AU2004296539B2 - UV-stable, liquid or semi-solid transdermal administration form comprising a photosensitive active ingredient - Google Patents
UV-stable, liquid or semi-solid transdermal administration form comprising a photosensitive active ingredient Download PDFInfo
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/34—Gestagens
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Description
WO 2005/055975 PCT/EP2004/013839 UV-stable, liquid or semisolid transdermal administration form comprising a photosensitive active ingredient (Description) Technical field The invention relates to semisolid and liquid pharmaceutical administration forms for transdermal application containing a pharmaceutical active ingredient which is photosensitive in the UV range and at least one UV light-absorbing excipient (UV absorber).
Among the semisolid and liquid transdermal administration forms, the invention relates in particular to transdermal gels whose gel base is composed of water, alcohol, at least one gel-forming polymer and optionally further ingredients. Such gels are also designated as hydroalcoholic gels.
The UV absorber is present dissolved or dispersed in the gel.
Prior art It is known from the patent and technical literature that a transdermal application of pharmaceutically active substances has various advantages compared to an oral administration of the pharmaceutical, such as, for example, no first-pass metabolization of the active ingredient by circumvention of the gastrointestinal tract, simultaneous release of the active ingredient over a number of hours, caused by the depot function of the skin as a result the maintenance of a constant plasma level.
In the----case of the known transdermal therapeutic 2 systems, up to now essentially two different pharmaceutical forms have been able to gain acceptance.
A large number of therapeutic patches exist which contain the active ingredient dissolved or suspended in a matrix.
In recent years, moreover, semisolid transdermal administration forms, and here especially gels, have established themselves. A significant advantage of this form compared to the transdermal patches consists in the better skin tolerability -of the nonocclusive pharmaceutical form. Further advantages are seen in an individual doseability and in that the user is not visibly stigmatized as a person who is sick or otherwise worthy of treatment.
Various pharmaceutical active ingredients which are suitable for transdermal application nifedipine, nicotine, arylpropionic acid and benzophenone derivatives, gestodene, levonorgestrel, estradiol and other hormones suitable for transdermal application) are photosensitive. Photosensitive substances absorb radiation within the wavelength spectrum of sunlight, especially within the ultraviolet range (UV, 280- 400 nm). By exposure of pharmaceutical preparations containing photosensitive active ingredients to light, photochemical breakdown of the active ingredients and thus, in the extreme case, a loss of action of the preparation can occur. Moreover, the breakdown products can be a cause of phototoxic or photoallergic reactions of the skin. For example, it is known that under the influence of sunlight ketoprofen gels and other arylpropionic acid and benzophenone derivatives result in an increased occurrence of phototoxic and in some cases photoallergic skin reactions, which are to be attributed to photosensitizing properties of this class of substance. In order to prevent such decomposition processes, suitable protective measures must be taken 3 for transdermal preparations containing photosensitive active ingredients.
In the field of transdermal patches, because of the layered construction typically having at least one active ingredient-containing adhesive layer and a plastic film at the back (backing layer), there is the possibility of accommodating the UV absorber spatially separate from the active ingredient. Inventive solutions for this situation are proposed, for example, in EP 1449526. In the case of patches constructed in layers, there is in particular the possibility of providing the UV absorber in a layer which is spatially in front of the active ingredient-containing layer, in the sense that the harmful light rays must first pass through the UV absorber layer before they reach the active ingredient-containing layer. The active ingredient can thus be protected particularly well from UV light.
This principle, however, is not transferable to other transdermal pharmaceutical forms such as solutions and semisolid preparations, since such unequivocal possibilities of spatial separation of active ingredient and UV absorber within the administration form are not afforded there.
