CA1229554A - Meclofenamic acid topical pharmaceutical composition - Google Patents
Meclofenamic acid topical pharmaceutical compositionInfo
- Publication number
- CA1229554A CA1229554A CA000448165A CA448165A CA1229554A CA 1229554 A CA1229554 A CA 1229554A CA 000448165 A CA000448165 A CA 000448165A CA 448165 A CA448165 A CA 448165A CA 1229554 A CA1229554 A CA 1229554A
- Authority
- CA
- Canada
- Prior art keywords
- polyethylene glycol
- weight percent
- meclofenamic acid
- composition according
- triglyceride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- 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
- A61K47/06—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
-
- 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
- A61K47/06—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
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT
A clear gel and a cream pharmaceutical composition containing meclofenamic acid are disclosed. The clear gel composition is prepared by dissolving meclofenamic acid in polyethylene glycol monolaurate and polyekhylene glycol lanolin oil and adding isopropyl alcohol with mixing and finally adding colloidal silicon dioxide with mixing. The cream composition is prepared by adding meclofenamic acid or the sodium salt thereof to an emulsion prepared by mixing a warm aqueous solution of sorbic acid with a melt of poly-ethylene glycol monostearate, glyceryl monostearate, caprylic and capric triglyceride and mineral oil.
The resulting compositions are indicated for the treatment of inflammation.
A clear gel and a cream pharmaceutical composition containing meclofenamic acid are disclosed. The clear gel composition is prepared by dissolving meclofenamic acid in polyethylene glycol monolaurate and polyekhylene glycol lanolin oil and adding isopropyl alcohol with mixing and finally adding colloidal silicon dioxide with mixing. The cream composition is prepared by adding meclofenamic acid or the sodium salt thereof to an emulsion prepared by mixing a warm aqueous solution of sorbic acid with a melt of poly-ethylene glycol monostearate, glyceryl monostearate, caprylic and capric triglyceride and mineral oil.
The resulting compositions are indicated for the treatment of inflammation.
Description
I
The present invention relates to topically active compositions containing meclofenamic acid in a suitable topical vehicle. Also encompassed within the scope of this invention is the process for production of said topically active compositions and the treatment of inflammation by topical application of said compositions.
Although not completely understood, the effects of non-asteroidal anti-inflammatory drugs (SAID) is thought to be due to their interference with prostaglandin biosynthesis.
This activity is likely to be related to the inhibition of cyclooxygenase and lipoxygenase in arachidonic acid metabolism.
Side effects, mostly associated with gastrointestinal disturbances, have been reported with oral UNSAID therapy.
topical application should be considered a valuable alternative mode of administration. Direct application to inflamed joints should result in appreciably lower systemic blood levels and hence better tolerance.
The non-steroidal anti-inflammatory drug, meclofenamic acid, its production and its use in the treatment of arthritis by oral administration is described in United States Patent Jo. 3,313,848 issued April 11, 19~7.
P. Chanterelle et at, Arzneim-Forsch, Drug Ryes., 32 (1) and United States Patent No. 4,185,iOO describe the use of combinations containing topically active antiinflammatory corticosteroid and non-steroidal anti-inflammatory agents for the topical treatment of cutaneous disorders.
Ed ~9S5~
Meclofenamic acid is virtually water-insoluble and therefore, a hydroalcoholic gel could not be formulated at the desired concentration ox drug. The drug is also insoluble in glycerin, isopropyl myristate and mineral oil.
The use of the latter two solvents is described in United States Patent 4,185,100. Its volubility in propylene glycol, ethyl alcohol and linoleic acid is somewhat less than I
According to the present invention it was found that meclofenamic acid is soluble in the following water-miscible solvents to an extent of at best 5% at room temperature and more with the aid of heating up to 50C:
polyethylene glycol 400 polyethylene glycol -8 monolaurate polyethylene glycol glucose ethers also referred to as [PEG Glucose Ethers (Glaucoma - E 10, P-20)]
polyethylene glycol - 75 Lanolin Oil also referred to as (Lantrol AWN) polypropylene (PPG)-5-Ceteth-10 Phosphate also referred to a (Crodafos SO) Meclofenamic acid was found to have a highly favorable octanol/water partition coefficient and we have now discovered novel gel and cream formulations which provide maximal topical activity for meclofenamic acid.
issue Broadly speaking the gel formulation is a clear gel of meclofenamic acid in a co-solvent system of a polyethylene glycol ester, water soluble lanolin oil, an alcohol and a thickening agent.
