WO1995030409A1 - Topical polymeric drug delivery system - Google Patents
Topical polymeric drug delivery system Download PDFInfo
- Publication number
- WO1995030409A1 WO1995030409A1 PCT/CA1995/000260 CA9500260W WO9530409A1 WO 1995030409 A1 WO1995030409 A1 WO 1995030409A1 CA 9500260 W CA9500260 W CA 9500260W WO 9530409 A1 WO9530409 A1 WO 9530409A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- drug
- topical
- cyclodextrin
- progesterone
- indomethacin
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
Definitions
- the present invention is directed to a topical polymeric delivery system for the administration of certain drugs over an extended period of time via a non-propellant aerosol pump device.
- Sustained release devices for controlled topical delivery of drugs is a highly useful method of supplying medication when it is beneficial to administer medication continuously.
- the idea of aerosol delivery of a thin film for direct spraying on a wound has been described in an article by Fujita et al., "Pharmaceutical Research” 9, (1992). However, the method described involves a CFC containing aerosol propellant.
- certain drugs can be delivered via a propellant-free aerosol as a component of a polymeric system for prolonged administration compared to conventional formulations.
- the compound indomethacin and certain cyclooxygenase II inhibitors such as 3-[3,4- difluorophenyl]-4-[4-(methylsulfonyl)phenyl]-2(5H)-furanone can be topically applied using the delivery system of the invention resulting in prolonged administration compared to conventional dosage forms.
- the system is capable of providing systemic delivery of the medicament without causing the gastric irritation associated with indomethacin, in particular, and NS.AIDs, in general.
- the system is adaptable to any drug which is soluble and stable in hydroalcoholic solutions and comprises a film forming polymer, a plasticizing agent, a crystallization inhibitor/stabilizer, a penetration enhancer, an alcoholic or 5 hydroalcoholic solution and a suitable drug .
- Suitable drugs for use in therapy with the device of the invention include without limitation:
- Protein drugs such as insulin
- Anti-infectives such as antibiotics, including penicillin, 0 tetracycline, chlorotetracycline bacitracin, ny statin, streptomycin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and erythromycin; sulfonamides, including sulfacetamide, sulfamethizole, sulfamethazine, sulfadiazine, sulfamerazine, and 5 sulfisoxazole, cefoxitin; anti-virals including idoxuridine; and other anti-infectives including nitrofurazone and sodium propionate;
- antibiotics including penicillin, 0 tetracycline, chlorotetracycline bacitracin, ny statin, streptomycin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and
- Steroidal anti-inflammatory agents such as hydrocortisone, cortisone, hydrocortisone acetate, dexamethasone, 0 dexamethasone 21 -phosphate, fluocinolone, triamcinolone, medrysone, prednisolone, prednisolone 21 -phosphate and prednisolone acetate;
- Estrogens such as estrone, 17 ⁇ -estradiol, ethinyl estradiol and diethyl stilbesterol; 5.
- Progestational agents such as progesterone, megestrol, melengestrol, chlormadinone, ethisterone, norethynodrel, 19-nor-progesterone, norethindrone, medroxyprogesterone and 17 ⁇ -hydroxy-progesterone; 6.
- Humoral agents such as the prostaglandins, for example,
- Antipyretics analgesics such as aspirin, sodium salicylate, salicylamide and diflunisal;
- Antispasmodics such as atropine, methantheline, papaverine and methscopolamine bromide
- Antihistamines such as diphenhydramine, dimenhydrinate, tripelennamine, pe henazine and chlorophenazine;
- Non steroidal anti-inflammatory agents such as indomethacin and sulindac; and 11. Cyclooxygenase II inhibitors such as those disclosed in U.S.
- Patent No. 5,409,944 issued April 25, 1995 and those disclosed in copending applications 08/147,804 filed
- This system is particularly useful with drugs such as indomethacin which can cause severe upper gastrointestinal irritation and nausea when administered by conventional means.
- the system involves the use of film forming polymers which are soluble and rapidly form a thin film upon application via a hydrocarbon propellant-free system.
- the film formed allows vapor penetration and can be considered breathable.
- the choice of a chloro- fluoro-carbon (CFC) free preparation was essential due to the potentially environmentally damaging characteristics of CFC propellants.