In the case of the transdermal gels known up to now, protection against light only gets attention inasmuch as the preparations are manufactured in lightimpermeable packs, usually aluminized sealed-edge pouches/sachets. This method of protection of semisolid TTS from light during storage can, however, be inadequate on its own. It presupposes that the photosensitive active ingredient is no longer exposed to sunlight after application of the preparation to the skin. Protection from sunlight can take place, for example, by the wearing of clothing over the -4application site. However, this represents for the user, in combination with less clothing, an undesired restriction of the application sites on the body, in particular in climatically warm areas or during climatically warm periods of the year.
It is known that the UV portion of sunlight penetrates into the skin. Thus, UVB light (280-320) penetrates the entire epidermis down to the basal layer. The longerwave UVA light (320-400 nm) penetrates down to the connective tissue. Transdermal gels, as a rule, are applied to a very large area (100-200 cm 2 and more), and the complete active ingredient transport from the outermost layer of the skin (stratum corneum) down to the systemic circulation takes up to 24 hours. The stratum corneum especially as a main penetration barrier functions as an active ingredient reservoir, which stores large parts of the pharmaceutical for a number of hours. The complete spectrum of UV light can penetrate into this area and thus cause photochemical decomposition reactions.
From these points of view, the problem of light sensitivity during application in the case of transdermal gels is even greater than in the case of transdermal patches. In the case of the latter, the exposed application surface is as a rule much smaller and furthermore at least one backing layer of a plastic film lying outside is provided, which as a rule always offers a minimal UV protection.
Semisolid TTS (gels) containing pharmaceutical, also photosensitive, active ingredients are known from the patent literature.
WO-Al-03/082960 describes the preparation of a gel which can contain pharmaceutical active ingredients. In WO-Al-01/60399, a diclofenac-containing gel is demonstrated and the patent specification WO-A2- P \WPDOCS\CRN\XJ\SpccI2679011 spccdl- 19/08f2008 00 5 02/051421 describes a gel composition having at least one androgenic steroid for the treatment and/or prophylaxis of hypogonadism. All the patent specifications make no reference to the sensitive problem of the photosensitivity c 5 and of the protection from light in the case of semisolid IO transdermal administration forms.
0 Description of the invention It is therefore the object of the invention to make available a semisolid transdermal administration form containing a photosensitive pharmaceutical active ingredient, where the application system realizes a high stability without the disadvantages known when using the conventional semisolid transdermal application forms.
At the same time, the harmful concomitant effects, such as, for example, absorption of lightscreen substances into the body possibly resulting from the intentional light protection for the user, should be kept as low as possible.
A first aspect of the invention provides a semisolid or liquid transdermal administration form as a hydroalcoholic gel, comprising a combination of a gestagen and an estrogen, wherein at least one of the gestagen or the estrogen is UV photosensitive; at least one UV absorber without pharmacological activity and a molar mass of greater than 250 gmol-l,wherein the at least one UV absorber is dissolved or dispersed in the administration form, and wherein the partition coefficient [log P] of the at least one UV absorber is greater than 5.0 or less than 0.0.
P \WPDOCS\CRN\JXJISpc\I1267901 I spc doc.-19/8r2008 00 S- 5A SAccording to the invention, the object is achieved by a semisolid or liquid administration form containing a UV photosensitive pharmaceutical active ingredient and at least one UV absorber without pharmacological activity in the 5 concentrations employed, this being present dissolved or ND dispersed in the administration form.
SAccording to the invention, the semisolid administration eC form can be a hydroalcoholic gel. Application forms such as creams, solutions and suspensions also prove to be advantageous.
Surprisingly, with a suitable selection of the UV absorber, a spatial separation between pharmaceutical 6 active ingredient and UV absorber can be achieved under the application conditions: While the transdermal active ingredient necessarily belongs to the group of readily skin-permeating pharmaceutical active ingredients, the UV absorber is selected according to the invention from the group of substances penetrating or permeating the skin as little as possible. Since in the pharmaceutical forms according to the invention transdermal gel or transdermal solution are initially present mixed with one another in the starting state of the active ingredient and the absorber, on diffusion into and through the skin a spatial separation of both components occurs. The poorly penetrating UV absorber remains in the outer skin layers and thus lies spatially between the deeper-penetrating active ingredient and the UV radiation acting from outside the body.