The polyethylene glycol ester is selected from the group of polyethylene glycol esters consisting of polyethylene glycol moo- and dilaurate and polyethylene glycol moo- and dwelt. The preferred polyethylene glycol esters are polyp ethylene glycol -8 monolaurate, polyethylene glycol -8 and -8 lo dilaurate, polyethylene glycol -8 moonlit and polyethylene glycol -8 dwelt. The most preferred polyethylene glycol ester is polyethylene glycol 400 monolaurate.
The preferred water soluble lanolin oil is a polyp ethylene glycol lanolin oil and the most preferred is polyp ethylene glycol - 75 lanolin oil.
The preferred thickening agent is silicon dioxide colloidal.
Finally the alcohol is selected from the group of 3 and 4 carbon containing alcohols consisting of propel, isopropyl, bottle, sec-butyl and tert-butyl. The preferred alcohol is isopropyl alcohol.
The meclofenamic acid is present in the range of about 3 to 10~ by weight and preferably about 5% by weight.
- The polyethylene glycol ester is present in the range of 30 to 60% by weight and preferably about 50% by weight. The water soluble lanolin is present in the range of 0 to 20~ by weight and preferably about 10% by weight. The thickening agent is present from 5 to 10% by weight and preferably about 5% by weight. Sufficient alcohol is used to gas. the ` TV,`
!`' formulation.
955~
The gel formulation is prepared by dissolving meclofenamic acid in a heated and stirred solution of polyethylene glycol ester and water soluble lanolin oil. The solution is allowed to cool and an alcohol is added with continued stirring until the solution cools to room tempera-lure. A thickening agent is added with stirring and finally sufficient alcohol to make a clear gel.
The cream formulation is a homogenized emulsion of a polyethylene glycol ester, glycerol or propylene glycol menstruate, a triglyceride, mineral oil and an aqueous solution of a preservative to which is added meclofenamic acid or the sodium salt thereof.
The polyethylene glycol ester is selected from the group consisting of polyethylene glycol menstruate and polyp ethylene glycol monolaurate. The preferred polyethylene glycol esters are polyethylene glycol 40, 45, 50, 75 and I -6-32 menstruate and polyethylene glycol -75 and -150 monolaurate. The most preferred polyethylene glycol ester is polyethylene glycol -6-32 menstruate.
The triglyceride is selected from the group consisting of caprylic/capric triglyceride, caprylic/capric/stearic triglyceride and hydrogenated palm oil triglyceride. The preferred triglyceride is caprylic/capric triglyceride.
The preservative is selected from the group consisting of sorbic acid and benzoic acid and a combination of methylparaben and propylparaben. The preferred preservative it sorbic acid.
I,," .
US
The meclofenamic acid or the sodium salt thereof is present in the range of about 3 to 10~ by weight preferably about 5% by weight. Meclofenamic acid is the preferred form of the active ingredient.
The polyethylene glycol ester and glycerol or propylene menstruate are present in the range of 5 to 12% by weight and preferably about 9% by weight. The triglyceride is present in the range 3 to 10% by weight and preferably about 5% by weight. The mineral oil is present in the range of 5 to 10~ by weight and preferably about 8% by weight.
The preservative is present in sufficient amount to function as a preservative. Usually about 0.1% by weight is sufficient.
The cream formulation is prepared by adding meclofenamic ; acid or the sodium salt thereof to an emulsion prepared by mixing a warm aqueous solution of preservative with a melt of a polyethylene glycol ester, glycerol or propylene menstruate, a triglyceride and mineral oil.
Toe pi is adjusted to the range 4.5 to 5 and the cream homogenized and cooled to room temperature.
