 % v/v
- Sildenafil citrate is dissolved in a mixture of polyethylene glycol, glycerol, hydrochloric acid. pH is adjusted to 3.2 with sodium hydroxide. Pyrogen free water is added to make up to one ml. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
- Each ml contains Sildenafil citrate 10.000 % w/v
- Phenyl ethyl alcohol 0.500 % v/v
- Sildenafil citrate is dissolved in a mixture of pyrogen free water, purified diethylene glycol monoethyl ether and octoxynol. Disodium EDTA, polyvinylpyrrolidone K-30, Sodium ascorbate and phenyl ethyl alcohol are added to the above solution. pH is adjusted to 4.0 with sodium acetate and glacial acetic acid. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
- Each ml contains
- Sildenafil is dissolved in a mixture of pyrogen free water, purified diethylene glycol monoethyl ether. Ascorbic acid, disodium EDTA, Polyvinylpyrrolidone, benzyl alcohol are added under continuous mixing. pH is adjusted to 4.0 with sodium acetate and glacial acetic acid. Final volume adjusted to one ml with pyrogen free water. The resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
- Each ml contains Sildenafil citrate 10.000 % w/v
- Glacial acetic acid 3.100% w/v
- Phenyl ethyl alcohol 0.500% w/v
- Sildenafil citrate is dissolved in a mixture of pyrogen free water and hydrochloric acid.
- Purified diethylene glycol monoethyle ether, disodium EDTA, polyvinylpyrrolidone (K-l 5), propylene glycol and phenyl ethyl alcohol is added under continuous mixing. pH is adjusted to 4.0 with sodium acetate and glacial acetic acid. Final volume is adjusted to one ml with pyrogen free water.
- the resultant solution is filtered aseptically and filled into containers fitted with a spraying device for nasal application or into a "Monospray".
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00990872A EP1237538A2 (en) | 1999-11-18 | 2000-10-24 | An improved pharmaceutical composition for treating male erectile dysfunction |
CA002391968A CA2391968A1 (en) | 1999-11-18 | 2000-10-24 | An improved pharmaceutical composition for treating male erectile dysfunction |
AU30485/01A AU3048501A (en) | 1999-11-18 | 2000-10-24 | An improved pharmaceutical composition for treating male erectile dysfunction |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1128MA1999 | 1999-11-18 | ||
IN1128/MAS/99 | 1999-11-18 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001035926A2 true WO2001035926A2 (en) | 2001-05-25 |
WO2001035926A3 WO2001035926A3 (en) | 2001-12-27 |
Family
ID=11096782
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2000/000105 WO2001035926A2 (en) | 1999-11-18 | 2000-10-24 | An improved pharmaceutical composition for treating male erectile dysfunction |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1237538A2 (en) |
AU (1) | AU3048501A (en) |
CA (1) | CA2391968A1 (en) |
WO (1) | WO2001035926A2 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005013937A2 (en) * | 2003-07-23 | 2005-02-17 | Elan Pharma International Ltd. | Novel compositions of sildenafil free base |
WO2010070617A1 (en) | 2008-12-19 | 2010-06-24 | Shimoda Biotech (Pty) Ltd | Inclusion complexes of alpha-cyclodextrin and sildenafil salt |
EP2575765A2 (en) * | 2010-06-07 | 2013-04-10 | Novadel Pharma Inc. | Oral spray formulations and methods for administration of sildenafil |
WO2013085904A1 (en) | 2011-12-05 | 2013-06-13 | Novadel Pharma, Inc. | Oral spray formulations and methods for administration of sildenafil |