For the selection of a suitable UV absorber, according to the invention the logarithm of the partition coefficient between l-octanol and water (log P designated log P below) and the molecular weight are used.
The partition coefficient(s) [log P] of the UV absorber(s) is/are preferably greater than 3.0 or less than 1.0, particularly preferably greater than 5.0 or less than 0.0. Thus, UV absorbers are preferred which can penetrate or permeate the skin only to a small extent, since they are either too lipophilic or too hydrophilic.
The molar mass of the UV absorber(s) is preferably greater than 250 gmol 1 be.
UV absorber(s) having a molar mass of greater than 500 g/mol is/are particularly preferred. UV absorbers 7 having a molecular weight above 500 g/mol only have a low penetration and permeation power for the skin.
In the transdermal administration form according to the invention, the UV absorber(s) can be present in a proportion of 1-10%, preferably If the semisolid administration form according to the invention contains readily volatile constituents such as, for example, ethanol, methanol, isopropanol or DMSO, the quantitative proportion relates to the sum of the non-readily volatile vehicle constituents or, expressed otherwise, to the formulation remaining on the skin after the escape of all volatile constituents.
It was possible to establish UV-absorbing substance(s) whose absorption maximum lies within the waveband which is responsible for the photochemical decomposition of the active ingredient to be protected.
If protection over a broader UV spectral range or absorption maxima of the active ingredient lying therein is necessary, it proves advantageous to combine two UV-absorbing substances having different absorption maxima.
Furthermore, in the semisolid administration forms according to the invention the substance(s) absorbing in the UV range can be selected from the group which comprises p-aminobenzoic acid and aminobenzoic acid derivatives, preferably 2-ethylhexyl 4-dimethylaminobenzoate, and also cinnamic acid and its derivatives, preferably isoamyl 4-methoxycinnamate, and 3benzylidenebornan-2-one and benzylidenebornan-2-one derivatives, preferably 3-(4')methylbenzylidenebornan- 2-one, 3-(4-sulfo)benzylidenebornan-2-one, and also salicylic acid derivatives, preferably 4-isopropylbenzyl salicylate, 2-ethylhexyl salicylate, 3,3,5trimethylcyclohexyl salicylate, and also 3-imidazol-4- 8 yl-acrylic acid and its esters, 2acid, methylenebisbenzotriazolyltetramethyl-butylphenol, 2cyano-3,3-diphenylacrylic acid, butylmethoxydibenzoylmethane, and also benzophenones or benzophenone derivatives, preferably benzophenone-3, benzophenone-4.
Within the meaning of the present invention, the following substances absorbing in the UV range, in this case chiefly in the UVA range, have proven to be particularly suitable: polyethoxyethyl 4-bis(polyethoxyl)aminobenzoate, 2,2'dihydroxy-4,4'-dimethoxybenzophenone sulfonate, 2-ethylhexyl 4-methoxycinnamate, 3-(4'-trimethylammonium)benzylidenebornan-2-one methylsulfate, 2,4,6-trianiline-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5triazine, dioctyl butamido triazine, bisethylhexyloxyphenol methoxyphenyltriazine, terephthaloylidenedicamphorsulfonic acid, polymer of N-[2 (and 4)-(2-oxoborn-3-ylidenemethyl)benzyl] acrylamide, drometriazole trisiloxane and 2,2'-(1,4-phenylene)bis(lH-benzimidazole-4,6-disulfonic acid, monosodium salt). The trade names of particularly preferred UV absorbers for the UVA range are Tinuvin 326 and Tinosorb S and also Mexoryl XL.
In the case of substances which have an acidic chemical reaction such as carboxylic acids or sulfonic acids, their pharmaceutically acceptable salts such as, preferably and without claim to completeness, K, Na and triethanolamine TEA) salts can also be used.