In order to further illustrate the practice of this invention, the following examples are included-A clear gel containing 5% meclofenamic acid was prepared from the following ingredients:
US
% INGREDIENTS 1000.00 g 5.0 1. Meclofenamic acid 50.00 g 50.0 2. PEG-8 Laureate (PEG 400 monolaurate) gas. o'er g 10.0 3. PEG-75 Lanolin Oil gas. o'er g (Lantrol AWN) 5.0 4. Silicon Dioxide Colloidal OF gas. o'er g - 5. Isopropyl Alcohol US gas. to 1000.00 g The PEG-8 laureate (polyethylene glycol 400 monolaurate) and PEG-75 lanolin oil (Lantrol AWN) was heated to 90 C. To the resulting solution was added meclofenamic acid with heating to maintain a temperature of 90C and with stirring until the meclofenamic acid dissolved. The solution was allowed to cool to 40C and 300 g. of isopropyl alcohol was added. Stirring was continued until the solution cooled to room temperature. Silicon dioxide colloidal NO was added to the solution with high shear mixing for 10 minutes.
Sufficient isopropyl alcohol was added to make 1000 g and mixed until a uniform, clear, pale yellow gel containing 5%
meclofenamic acid was obtained.
A gel containing 5% sodium meclofenamate is prepared according to the process of EXAMPLE 1 by replacing the meclofenamic acid with 50.00 g of sodium meclofenamate.
so A cream containing mecloEenamic acid is prepared from the following ingredients:
INGREDIE~TS1000.00 g 5.00 1. Meclofenamic Acid 50.00 g 9.00 2. Polyethylene Glycol -6-3290.00 g Menstruate 9.00 3. Glycerol Menstruate g 5.00 4. Caprylic/Capric Triglyceride 50.00 g 108.00 5. Mineral Oil 80.00 g 0.1 6. Sorbic Acid (preservative g - 7.~Triethanolamine gas. to pi 4.5 - 5.0 - 8. Water, distilled gas. Tao g : The polyethylene glycol -6-32 menstruate, glycerol menstruate, caprylic/capric triglyceride and mineral oil are combined in a suitable jacketed tank and melted by heating to 60 C.
An aqueous solution of sorbic acid is prepared in a jacketed tank equipped with a paddle mixer by dissolving the sorbic acid with mixing in the minimum amount of water preheated to 60C. The aqueous solution of sorbic acid is added with agitation to the melted polyethylene glycol -6-32 menstruate, glycerol menstruate, caprylic/capric trimly-cerise and mineral oil to form an emulsion. The mecloEenamic acid is added to the emulsion with continued agitation and while maintaining the temperature at 60C.
I I. i it The pi of the resulting cream it adjusted to 4.5 - 5.0 with the addition of triethanolamine and -the cream is circulated through an in-line homogenizer and allowed to cool to room temperature.
A cream containing I sodium meclofenamate is prepared according to the procedure of EXAMPLE 3 by replacing the meclofenamic acid with 50.00 g of sodium meclofenamate.
The present invention relates to topically active compositions containing meclofenamic acid in a suitable topical vehicle. Also encompassed within the scope of this invention is the process for production of said topically active compositions and the treatment of inflammation by topical application of said compositions.
Although not completely understood, the effects of non-asteroidal anti-inflammatory drugs (SAID) is thought to be due to their interference with prostaglandin biosynthesis.
This activity is likely to be related to the inhibition of cyclooxygenase and lipoxygenase in arachidonic acid metabolism.
Side effects, mostly associated with gastrointestinal disturbances, have been reported with oral UNSAID therapy.
topical application should be considered a valuable alternative mode of administration. Direct application to inflamed joints should result in appreciably lower systemic blood levels and hence better tolerance.
The non-steroidal anti-inflammatory drug, meclofenamic acid, its production and its use in the treatment of arthritis by oral administration is described in United States Patent Jo. 3,313,848 issued April 11, 19~7.
P. Chanterelle et at, Arzneim-Forsch, Drug Ryes., 32 (1) and United States Patent No. 4,185,iOO describe the use of combinations containing topically active antiinflammatory corticosteroid and non-steroidal anti-inflammatory agents for the topical treatment of cutaneous disorders.