GB2497933A (en) * | 2011-12-21 | 2013-07-03 | Londonpharma Ltd | PDE-5 inhibitors for transmucosal delivery |
ES2475942A1 (en) * | 2013-01-11 | 2014-07-11 | Farmalider, S.A. | Pharmaceutical composition of sildenafil citrate in the form of an aqueous solution (Machine-translation by Google Translate, not legally binding) |
FR3008618A1 (en) * | 2013-07-19 | 2015-01-23 | Univ Paris Curie | USE OF COMPOUNDS TO RESTORE THE RESPONSE IN THE LIGHT OF CELLS OF THE RETINA |
CN106132204A (en) * | 2014-03-19 | 2016-11-16 | 维格劳斯解决方案有限责任公司 | Sldenafil solution and its preparation and application |
WO2017024029A1 (en) * | 2015-08-03 | 2017-02-09 | Synergistic Therapeutics, Llc | Sexual dysfunction therapeutic gel |
CN108367010A (en) * | 2015-04-03 | 2018-08-03 | 因塞斯发展股份有限公司 | Silaenafil sublingual spraying preparation |
US20190282496A1 (en) * | 2018-03-19 | 2019-09-19 | Bryn Pharma, LLC | Epinephrine spray formulations |
CN114028348A (en) * | 2021-10-09 | 2022-02-11 | 南京长澳医药科技有限公司 | Sildenafil citrate orally disintegrating tablet and preparation method thereof |
EP4157449A4 (en) * | 2020-05-26 | 2024-05-29 | Strategic Drug Solutions Inc | Formulations and methods for treating erectile dysfunction |
Citations (4)
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---|---|---|---|---|
WO1998053819A1 (en) * | 1997-05-29 | 1998-12-03 | Mochida Pharmaceutical Co., Ltd. | Therapeutic agent for erection failure |
EP0967214A1 (en) * | 1998-06-22 | 1999-12-29 | Pfizer Limited | Intranasal formulations for treating sexual disorders |
WO1999066933A1 (en) * | 1998-06-25 | 1999-12-29 | New Millennium Pharmaceutical Research, Inc. | Nasal administration of sildenafil for the treatment of erectile dysfunction |
WO2000007597A1 (en) * | 1998-07-31 | 2000-02-17 | Hexal Ag | Transmucosal therapeutic system for administering sildenafil |
-
2000
- 2000-10-24 CA CA002391968A patent/CA2391968A1/en not_active Abandoned
- 2000-10-24 AU AU30485/01A patent/AU3048501A/en not_active Abandoned
- 2000-10-24 EP EP00990872A patent/EP1237538A2/en not_active Withdrawn
- 2000-10-24 WO PCT/IN2000/000105 patent/WO2001035926A2/en not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998053819A1 (en) * | 1997-05-29 | 1998-12-03 | Mochida Pharmaceutical Co., Ltd. | Therapeutic agent for erection failure |
EP0967214A1 (en) * | 1998-06-22 | 1999-12-29 | Pfizer Limited | Intranasal formulations for treating sexual disorders |
WO1999066933A1 (en) * | 1998-06-25 | 1999-12-29 | New Millennium Pharmaceutical Research, Inc. | Nasal administration of sildenafil for the treatment of erectile dysfunction |
WO2000007597A1 (en) * | 1998-07-31 | 2000-02-17 | Hexal Ag | Transmucosal therapeutic system for administering sildenafil |
Non-Patent Citations (1)
Title |
---|
BEHL CR ET AL.: "Optimization of systemic nasal drug delivery with pharmaceutical excipients" ADVANCED DRUG DELIVERY REVIEWS, vol. 29, no. 1,2, 5 January 1998 (1998-01-05), pages 117-133, XP000996299 Amsterdam * |
Cited By (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005013937A3 (en) * | 2003-07-23 | 2005-06-16 | Elan Pharma Int Ltd | Novel compositions of sildenafil free base |
WO2005013937A2 (en) * | 2003-07-23 | 2005-02-17 | Elan Pharma International Ltd. | Novel compositions of sildenafil free base |
WO2010070617A1 (en) | 2008-12-19 | 2010-06-24 | Shimoda Biotech (Pty) Ltd | Inclusion complexes of alpha-cyclodextrin and sildenafil salt |