Further, the administration form according to the invention can contain at least one hormone as a pharmaceutical active ingredient.
9 Furthermore, in the semisolid TTS according to the invention, the pharmaceutical active ingredient(s) can be gestagen(s), preferably gestodene or levonorgestrel or estrogen(s), preferably ethinylestradiol or a combination of estrogen and gestagen, preferably gestodene and ethinylestradiol, and furthermore androgens, preferably testosterone, methyltestosterone or methylnortestosterone (MENT) and also 7a-methyl-ll3fluoro-19-nortestosterone (eF-MENT).
The gel-forming agents of the semisolid administration form are preferably selected from the group which comprises celluloses, preferably hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, Na carboxymethylcellulose, chitosan-EDTA, highly disperse silica, precipitated silica, bentonite, starches, preferably cornstarch, rice starch, potato starch, wheat starch, carboxymethylamylopectin Na, tragacanth, alginates, polyacrylates, polymethacrylates, polyacrylate-polyalkylacrylate crosspolymer, acryloyldimethyl taurate/vinylpyrrolidone copolymer, poly-vinyl alcohol, polyvinylpyrrolidone.
The invention is explained in more detail by the following examples.
Example 1 Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID), which is used in the form of gels for the treatment of swellings and inflammation of the soft parts near joints tendons, tendon sheaths, ligaments and joint capsules), in particular in the shoulder and elbow regions, sports and accidental injuries such as contusions, sprains and strains. Under the influence of sunlight, the occurrence of phototoxic and photoallergic skin reactions is described for such 10 gels. The active ingredient ketoprofen is protected from the light-induced decomposition by the addition of the UV absorber Uvinul DS 49.
Ketoprofen Carbopol 940 1% Uvinul DS 49 2% (2,2'-dihydroxy-4,4'-dimethoxybenzophenone-5,5'disodium sulfonate) Triethanolamine (TEA) 1% Isopropanol Propylene glycol EDTA 0.1% Water to 100% Uvinul DS 49 has a molecular weight of about 478.4 g/mol and an arithmetical log P value of -1.9.
The gel base is prepared from Carbopol, TEA and water according to the generally known pharmaceutical procedures. Uvinul DS 49 and EDTA is then incorporated into this base. Isopropanol, propylene glycol and ketoprofen are blended and subsequently incorporated into the gel base.
Example 2 Gestodene-containing preparations can be used for hormone replacement therapy. Under UV light, decomposition of the active ingredient and a loss of action accompanying it can occur.
Gestodene 1% Uvinul MC 80 2% (2-ethylhexyl 4-methoxycinnamate) Diethylene glycol monoethyl ether Isopropyl myristate Ethanol Hydroxypropylcellulose Water to 100% Uvinul MC 80 has a molecular weight of about 290 g/mol 11 and an arithmetical log P value of 5.37.
Gestodene and Uvinul MC 80 are dissolved in ethanol.
Subsequently, diethylene glycol monoethyl ether, isopropyl myristate and water are added and well blended. The gel is then formed by incorporation of hydroxypropylcellulose in portions and allowed to swell adequately according to the pharmaceutical procedures.
Example 3 Ethinylestradiol-containing preparations can be used for hormone replacement therapy. Under the influence of UV light, decomposition of ethinylestradiol and a loss of action accompanying it can occur.
Ethinylestradiol 0.2% Tinosorb S 2% (bisethylhexyloxyphenyl methoxyphenyltriazine) Diethylene glycol monoethyl ether Isopropyl myristate Ethanol Hydroxypropylcellulose Water to 100% Tinosorb S has a molecular weight of 627.80 g/mol and a partition coefficient log P of 9.
Ethinylestradiol and Tinosorb S are dissolved in ethanol. Subsequently, diethylene glycol monoethyl ether, isopropyl myristate and water are added and well blended. The gel is then formed by incorporation of hydroxypropylcellulose in portions and allowed to swell adequately according to the pharmaceutical procedures.