- CFC chloro- fluoro-carbon
- With the use of a hydrocarbon propellant-free system it was also essential that the solvent employed be volatile enough to allow rapid film formation on administration. Alcohols or hydroalcoholic solutions using lower alkanol solvents such as ethanol and isopropanol have been found useful with ethanol being the preferred solvent. Other potential solvent systems may include ethyl acetate.
- the film forming polymer selected was determined in view of the solvent employed.
- polymers which have been found to be useful in the invention include methacrylates, celluloses, siloxanes and copolymers of methacrylates, celluloses and siloxanes.
- Preferred polymers are methacrylates with poly(2-hydroxy ethyl methacrylate) (PHEMA) the most preferred choice. PHEMA was the most preferred because of the quality of the film formed in the system.
- Plasticizing agents are also necessary for the delivery system.
- the plasticizers are used to impart the desired mechanical properties to the film such as flexibility.
- Suitable plasticizing agents include Tween 20 (polyoxyethylene (20) sorbitan monolaurate) and Tweens of higher molecular weight, low molecular weight polyethylene glycols, glycerine or Labrasols (PEG-8-caprylic-capritriglyceride).
- Preferred plasticizers are Tweens with Tween 20 the most preferred.
- the plasticizing agent is generally present in an amount from about 10% - 50% as a percentage of the total solid contents of the film.
- a crystallization inhibitor/stabilizer and/or a penetration enhancer are used to modulate drug delivery.
- Suitable compounds include substituted cyclodextrins such as hydroxylpropyl beta-cyclodextrin (HPBCD), hydroxyethyl beta-cyclodextrin, diethyl beta-cyclodextrin and hydroxyethyl and hydroxypropyl gamma cyclodextrin and transcutol, urea and isoterpenes.
- HPBCD hydroxylpropyl beta-cyclodextrin
- HPBCD Hydroxypropyl beta-cyclodextrin
- a Beckman Ultrasphere 5 ⁇ C-18 (4.6 x 250 mm) column was used at 40°C with a mobile phase of 35% aqueous (3% acetic acid in distilled water) and 65% organic (15% acetonitrile and 85% methanol) phases. Flow rate was 1 ml/min.
- 4-androsten-17 ⁇ -ol-3-one (testosterone) was used as an internal standard. Detection was by UV spectroscopy measuring at 260 nm.
- An indomethacin standard curve was constructed by preparing standards in methanol which ranged from 0.5 to 10 ⁇ g/ml each with 10 ⁇ g/ml of testosterone.
- the limit of detection for indomethacin quantitation by HPLC with UV detection at 260 nm was determined as 0.05 ⁇ g/ml. Determination was linear over the range 0.1 to 100 ⁇ g/ml.
- the uniformity of detection was determined by injecting the same standard ten times and determining the relative standard deviation for the peak areas obtained. The relative standard deviation was less than two.
- PHEMA was dissolved in a Tween/HPBCD/ethanol solution which had been warmed to 50°C. 3-[3,4-Difluorophenyl]-4-[4- (methylsulfonyl)phenyl]-2(5H)-furanone was added to the solution and stirred until fully dissolved. The resulting solution was filled into a Valois airless pump and made up to volume with ethanol. The pump was sealed with a metered valve (200ml, VP36, 20mm CS gasket 3/522,spring 1674).
- the animals were then injected subplantarly with 50 ⁇ l of a 1% carrageenan solution in saline (FMC Corp., Maine) into the paw using an insulin syringe with a 25-gauge needle (i.e., 500 ⁇ g carrageenan per paw). Three hours later, the paw volume was measured and the increases in the paw volume were calculated. A five hour plasma sample was also taken to correlate the plasma levels with % paw edema inhibition. The animals were euthanized by C02 asphyxiation. Paw edema data were compared with the vehicle control group and percent inhibition calculated taking the values in the control group as 100%.