Ed ~9S5~
Meclofenamic acid is virtually water-insoluble and therefore, a hydroalcoholic gel could not be formulated at the desired concentration ox drug. The drug is also insoluble in glycerin, isopropyl myristate and mineral oil.
The use of the latter two solvents is described in United States Patent 4,185,100. Its volubility in propylene glycol, ethyl alcohol and linoleic acid is somewhat less than I
According to the present invention it was found that meclofenamic acid is soluble in the following water-miscible solvents to an extent of at best 5% at room temperature and more with the aid of heating up to 50C:
polyethylene glycol 400 polyethylene glycol -8 monolaurate polyethylene glycol glucose ethers also referred to as [PEG Glucose Ethers (Glaucoma - E 10, P-20)]
polyethylene glycol - 75 Lanolin Oil also referred to as (Lantrol AWN) polypropylene (PPG)-5-Ceteth-10 Phosphate also referred to a (Crodafos SO) Meclofenamic acid was found to have a highly favorable octanol/water partition coefficient and we have now discovered novel gel and cream formulations which provide maximal topical activity for meclofenamic acid.
issue Broadly speaking the gel formulation is a clear gel of meclofenamic acid in a co-solvent system of a polyethylene glycol ester, water soluble lanolin oil, an alcohol and a thickening agent.
The polyethylene glycol ester is selected from the group of polyethylene glycol esters consisting of polyethylene glycol moo- and dilaurate and polyethylene glycol moo- and dwelt. The preferred polyethylene glycol esters are polyp ethylene glycol -8 monolaurate, polyethylene glycol -8 and -8 lo dilaurate, polyethylene glycol -8 moonlit and polyethylene glycol -8 dwelt. The most preferred polyethylene glycol ester is polyethylene glycol 400 monolaurate.
The preferred water soluble lanolin oil is a polyp ethylene glycol lanolin oil and the most preferred is polyp ethylene glycol - 75 lanolin oil.
The preferred thickening agent is silicon dioxide colloidal.
Finally the alcohol is selected from the group of 3 and 4 carbon containing alcohols consisting of propel, isopropyl, bottle, sec-butyl and tert-butyl. The preferred alcohol is isopropyl alcohol.
The meclofenamic acid is present in the range of about 3 to 10~ by weight and preferably about 5% by weight.
- The polyethylene glycol ester is present in the range of 30 to 60% by weight and preferably about 50% by weight. The water soluble lanolin is present in the range of 0 to 20~ by weight and preferably about 10% by weight. The thickening agent is present from 5 to 10% by weight and preferably about 5% by weight. Sufficient alcohol is used to gas. the ` TV,`
!`' formulation.
955~
The gel formulation is prepared by dissolving meclofenamic acid in a heated and stirred solution of polyethylene glycol ester and water soluble lanolin oil. The solution is allowed to cool and an alcohol is added with continued stirring until the solution cools to room tempera-lure. A thickening agent is added with stirring and finally sufficient alcohol to make a clear gel.
The cream formulation is a homogenized emulsion of a polyethylene glycol ester, glycerol or propylene glycol menstruate, a triglyceride, mineral oil and an aqueous solution of a preservative to which is added meclofenamic acid or the sodium salt thereof.
The polyethylene glycol ester is selected from the group consisting of polyethylene glycol menstruate and polyp ethylene glycol monolaurate. The preferred polyethylene glycol esters are polyethylene glycol 40, 45, 50, 75 and I -6-32 menstruate and polyethylene glycol -75 and -150 monolaurate. The most preferred polyethylene glycol ester is polyethylene glycol -6-32 menstruate.
The triglyceride is selected from the group consisting of caprylic/capric triglyceride, caprylic/capric/stearic triglyceride and hydrogenated palm oil triglyceride. The preferred triglyceride is caprylic/capric triglyceride.
The preservative is selected from the group consisting of sorbic acid and benzoic acid and a combination of methylparaben and propylparaben. The preferred preservative it sorbic acid.
I,," .
US
The meclofenamic acid or the sodium salt thereof is present in the range of about 3 to 10~ by weight preferably about 5% by weight. Meclofenamic acid is the preferred form of the active ingredient.