Example 4 A combination of the hormones ethinylestradiol and gestodene can be used for contraception. Under the influence of UV light, breakdown of the active ingredients and thus a loss of action can occur.
12 Ethinylestradiol 0.4% Gestodene 1% Tinosorb S 2% (bisethylhexyloxyphenyl methoxyphenyltriazine) Diethylene glycol monoethyl ether Propylene glycol Carbopol 940 1% Ethanol Triethanolamine (TEA) 1% Ethinylestradiol, gestodene and Tinosorb S are dissolved in the ethanolic phase. The gel base is prepared from Carbopol, TEA and water according to the generally known pharmaceutical procedures. Propylene glycol and diethylene glycol monoethyl ether are blended and subsequently the ethanolic phase is incorporated into the gel.
Example The active ingredient 7a-methyl-ll-fluoro-19-nortestosterone (eF-MENT) can be employed for hormone replacement therapy in hypogonadal men.
Propylene carbonate 10.0% Ethanol 54.0% Purified water -29.0% eF-MENT 0.8% Tinosorb S Acrylate/C10-30 alkylacrylate 0.8% Crosspolymer (Permulen TR-1) Methylcellulose (Tylopur MH 1000) Glycerol 86% Cyclomethicone Isopropyl myristate Tris(hydroxymethyl)aminomethane to pH 5.8 eF-MENT and Tinosorb S were initially dissolved in ethanol 96%. Pemulen TR-1 and HPC (Klucel HF) were 13 00 swollen in this ethanolic solution. Propylene carbonate was added and mixed with stirring. Subsequently, isopropyl myristate was added, and mixing was carried ;out again. The entire mixture was via a funnel into a mixer/homogenizer system and with stirred briefly. It C- was then homogenized using a rotor-stator homogenizer) at 2000-3500 rpm for 1 minute. Glycerol 86%, and the entire amount of the purified water was Sadded (sucked in) as a schlieren-free mixture in a number of substeps, and the gel distinctly swelled c again. It was stirred (about 5 minutes) until a distinct clarification of the gel was visible.
c- Subsequently, cyclomethicone was incorporated into the mixture with stirring. Subsequently, a 10% strength aqueous tromethamine solution was added with stirring in 3 Substeps for neutralization. At the end of the incorporation, the mixture was homogenized again for 2 minutes at 2700 rpm.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers or steps but not the exclusion of any other integer or group of integers or steps.
The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
Claims (11)
- 2. The semisolid or liquid transdermal administration form as claimed in claim 1, wherein the at least one UV absorber has a molar mass of greater than 500 gmol 1
- 3. The semisolid or liquid transdermal administration form as claimed in claim 1 or claim 2, wherein the gestagen is gestodene and the estrogen is ethinylestradiol.
- 4. The semisolid or liquid transdermal administration form as claimed in claim 1 or claim 2, wherein the gestagen is levonorgestrel.
- 5. The semisolid or liquid transdermal administration form as claimed in any one of claims 1, 2 or 4, wherein the estrogen is ethinylestradiol.
- 6. The semisolid or liquid transdermal administration form as claimed in any one of claims 1 to 5, wherein the at least one UV absorber is present in a proportion of 1-10% based on the sum of the mass of the non-readily volatile vehicle P:\WPDOCS\CRN\ XJ\Spec\I 2679011 I laims doc-20/0&2008 00 0 15 (N constituents. (c 7. The semisolid or liquid transdermal administration form as claimed in any one of claims 1 to 6, wherein the at least one UV absorber is present in a proportion of 2.5% based on Sthe sum of the mass of the non-readily volatile vehicle constituents.