- the topical formulation was given at different doses to the animals and was also compared to an orally administered dose of indomethacin and a commercially available topical gel formulation of indomethacin. Representative results are shown in Table 1.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP95917847A EP0758229A1 (en) | 1994-05-05 | 1995-05-02 | Topical polymeric drug delivery system |
JP7528565A JPH09512562A (en) | 1994-05-05 | 1995-05-02 | Localized polymer drug delivery system |
AU24024/95A AU2402495A (en) | 1994-05-05 | 1995-05-02 | Topical polymeric drug delivery system |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23840994A | 1994-05-05 | 1994-05-05 | |
US238,409 | 1994-05-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995030409A1 true WO1995030409A1 (en) | 1995-11-16 |
Family
ID=22897769
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CA1995/000260 WO1995030409A1 (en) | 1994-05-05 | 1995-05-02 | Topical polymeric drug delivery system |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0758229A1 (en) |
JP (1) | JPH09512562A (en) |
AU (1) | AU2402495A (en) |
CA (1) | CA2188566A1 (en) |
WO (1) | WO1995030409A1 (en) |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2740038A1 (en) * | 1995-10-20 | 1997-04-25 | Lafon Labor | COMPOSITION FOR TRANSDERMAL ADMINISTRATION |
WO2001037890A1 (en) * | 1999-11-23 | 2001-05-31 | Ever Power Holding Inc | A propellant free spray-on skin patch composition for improving wound healing and for drug administration |
WO2001076594A1 (en) * | 2000-04-10 | 2001-10-18 | Unisearch Limited | Antimicrobial coatings |
AU755165B2 (en) * | 1998-10-23 | 2002-12-05 | Aventis Pharma S.A. | Preparations for topical application of substances having antiandrogenic effect |
US6899894B1 (en) | 1998-06-25 | 2005-05-31 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing hormones and crystallization inhibitors |
WO2008045461A2 (en) * | 2006-10-11 | 2008-04-17 | Oregon Health & Science University | Transdermal diethylstilbestrol for treating prostate cancer |
US8481591B2 (en) | 2010-11-01 | 2013-07-09 | Stiefel Research Australia Pty. Ltd. | Polymeric topical compositions |
US8633178B2 (en) | 2011-11-23 | 2014-01-21 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US8933059B2 (en) | 2012-06-18 | 2015-01-13 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
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US9931349B2 (en) | 2016-04-01 | 2018-04-03 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
US10052386B2 (en) | 2012-06-18 | 2018-08-21 | Therapeuticsmd, Inc. | Progesterone formulations |
US10206932B2 (en) | 2014-05-22 | 2019-02-19 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10258630B2 (en) | 2014-10-22 | 2019-04-16 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
US10471148B2 (en) | 2012-06-18 | 2019-11-12 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable PK profile |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
CN117695225A (en) * | 2023-12-26 | 2024-03-15 | 石家庄石牧药业有限公司 | Aureomycin spray and preparation method thereof |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPO379596A0 (en) | 1996-11-22 | 1996-12-19 | Soltec Research Pty Ltd | Percutaneous delivery system |
DE102018201522A1 (en) * | 2018-02-01 | 2019-08-01 | Beiersdorf Ag | Cosmetic product comprising a dispenser and an anhydrous cosmetic preparation |
CN114404664A (en) * | 2022-02-17 | 2022-04-29 | 浙江瑞谷生物科技有限公司 | Bone repair scaffold material with long-acting slow release function and preparation method and application thereof |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2344291A1 (en) * | 1976-03-19 | 1977-10-14 | Minnesota Mining & Mfg | COMPOSITION FOR TOPICAL APPLICATION OF A MEDICINAL PRODUCT |
EP0319964A1 (en) * | 1987-12-08 | 1989-06-14 | Shionogi Seiyaku Kabushiki Kaisha | Film-formation-type antifungal preparation |
EP0408069A2 (en) * | 1989-07-14 | 1991-01-16 | Union Carbide Chemicals And Plastics Company, Inc. | Emulsions comprising aminopolysaccharides |
US4997643A (en) * | 1989-07-12 | 1991-03-05 | Union Carbide Chemicals And Plastics Company Inc. | Polymeric salt delivery systems |