The polyethylene glycol ester and glycerol or propylene menstruate are present in the range of 5 to 12% by weight and preferably about 9% by weight. The triglyceride is present in the range 3 to 10% by weight and preferably about 5% by weight. The mineral oil is present in the range of 5 to 10~ by weight and preferably about 8% by weight.
The preservative is present in sufficient amount to function as a preservative. Usually about 0.1% by weight is sufficient.
The cream formulation is prepared by adding meclofenamic ; acid or the sodium salt thereof to an emulsion prepared by mixing a warm aqueous solution of preservative with a melt of a polyethylene glycol ester, glycerol or propylene menstruate, a triglyceride and mineral oil.
Toe pi is adjusted to the range 4.5 to 5 and the cream homogenized and cooled to room temperature.
In order to further illustrate the practice of this invention, the following examples are included-A clear gel containing 5% meclofenamic acid was prepared from the following ingredients:
US
% INGREDIENTS 1000.00 g 5.0 1. Meclofenamic acid 50.00 g 50.0 2. PEG-8 Laureate (PEG 400 monolaurate) gas. o'er g 10.0 3. PEG-75 Lanolin Oil gas. o'er g (Lantrol AWN) 5.0 4. Silicon Dioxide Colloidal OF gas. o'er g - 5. Isopropyl Alcohol US gas. to 1000.00 g The PEG-8 laureate (polyethylene glycol 400 monolaurate) and PEG-75 lanolin oil (Lantrol AWN) was heated to 90 C. To the resulting solution was added meclofenamic acid with heating to maintain a temperature of 90C and with stirring until the meclofenamic acid dissolved. The solution was allowed to cool to 40C and 300 g. of isopropyl alcohol was added. Stirring was continued until the solution cooled to room temperature. Silicon dioxide colloidal NO was added to the solution with high shear mixing for 10 minutes.
Sufficient isopropyl alcohol was added to make 1000 g and mixed until a uniform, clear, pale yellow gel containing 5%
meclofenamic acid was obtained.
A gel containing 5% sodium meclofenamate is prepared according to the process of EXAMPLE 1 by replacing the meclofenamic acid with 50.00 g of sodium meclofenamate.
so A cream containing mecloEenamic acid is prepared from the following ingredients:
INGREDIE~TS1000.00 g 5.00 1. Meclofenamic Acid 50.00 g 9.00 2. Polyethylene Glycol -6-3290.00 g Menstruate 9.00 3. Glycerol Menstruate g 5.00 4. Caprylic/Capric Triglyceride 50.00 g 108.00 5. Mineral Oil 80.00 g 0.1 6. Sorbic Acid (preservative g - 7.~Triethanolamine gas. to pi 4.5 - 5.0 - 8. Water, distilled gas. Tao g : The polyethylene glycol -6-32 menstruate, glycerol menstruate, caprylic/capric triglyceride and mineral oil are combined in a suitable jacketed tank and melted by heating to 60 C.
An aqueous solution of sorbic acid is prepared in a jacketed tank equipped with a paddle mixer by dissolving the sorbic acid with mixing in the minimum amount of water preheated to 60C. The aqueous solution of sorbic acid is added with agitation to the melted polyethylene glycol -6-32 menstruate, glycerol menstruate, caprylic/capric trimly-cerise and mineral oil to form an emulsion. The mecloEenamic acid is added to the emulsion with continued agitation and while maintaining the temperature at 60C.
I I. i it The pi of the resulting cream it adjusted to 4.5 - 5.0 with the addition of triethanolamine and -the cream is circulated through an in-line homogenizer and allowed to cool to room temperature.
A cream containing I sodium meclofenamate is prepared according to the procedure of EXAMPLE 3 by replacing the meclofenamic acid with 50.00 g of sodium meclofenamate.
Claims (10)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A stable, non-aqueous, clear gell composition, comprising:
from about 3 to about 10 weight percent meclofenamic acid, from about 30 to about 60 weight percent of a polyethylene glycol ester, from zero to about 20 weight percent of a water soluble lanolin oil, from about 5 to about 10 weight percent of a thickening agent and sufficient alcohol to make a clear gel, wherein the alcohol is selected from the group consisting or propyl, isopropyl, butyl, sec-butyl and tert-butyl.
from about 3 to about 10 weight percent meclofenamic acid, from about 30 to about 60 weight percent of a polyethylene glycol ester, from zero to about 20 weight percent of a water soluble lanolin oil, from about 5 to about 10 weight percent of a thickening agent and sufficient alcohol to make a clear gel, wherein the alcohol is selected from the group consisting or propyl, isopropyl, butyl, sec-butyl and tert-butyl.