EP2575765A4 (en) * | 2010-06-07 | 2014-08-27 | Suda Ltd | Oral spray formulations and methods for administration of sildenafil |
EP2575765A2 (en) * | 2010-06-07 | 2013-04-10 | Novadel Pharma Inc. | Oral spray formulations and methods for administration of sildenafil |
JP2015500285A (en) * | 2011-12-05 | 2015-01-05 | スダ リミテッド | Sildenafil oral spray formulation and method of administration thereof |
RU2611403C1 (en) * | 2011-12-05 | 2017-02-21 | Суда Лимитед | Compositions in the form of a spray for oral administration and methods of the sildenafil administration |
US9186321B2 (en) | 2011-12-05 | 2015-11-17 | Suda Ltd. | Oral spray formulations and methods for administration of sildenafil |
WO2013085904A1 (en) | 2011-12-05 | 2013-06-13 | Novadel Pharma, Inc. | Oral spray formulations and methods for administration of sildenafil |
AU2012347997B2 (en) * | 2011-12-05 | 2017-07-20 | Suda Limited | Oral spray formulations and methods for administration of sildenafil |
GB2497933A (en) * | 2011-12-21 | 2013-07-03 | Londonpharma Ltd | PDE-5 inhibitors for transmucosal delivery |
GB2497933B (en) * | 2011-12-21 | 2014-12-24 | Londonpharma Ltd | Drug delivery technology |
ES2475942A1 (en) * | 2013-01-11 | 2014-07-11 | Farmalider, S.A. | Pharmaceutical composition of sildenafil citrate in the form of an aqueous solution (Machine-translation by Google Translate, not legally binding) |
FR3008618A1 (en) * | 2013-07-19 | 2015-01-23 | Univ Paris Curie | USE OF COMPOUNDS TO RESTORE THE RESPONSE IN THE LIGHT OF CELLS OF THE RETINA |
WO2015008008A3 (en) * | 2013-07-19 | 2015-04-09 | Universite Pierre Et Marie Curie (Paris 6) | Use of compounds for restoring the response of the cells of the retina to light |
US9968609B2 (en) | 2014-03-19 | 2018-05-15 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
EP3119201A4 (en) * | 2014-03-19 | 2017-03-15 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
CN106132204A (en) * | 2014-03-19 | 2016-11-16 | 维格劳斯解决方案有限责任公司 | Sldenafil solution and its preparation and application |
AU2015233006B2 (en) * | 2014-03-19 | 2018-07-19 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
EP3372083A1 (en) * | 2014-03-19 | 2018-09-12 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
US10211534B2 (en) | 2014-03-19 | 2019-02-19 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
CN106132204B (en) * | 2014-03-19 | 2019-08-20 | 维格劳斯解决方案有限责任公司 | Silaenafil solution and its preparation and application |
AU2018250378B2 (en) * | 2014-03-19 | 2020-05-14 | Vigorous Solutions Ltd. | Sildenafil solutions and methods of making and using same |
CN108367010A (en) * | 2015-04-03 | 2018-08-03 | 因塞斯发展股份有限公司 | Silaenafil sublingual spraying preparation |
EP3277283A4 (en) * | 2015-04-03 | 2018-12-12 | Insys Development Company, Inc. | Sildenafil sublingual spray formulations |
WO2017024029A1 (en) * | 2015-08-03 | 2017-02-09 | Synergistic Therapeutics, Llc | Sexual dysfunction therapeutic gel |
US20190282518A1 (en) * | 2018-03-19 | 2019-09-19 | Bryn Pharma, LLC | Epinephrine spray formulations |
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CN114028348B (en) * | 2021-10-09 | 2022-11-08 | 南京长澳医药科技有限公司 | Sildenafil citrate orally disintegrating tablet and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
WO2001035926A3 (en) | 2001-12-27 |
EP1237538A2 (en) | 2002-09-11 |
CA2391968A1 (en) | 2001-05-25 |
AU3048501A (en) | 2001-05-30 |
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