US5158766A (en) * | 1989-04-13 | 1992-10-27 | Ecolab, Inc. | Storage stable aqueous soluble germicidal film forming composition |
EP0521455A2 (en) * | 1991-07-02 | 1993-01-07 | Takeda Chemical Industries, Ltd. | Aerosol composition containing a film-forming hydroxycarboxylic acid polymer |
EP0542356A1 (en) * | 1991-11-15 | 1993-05-19 | Merck Frosst Canada Inc. | (Quinolin-2-ylmethoxy) indole/cyclodextrin complex as leukotrien inhibitor |
US5262087A (en) * | 1991-05-01 | 1993-11-16 | Kose Corporation | Water-in-oil type emulsified composition |
-
1995
- 1995-05-02 JP JP7528565A patent/JPH09512562A/en active Pending
- 1995-05-02 EP EP95917847A patent/EP0758229A1/en not_active Withdrawn
- 1995-05-02 AU AU24024/95A patent/AU2402495A/en not_active Withdrawn
- 1995-05-02 WO PCT/CA1995/000260 patent/WO1995030409A1/en not_active Application Discontinuation
- 1995-05-02 CA CA 2188566 patent/CA2188566A1/en not_active Abandoned
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2344291A1 (en) * | 1976-03-19 | 1977-10-14 | Minnesota Mining & Mfg | COMPOSITION FOR TOPICAL APPLICATION OF A MEDICINAL PRODUCT |
EP0319964A1 (en) * | 1987-12-08 | 1989-06-14 | Shionogi Seiyaku Kabushiki Kaisha | Film-formation-type antifungal preparation |
US5158766A (en) * | 1989-04-13 | 1992-10-27 | Ecolab, Inc. | Storage stable aqueous soluble germicidal film forming composition |
US4997643A (en) * | 1989-07-12 | 1991-03-05 | Union Carbide Chemicals And Plastics Company Inc. | Polymeric salt delivery systems |
EP0408069A2 (en) * | 1989-07-14 | 1991-01-16 | Union Carbide Chemicals And Plastics Company, Inc. | Emulsions comprising aminopolysaccharides |
US5262087A (en) * | 1991-05-01 | 1993-11-16 | Kose Corporation | Water-in-oil type emulsified composition |
EP0521455A2 (en) * | 1991-07-02 | 1993-01-07 | Takeda Chemical Industries, Ltd. | Aerosol composition containing a film-forming hydroxycarboxylic acid polymer |
EP0542356A1 (en) * | 1991-11-15 | 1993-05-19 | Merck Frosst Canada Inc. | (Quinolin-2-ylmethoxy) indole/cyclodextrin complex as leukotrien inhibitor |
Non-Patent Citations (1)
Title |
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LUONGO, SCIARRA, WARD: "IN VIVO METHOD FOR DETERMINING EFFECTIVENESS OF SPRAY-ON BANDAGES CONTAINING ANTI-INFECTIVES", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 63, no. 9, pages 1376 - 1379 * |
Cited By (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2740038A1 (en) * | 1995-10-20 | 1997-04-25 | Lafon Labor | COMPOSITION FOR TRANSDERMAL ADMINISTRATION |
WO1997015295A1 (en) * | 1995-10-20 | 1997-05-01 | Laboratoire L. Lafon | Composition for transdermal delivery |
US6325990B1 (en) | 1995-10-20 | 2001-12-04 | Laboratoire L. Lafon | Film forming composition for spraying on the skin |
US6899894B1 (en) | 1998-06-25 | 2005-05-31 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing hormones and crystallization inhibitors |
AU755165B2 (en) * | 1998-10-23 | 2002-12-05 | Aventis Pharma S.A. | Preparations for topical application of substances having antiandrogenic effect |
WO2001037890A1 (en) * | 1999-11-23 | 2001-05-31 | Ever Power Holding Inc | A propellant free spray-on skin patch composition for improving wound healing and for drug administration |
WO2001076594A1 (en) * | 2000-04-10 | 2001-10-18 | Unisearch Limited | Antimicrobial coatings |
US7625579B2 (en) | 2000-04-10 | 2009-12-01 | Unisearch Limited | Antimicrobial coatings |
WO2008045461A2 (en) * | 2006-10-11 | 2008-04-17 | Oregon Health & Science University | Transdermal diethylstilbestrol for treating prostate cancer |
WO2008045461A3 (en) * | 2006-10-11 | 2008-12-11 | Univ Oregon Health & Science | Transdermal diethylstilbestrol for treating prostate cancer |
US8481591B2 (en) | 2010-11-01 | 2013-07-09 | Stiefel Research Australia Pty. Ltd. | Polymeric topical compositions |
US8841351B2 (en) | 2010-11-01 | 2014-09-23 | Stiefel Research Australia Pty Ltd. | Polymeric topical compositions |
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Also Published As
Publication number | Publication date |
---|---|
AU2402495A (en) | 1995-11-29 |
JPH09512562A (en) | 1997-12-16 |
EP0758229A1 (en) | 1997-02-19 |
CA2188566A1 (en) | 1995-11-16 |
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