2. A gel composition according to claim 1, wherein the poly-ethylene glycol ester is selected from the group consisting of polyethlene glycol mono- and dilaurate, and polyethylene glycol mono- and dioleate; the water soluble lanolin oil is a polyethylene glycol lanolin oil; and the thickening agent is colloidal silicon dioxide.
3. A gel composition according to claim 2, wherein the poly-ethylene glycol ester is selected from the group consisting of polyethylene glycol-8 monolaurate, polyethylene glycol-4 and -8 dilaurate, polyethylene glycol-8 monoleate and polyethylene glycol-8 dioleate.
4. A gel composition according to claim 3, comprising:
about 5 weight percent meclofenamic acid, about 50 weight percent polyethylene glycol-8 monolaurate, about 10 weight percent poly-ethylene glycol-75 lanolin oil, about 5 weight percent colloidal silicon dioxide and about 30 weight percent isopropyl alcohol.
about 5 weight percent meclofenamic acid, about 50 weight percent polyethylene glycol-8 monolaurate, about 10 weight percent poly-ethylene glycol-75 lanolin oil, about 5 weight percent colloidal silicon dioxide and about 30 weight percent isopropyl alcohol.
5. A process for producing a gel composition according to claim 1, 2 or 3, comprising:
a) dissolving the meclofenamic acid in a heated and stirred solution of the polyethylene glycol ester and water soluble lanolin oil;
b) adding the alcohol, and cooling to room temperature;
and c) adding the thickening agent with high shear stirring until a clear gel is obtained.
a) dissolving the meclofenamic acid in a heated and stirred solution of the polyethylene glycol ester and water soluble lanolin oil;
b) adding the alcohol, and cooling to room temperature;
and c) adding the thickening agent with high shear stirring until a clear gel is obtained.
6. A cream composition, comprising: from about 3 to about 10 weight percent meclofenamic acid, from about 5 to about 12 weight percent of a polyethylene glycol ester, from about 5 to about 12 weight percent of glyceryl or propylene monostearate, from about 3 to about 10 weight percent of a triglyceride, from about 5 to about 10 weight percent of a mineral oil and about 0.1 weight percent of a preservative.
7. A cream composition according to claim 6, wherein the polyethylene glycol ester is selected from the group consisting of polyethylene glycol monostearate and polyethylene glycol mono-laurate; the triglyceride is selected from the group consisting of caprylic/capric triglyceride, caprylic/capric/stearic triglyceride and hydrogenated palm oil triglyceride; and the preservative is selected from the group consisting of sorbic acid, benzoic acid and a combination of methylparaben and propylparaben.
8. A cream composition according to claim 7, wherein the polyethylene glycol ester is selected from the group consisting of polyethylene glycol-40, -45, -50, -75 and -6-32 monostearate, and polyethylene glycol-75 and -150 monolaurate.