- 8. The semisolid or liquid transdermal administration form as claimed in any one of claims 1 to 7, wherein the at least one UV absorber is selected from the group consisting of: p- aminobenzoic acid and aminobenzoic acid derivatives; 3- benzylidenebornan-2-one and benzylidenebornan-2-one derivatives; a polymer of N-[2(and 4)-(2-oxoborn-3- ylidenemethyl)benzyl]acrylamide and salicylic acid derivatives.
- 9. The semisolid or liquid transdermal administration form as claimed in claim 8, wherein the 3-benzylidenebornan-2-one and benzylidenebornan-2-one derivatives is/are 3- (4')methylbenzylidenebornan-2-one, 3-(4- sulfo)benzylidenebornan-2-one or trimethylammonium)benzylidenebornan-2-one methylsulfate.
- 10. The semisolid or liquid transdermal administration form as claimed in any one of claims 1 to 9, wherein the at least one UV absorber essentially absorbs in the UVA range and is selected from the group consisting of: 2,4,6-trianiline-p- [carbo-2'-ethylhexyl-l'-oxy)-1,3,5-triazine; dioctyl butamido triazine; bisethylhexyloxyphenol; methoxyphenyltriazine; 3-imidazol-4-ylacrylic acid; 2- acid and the K, Na and P.\WPDOCS\ RN\JXJ'Spm 267901 I cldns dx5/09t2O 00 00 16 triethanolamine TEA) salts of sulfonic acid; 2,2'-(1,4-phenylene)bis(lH-benzimidazole-4,6- 00 0 disulfonic acid, monosodium salt); methylenebisbenzotriazolyltetramethylbutylphenol; S 5 drometriazole trisiloxane; 2-cyano-3,3-diphenylacrylic acid; IO terephthaloylidenedicamphorsulfonic acid; (Cq butylmethoxydibenzoylmethane; and benzophenones or Sbenzophenone derivatives.
- 11. The semisolid or liquid transdermal administration form as claimed in claim 10, wherein the benzophenones or benzophenone derivatives are benzophenone-3; benzophenone-4; or 2,2'-dihydroxy-4,4'-dimethoxybenzophenone-5,5'-disodium sulfonate.
- 12. The semisolid or liquid transdermal administration form as claimed in any one of claims 1 to 11, wherein the semisolid or liquid transdermal administration form is colorless and transparent.
- 13. A semisolid or liquid transdermal administration form as a hydroalcoholic gel according to claim 1, substantially as hereinbefore described with reference to the Examples.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03028353.5 | 2003-12-10 | ||
EP03028353A EP1541136A1 (en) | 2003-12-10 | 2003-12-10 | UV light-stable semi-solid transdermal systems comprising a photosensitive active agent and an UV-absorbing component |
PCT/EP2004/013839 WO2005055975A2 (en) | 2003-12-10 | 2004-12-06 | Uv-stable semi-solid transdermal systems comprising a photosensitive active ingredient and a uv absorber |
Publications (2)
Publication Number | Publication Date |
---|---|
AU2004296539A1 AU2004296539A1 (en) | 2005-06-23 |
AU2004296539B2 true AU2004296539B2 (en) | 2008-10-09 |
Family
ID=34486168
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2004296539A Ceased AU2004296539B2 (en) | 2003-12-10 | 2004-12-06 | UV-stable, liquid or semi-solid transdermal administration form comprising a photosensitive active ingredient |
Country Status (24)
Country | Link |
---|---|
EP (2) | EP1541136A1 (en) |
JP (1) | JP2007534643A (en) |
KR (1) | KR20060096512A (en) |
CN (1) | CN101415402A (en) |
AR (1) | AR047140A1 (en) |
AU (1) | AU2004296539B2 (en) |
BR (1) | BRPI0416979A (en) |
CA (1) | CA2548739C (en) |