9. A cream composition according to claim 8, comprising:
about 5 weight percent meclofenamic acid, about 9 weight percent polyethylene glycol-6-32 monostearate, about 9 weight percent glyceryl monostearate, about 5 weight percent caprylic/capric triglyceride, about 8 weight percent mineral oil and sorbic acid preservative adjusted to a pH of about 4.5 to 5Ø
about 5 weight percent meclofenamic acid, about 9 weight percent polyethylene glycol-6-32 monostearate, about 9 weight percent glyceryl monostearate, about 5 weight percent caprylic/capric triglyceride, about 8 weight percent mineral oil and sorbic acid preservative adjusted to a pH of about 4.5 to 5Ø
10. A process for producing a cream composition according to claim 6, 7 or 8, comprising:
a) melting a mixture of the polyethylene glycol ester, glyceryl or propylene monostearate, triglyceride and mineral oil;
b) adding an aqueous solution of the preservative with mixing to form an emulsion;
c) adding meclofenamic acid to the emulsion with agitation; and d) adjusting the pH to 4.5 to 5Ø
a) melting a mixture of the polyethylene glycol ester, glyceryl or propylene monostearate, triglyceride and mineral oil;
b) adding an aqueous solution of the preservative with mixing to form an emulsion;
c) adding meclofenamic acid to the emulsion with agitation; and d) adjusting the pH to 4.5 to 5Ø
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48597383A | 1983-04-18 | 1983-04-18 | |
| US485,973 | 1983-04-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1229554A true CA1229554A (en) | 1987-11-24 |
Family
ID=23930121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000448165A Expired CA1229554A (en) | 1983-04-18 | 1984-02-23 | Meclofenamic acid topical pharmaceutical composition |
Country Status (8)
| Country | Link |
|---|---|
| AU (1) | AU560035B2 (en) |
| BE (1) | BE899366A (en) |
| CA (1) | CA1229554A (en) |
| DE (1) | DE3414377A1 (en) |
| FR (1) | FR2544198B1 (en) |
| GB (1) | GB2138287B (en) |
| NL (1) | NL8400933A (en) |
| NZ (1) | NZ207874A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1216233B (en) * | 1986-07-02 | 1990-02-22 | Menarini Sas | USE OF THE PHARMACEUTICAL FORM 'GEL' CONTAINING N (2,6 DICHLORO M TOLIL) ANTRANILIC ACID (MECLOFENAMIC ACID) APPLICABLE IN THERAPY FOR TOPICAL USE. |
| JPH01503705A (en) * | 1986-08-18 | 1989-12-14 | ビオタ・シャンティフィック・マネージメント・ピーティーワイ・リミテッド | Stimulation of angiogenesis and enhancement of endothelialization |
| US5332577A (en) * | 1988-12-27 | 1994-07-26 | Dermamed | Transdermal administration to humans and animals |
| US5241925A (en) * | 1988-12-27 | 1993-09-07 | Dermamed | Apparatus and techniques for administering veterinary medicaments |
| US5324521A (en) * | 1989-12-18 | 1994-06-28 | Dermamed | Systems for transdermal administration of medicaments |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2629884A1 (en) * | 1975-07-04 | 1977-01-20 | Gaba Ag | ORAL AND DENTAL CARE PRODUCTS |
| US4185100A (en) * | 1976-05-13 | 1980-01-22 | Johnson & Johnson | Topical anti-inflammatory drug therapy |
| NL175882C (en) * | 1977-03-28 | Procter & Gamble | PHARMACEUTICAL PREPARATION CONTAINING AN ANTI-INFLAMMATORY COMPOUND. | |
| JPS5826815A (en) * | 1981-08-10 | 1983-02-17 | Ikeda Mohandou:Kk | Nonsteroid antiphlogistic ointment and its preparation |
-
1984
- 1984-02-23 CA CA000448165A patent/CA1229554A/en not_active Expired
- 1984-02-29 AU AU25148/84A patent/AU560035B2/en not_active Ceased
- 1984-03-22 FR FR8404440A patent/FR2544198B1/en not_active Expired
- 1984-03-23 NL NL8400933A patent/NL8400933A/en not_active Application Discontinuation
- 1984-04-06 BE BE6/47951A patent/BE899366A/en not_active IP Right Cessation
- 1984-04-11 GB GB08409412A patent/GB2138287B/en not_active Expired
- 1984-04-16 DE DE19843414377 patent/DE3414377A1/en not_active Withdrawn
- 1984-04-17 NZ NZ20787484A patent/NZ207874A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NL8400933A (en) | 1984-11-16 |
| NZ207874A (en) | 1987-01-23 |
| GB2138287A (en) | 1984-10-24 |
| BE899366A (en) | 1984-10-08 |
| DE3414377A1 (en) | 1984-11-15 |
| FR2544198A1 (en) | 1984-10-19 |
| AU560035B2 (en) | 1987-03-26 |
| FR2544198B1 (en) | 1987-11-20 |
| AU2514884A (en) | 1984-10-25 |
| GB2138287B (en) | 1986-03-05 |
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