CR (1) | CR8461A (en) |
EA (1) | EA010239B1 (en) |
EC (1) | ECSP066689A (en) |
GT (1) | GT200400261A (en) |
HN (1) | HN2004000525A (en) |
IL (1) | IL176208A0 (en) |
MX (1) | MXPA06006534A (en) |
MY (1) | MY141728A (en) |
NO (1) | NO20063208L (en) |
NZ (1) | NZ547733A (en) |
PE (1) | PE20050863A1 (en) |
SV (1) | SV2006001971A (en) |
TW (1) | TW200528136A (en) |
UA (1) | UA85861C2 (en) |
WO (1) | WO2005055975A2 (en) |
ZA (1) | ZA200605632B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI395806B (en) | 2010-04-14 | 2013-05-11 | Ind Tech Res Inst | Encapsulation material |
LT2613772T (en) * | 2010-09-06 | 2017-03-27 | Bayer Intellectual Property Gmbh | Low-dose transdermal patches with high drug release |
US10293023B2 (en) | 2013-03-15 | 2019-05-21 | Children's Medical Center Corporation | Method of altering vascular permeability and uses thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60155111A (en) * | 1983-10-20 | 1985-08-15 | Hisamitsu Pharmaceut Co Inc | Stable pharmaceutical for external use containing "ketoprofen(r)" |
FR2804024A1 (en) * | 2000-01-21 | 2001-07-27 | Menarini France | Composition for topical treatment of local inflammation or joint pain, containing non-steroidal antiinflammatory agent and ultraviolet filter to prevent formation of harmful photolysis products |
US6299900B1 (en) * | 1996-02-19 | 2001-10-09 | Monash University | Dermal penetration enhancers and drug delivery systems involving same |
WO2002034200A2 (en) * | 2000-10-27 | 2002-05-02 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic systems comprising photosensitive active substances |
WO2003061707A1 (en) * | 2002-01-22 | 2003-07-31 | Ellipse Pharmaceuticals | Dermatological water-resistant compositions with sun screens and method for production and use of such compositions |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2981523B2 (en) * | 1990-11-19 | 1999-11-22 | 株式会社林原生物化学研究所 | External preparation for skin |
BR9811963A (en) * | 1997-08-21 | 2002-02-05 | Johson & Johnson Consumer Comp | Use of 17-alpha-estradiol for the treatment of aged or sun-damaged skin and / or skin atrophy |
JP2000292428A (en) * | 1999-04-05 | 2000-10-20 | Umeda Jimusho:Kk | New measurement method and device of internal secretion disturbance activity of environmental chemical substance |
JP2001129566A (en) * | 1999-11-05 | 2001-05-15 | Mitsubishi Heavy Ind Ltd | Method and apparatus for treating harmful substance |
ITFI20020144A1 (en) * | 2002-08-01 | 2004-02-02 | Menarini Farma Ind | STABILIZED TOPICAL FORMULATIONS CONTAINING KETOPROFENE. |
-
2003
- 2003-12-10 EP EP03028353A patent/EP1541136A1/en not_active Withdrawn
-
2004
- 2004-06-12 UA UAA200607539A patent/UA85861C2/en unknown
- 2004-12-02 TW TW93137245A patent/TW200528136A/en unknown
- 2004-12-06 EA EA200601084A patent/EA010239B1/en not_active IP Right Cessation
- 2004-12-06 CN CNA2004800369947A patent/CN101415402A/en active Pending
- 2004-12-06 JP JP2006543451A patent/JP2007534643A/en active Pending
- 2004-12-06 NZ NZ547733A patent/NZ547733A/en unknown
- 2004-12-06 CA CA002548739A patent/CA2548739C/en not_active Expired - Fee Related
- 2004-12-06 EP EP04803546A patent/EP1703892A2/en not_active Withdrawn
- 2004-12-06 BR BRPI0416979-4A patent/BRPI0416979A/en not_active IP Right Cessation
- 2004-12-06 AU AU2004296539A patent/AU2004296539B2/en not_active Ceased
- 2004-12-06 WO PCT/EP2004/013839 patent/WO2005055975A2/en active Application Filing
- 2004-12-06 KR KR1020067013775A patent/KR20060096512A/en not_active Application Discontinuation
- 2004-12-10 SV SV2004001971A patent/SV2006001971A/en not_active Application Discontinuation
- 2004-12-10 PE PE2004001228A patent/PE20050863A1/en not_active Application Discontinuation
- 2004-12-10 GT GT200400261A patent/GT200400261A/en unknown
- 2004-12-10 HN HN2004000525A patent/HN2004000525A/en unknown
- 2004-12-10 MY MYPI20045109A patent/MY141728A/en unknown
- 2004-12-10 AR ARP040104604A patent/AR047140A1/en unknown
-
2006
- 2006-06-08 IL IL176208A patent/IL176208A0/en unknown
- 2006-06-08 MX MXPA06006534 patent/MXPA06006534A/en unknown
- 2006-06-16 CR CR8461A patent/CR8461A/en not_active Application Discontinuation
- 2006-07-07 ZA ZA200605632A patent/ZA200605632B/en unknown
- 2006-07-07 EC EC2006006689A patent/ECSP066689A/en unknown
- 2006-07-10 NO NO20063208A patent/NO20063208L/en not_active Application Discontinuation
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60155111A (en) * | 1983-10-20 | 1985-08-15 | Hisamitsu Pharmaceut Co Inc | Stable pharmaceutical for external use containing "ketoprofen(r)" |
US6299900B1 (en) * | 1996-02-19 | 2001-10-09 | Monash University | Dermal penetration enhancers and drug delivery systems involving same |
FR2804024A1 (en) * | 2000-01-21 | 2001-07-27 | Menarini France | Composition for topical treatment of local inflammation or joint pain, containing non-steroidal antiinflammatory agent and ultraviolet filter to prevent formation of harmful photolysis products |
WO2002034200A2 (en) * | 2000-10-27 | 2002-05-02 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic systems comprising photosensitive active substances |
WO2003061707A1 (en) * | 2002-01-22 | 2003-07-31 | Ellipse Pharmaceuticals | Dermatological water-resistant compositions with sun screens and method for production and use of such compositions |
Non-Patent Citations (1)
Title |
---|
Derwent Publication, AN 1985-239345, XP002277495 & JP 60155111 A * |
Also Published As
Publication number | Publication date |
---|---|
UA85861C2 (en) | 2009-03-10 |
SV2006001971A (en) | 2006-02-15 |
EP1541136A1 (en) | 2005-06-15 |
JP2007534643A (en) | 2007-11-29 |
MXPA06006534A (en) | 2006-08-01 |
HN2004000525A (en) | 2010-09-17 |
EA200601084A1 (en) | 2006-12-29 |
GT200400261A (en) | 2005-10-31 |
CR8461A (en) | 2006-12-07 |
WO2005055975A3 (en) | 2009-03-12 |
CA2548739A1 (en) | 2005-06-23 |
TW200528136A (en) | 2005-09-01 |
BRPI0416979A (en) | 2007-02-21 |
CN101415402A (en) | 2009-04-22 |
ZA200605632B (en) | 2008-06-25 |
NZ547733A (en) | 2010-02-26 |
EP1703892A2 (en) | 2006-09-27 |
AR047140A1 (en) | 2006-01-11 |
EA010239B1 (en) | 2008-06-30 |
AU2004296539A1 (en) | 2005-06-23 |
PE20050863A1 (en) | 2005-11-02 |
KR20060096512A (en) | 2006-09-11 |
MY141728A (en) | 2010-06-15 |
IL176208A0 (en) | 2006-10-05 |
CA2548739C (en) | 2009-08-18 |
WO2005055975A2 (en) | 2005-06-23 |
NO20063208L (en) | 2006-07-10 |
ECSP066689A (en) | 2006-10-31 |
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Legal Events
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FGA | Letters patent sealed or granted (standard patent) | ||
MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |