CA1049409A - Preparation of steroid-neomycin topical composition - Google Patents
Preparation of steroid-neomycin topical compositionInfo
- Publication number
- CA1049409A CA1049409A CA224,302A CA224302A CA1049409A CA 1049409 A CA1049409 A CA 1049409A CA 224302 A CA224302 A CA 224302A CA 1049409 A CA1049409 A CA 1049409A
- Authority
- CA
- Canada
- Prior art keywords
- weight
- neomycin
- steroid
- betamethasone
- benzoate
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A B S T R A C T
A novel composition incorporating a topically active steroid and neomycin is disclosed. This composition is typically prepared by gelling an alcoholic solution of the steroid with hydroxypropyl methylcellulose and add-ing thereto an aqueous solution of a neomycin salt. The pH may be adjusted to 4-5.
A novel composition incorporating a topically active steroid and neomycin is disclosed. This composition is typically prepared by gelling an alcoholic solution of the steroid with hydroxypropyl methylcellulose and add-ing thereto an aqueous solution of a neomycin salt. The pH may be adjusted to 4-5.
Description
o~
The present invention relates to a process for the production of a pharmaceutical composition suitable for topical application incorporating a topically active steroid and a topically active antimicrobial agent. More particularly, the present invention relates ~o a process for the production of a composition incorporating a topically active steroid such as 17~-benzoyl-oxy-9~-fluoro-16~-methyl-~1'4-pregnadiene~ ,21-diol-3,20-dione hereinaEter referred to as betamethasone 17-benzoate, and a salt of neomycin, typically neomycin sulfate.
The use of topically active steroid to treat local inflammatory conditions is a well accepted therapeutic procedure. Generally, the steroid is suspended or dissolved in a base for application to the inflamed site. In instances where inflammation is complicated by bacterial infections, a topical- -~
ly active antimicrobial agent is combined with the steroid to ccmbat bacterial infections. ;
Betamethasone 17-benzoate is a recently discovered topical steroid, the prepa~ation of which is for instance described in our British specifica-~ tion No. 1,191,965 published September 16, 1970, and our United States Patent : 3,529,060 issued September 15, 1970.
- ~ In order to use this compound and to provide maximwm topical effect of the steroid, a novel ointment base was produced. This forms the basis of our British complete specification No. 1,316,556 issued February 11, 1912. Briefly, the base disclosed comprises ethanol and propylene glycol, gelled by the incorporation of a carboxy vinyl polymer neutralized with an amine. This forms a clear gel with the steroid. It is applied topically and ~ permits maximum absorption of the steroid. However, when such a base contain-; ~ ing the sterold is used to include an antimicrobial agent such as neomycin sulfate, a coagulated precipitate forms. This is obviously undesirable.
More lmportantly, in actual microbiological assay by the standard agar cup method there was no available neomycin sulfate to provide the desired anti-microbial activity.
~ .
1~49409 We have now discovered how to prepare a new base containing a topically active steroid and a salt o neomycin. In accordance with the inven-tion, there is provided a process for the production of a pharmaceutical com-position suitable for topical application in the form of a clear stable aqueous gel incorporating a ~opically active steroid and a pharmaceutically accept-able salt of neomycin, which comprises the steps of: -A. dissolving said steroid in a solvent consisting essentially of a topically acceptable polyol and from 0 to 25% by weight, based on the weight of the composition, of a topically acceptable alcohol;
B. adding to the glycol solution of step A. from 0.5 % to 5 % by weight based on the weight of the final composition, of a cellulose ingredi-ent selected from the group consisting of hydroxypropyl cellulose and hydroxy-propyl methylcellulose;
C. adding to the product of step B. an aqueous solution of neo-mycin salt; and, where the neomycin salt is other than neomycin hydrochloride;
D. adding a pharmaceutically acceptable source of chloride ion in an amount sufficient to produce a clear gel.
In step A there may be present a topically acceptable alcoholic solvent such as isopropyl alcohol, ethyl alcohol or the like. Preferably the steroid is dissolved in above 20% to about 60% by weight of the polyol containing from 0% to about 25% by weight of the alcohol. Still more prefer-ably, the solvent for the steroid is a mixture of about 35% propylene glycol :
and about 15% ethyl alcohol. The percentages are based on the weight of the inal composition. ~Iydroxypropyl methylcellulose is the preferred cellulose ingredient. Suitably, the polyol is glycerin, ethylene glycol, propylene : I :
glycol, butylene glycol or the like. The source of chloride ion may be an alkall metal chloride such as sodium chloride. However, when neomycin hydro-chloride is~employed as the neomycin salt, the step of adding further chloride ` may be unnecessary. The pH of the final composition may be adjusted if ne-cessary to about ~.0 to 5.0 with a suitable acid, such as hydrochloric acid.
In the process of this invention, about 0.5 to about 5.0%, prefer-, ;. .. . .
.. ,: ,~
~-l - 2 -: i ~o~9~o~
ably up to 3.0% by weight of the cellulose ingredient is used, depending on the viscosity of the cellulose ingredient. Typically about 1.5% by weight of hydroxypropyl methylcellulose having a viscosity of about 80 to 120,000 centipoises is used. The neomycin usually is employed as its sulfate salt and preferably a sufficient amount is used so as to give a concentration of about 0.35% by weight of neomycin base in the fina] formulation.
In order to improve the consistency of the final composition, polyethylene glycol 4000 or other suitable stiffening agents known to the pharmacist's art may be included. Typically 1 to 2% by weight of polyethylene .
glycol ~000 may be added.
When a composition, produced in accordance with the foregoing process, is assayed not only is the steroid totally available, but also the neomycin is not inactivated.
In order to prevent oxidation a small amount of a suitable anti-oxidant such as 0.1% by weight of sodium bisulfi~e, and also a chelating agent may be included in the composition.
The resultlng gel is substantially clear and has a substantially uniform conslstency and iS further characterized by the fac~ that it is self-preserving in that there is no need to include in the composition the usual preservatives such as the parabens.
In order to further illustrate the practice of this invention the following examples are included:
An 0.025% by weight of betamethasone 17-benzoate is prepared from .: : -- the following ingredients:
`::: :
.~' ' ., .,, ,, ' .
~ 3 ~ `
'~ q ~.'' :' ~; :
, - : : . . . : .
~L~494~9 % Ingredients 1000.00 g .025 1. Betamethasone 17-benzoate*0.2625 .35 2. Neomycin sulfate USP, adjustt or about 5.00 g 3. Hydroxypropyl methylcellulose15.00 g 4. Propylene glycol USP 350.00 g 5. Alcohol USP **166.67 g 6. Polyethylene glycol 4000USP10.00 g 7. Disodium Edetate USP 1.00 g 8. Sodium Bisulfite USP 1.00 g 9. Sodium Chloride USP granular10.00 g 10. Hydrochloric Acid N/l q.s. or about 3.00 m 11. Water~ Purified USP q.s. to1000.00 g *5% excess for processing losses ~ adjust to give 0.35% by weight as neomycin base **11% excess for manufacturing losses The gel is prepared by dissolving betamethasone 17-benzoate in the alcohol and propylene glycol employing a suitable mixer. To this is added the hydroxy propyl methylcellulose. It is mixed until the methylcellulose is wetted.
In a separate vessel neomycin sulfate is mixed together with poly-ethylene glycol 4000, the disodium edetate and sodium bisulfite and approxi~
20mately 400 grams of water. When the solution is complete, it is added to the betamethasone 17-benzoate solution. The sodiu~ chloride dissolved in -~
approximately 40 grams of water is added to the resulting mixture. With mix- ~;
ing, the pH is then adjusted with hydrochloric acid to about 4.0 to 5Ø
Sufficient water is added to make 1000 grams. There is obtained a clear gel , containing 0.025% by weight of betamethasone 17-benzoate and 0.35% by weight of neomycin.
By employing the procedure described in Example 1 but substituting fluocinolone acetonlde for the betamethasone 17-benzoate, a clear gel is also -30obtained.
_ , .
1(1494~9 ~ ~
The biological activity of the gel produced in accordance with Example 1 is compared with an aqueous solution of neomycin sulfate. The test procedure utilized is the agar cup method utilizing S. aureus ATCC 6538P as the test organism. The following results were obtained:
Zone of Zone of FormulationInhibition ¦ Neomycin Base Inhibition ;
(mm)* (mcg/ml) (mm)*
Composition of Example 1 8.6 l 3,500 8.0 Placebo N.Z.** ¦ 3,000 7.8 1 2,500 7.4 1 2,000 7.1 1,000 6.7 500 5.9 250 5.2
The present invention relates to a process for the production of a pharmaceutical composition suitable for topical application incorporating a topically active steroid and a topically active antimicrobial agent. More particularly, the present invention relates ~o a process for the production of a composition incorporating a topically active steroid such as 17~-benzoyl-oxy-9~-fluoro-16~-methyl-~1'4-pregnadiene~ ,21-diol-3,20-dione hereinaEter referred to as betamethasone 17-benzoate, and a salt of neomycin, typically neomycin sulfate.
The use of topically active steroid to treat local inflammatory conditions is a well accepted therapeutic procedure. Generally, the steroid is suspended or dissolved in a base for application to the inflamed site. In instances where inflammation is complicated by bacterial infections, a topical- -~
ly active antimicrobial agent is combined with the steroid to ccmbat bacterial infections. ;
Betamethasone 17-benzoate is a recently discovered topical steroid, the prepa~ation of which is for instance described in our British specifica-~ tion No. 1,191,965 published September 16, 1970, and our United States Patent : 3,529,060 issued September 15, 1970.
- ~ In order to use this compound and to provide maximwm topical effect of the steroid, a novel ointment base was produced. This forms the basis of our British complete specification No. 1,316,556 issued February 11, 1912. Briefly, the base disclosed comprises ethanol and propylene glycol, gelled by the incorporation of a carboxy vinyl polymer neutralized with an amine. This forms a clear gel with the steroid. It is applied topically and ~ permits maximum absorption of the steroid. However, when such a base contain-; ~ ing the sterold is used to include an antimicrobial agent such as neomycin sulfate, a coagulated precipitate forms. This is obviously undesirable.
More lmportantly, in actual microbiological assay by the standard agar cup method there was no available neomycin sulfate to provide the desired anti-microbial activity.
~ .
1~49409 We have now discovered how to prepare a new base containing a topically active steroid and a salt o neomycin. In accordance with the inven-tion, there is provided a process for the production of a pharmaceutical com-position suitable for topical application in the form of a clear stable aqueous gel incorporating a ~opically active steroid and a pharmaceutically accept-able salt of neomycin, which comprises the steps of: -A. dissolving said steroid in a solvent consisting essentially of a topically acceptable polyol and from 0 to 25% by weight, based on the weight of the composition, of a topically acceptable alcohol;
B. adding to the glycol solution of step A. from 0.5 % to 5 % by weight based on the weight of the final composition, of a cellulose ingredi-ent selected from the group consisting of hydroxypropyl cellulose and hydroxy-propyl methylcellulose;
C. adding to the product of step B. an aqueous solution of neo-mycin salt; and, where the neomycin salt is other than neomycin hydrochloride;
D. adding a pharmaceutically acceptable source of chloride ion in an amount sufficient to produce a clear gel.
In step A there may be present a topically acceptable alcoholic solvent such as isopropyl alcohol, ethyl alcohol or the like. Preferably the steroid is dissolved in above 20% to about 60% by weight of the polyol containing from 0% to about 25% by weight of the alcohol. Still more prefer-ably, the solvent for the steroid is a mixture of about 35% propylene glycol :
and about 15% ethyl alcohol. The percentages are based on the weight of the inal composition. ~Iydroxypropyl methylcellulose is the preferred cellulose ingredient. Suitably, the polyol is glycerin, ethylene glycol, propylene : I :
glycol, butylene glycol or the like. The source of chloride ion may be an alkall metal chloride such as sodium chloride. However, when neomycin hydro-chloride is~employed as the neomycin salt, the step of adding further chloride ` may be unnecessary. The pH of the final composition may be adjusted if ne-cessary to about ~.0 to 5.0 with a suitable acid, such as hydrochloric acid.
In the process of this invention, about 0.5 to about 5.0%, prefer-, ;. .. . .
.. ,: ,~
~-l - 2 -: i ~o~9~o~
ably up to 3.0% by weight of the cellulose ingredient is used, depending on the viscosity of the cellulose ingredient. Typically about 1.5% by weight of hydroxypropyl methylcellulose having a viscosity of about 80 to 120,000 centipoises is used. The neomycin usually is employed as its sulfate salt and preferably a sufficient amount is used so as to give a concentration of about 0.35% by weight of neomycin base in the fina] formulation.
In order to improve the consistency of the final composition, polyethylene glycol 4000 or other suitable stiffening agents known to the pharmacist's art may be included. Typically 1 to 2% by weight of polyethylene .
glycol ~000 may be added.
When a composition, produced in accordance with the foregoing process, is assayed not only is the steroid totally available, but also the neomycin is not inactivated.
In order to prevent oxidation a small amount of a suitable anti-oxidant such as 0.1% by weight of sodium bisulfi~e, and also a chelating agent may be included in the composition.
The resultlng gel is substantially clear and has a substantially uniform conslstency and iS further characterized by the fac~ that it is self-preserving in that there is no need to include in the composition the usual preservatives such as the parabens.
In order to further illustrate the practice of this invention the following examples are included:
An 0.025% by weight of betamethasone 17-benzoate is prepared from .: : -- the following ingredients:
`::: :
.~' ' ., .,, ,, ' .
~ 3 ~ `
'~ q ~.'' :' ~; :
, - : : . . . : .
~L~494~9 % Ingredients 1000.00 g .025 1. Betamethasone 17-benzoate*0.2625 .35 2. Neomycin sulfate USP, adjustt or about 5.00 g 3. Hydroxypropyl methylcellulose15.00 g 4. Propylene glycol USP 350.00 g 5. Alcohol USP **166.67 g 6. Polyethylene glycol 4000USP10.00 g 7. Disodium Edetate USP 1.00 g 8. Sodium Bisulfite USP 1.00 g 9. Sodium Chloride USP granular10.00 g 10. Hydrochloric Acid N/l q.s. or about 3.00 m 11. Water~ Purified USP q.s. to1000.00 g *5% excess for processing losses ~ adjust to give 0.35% by weight as neomycin base **11% excess for manufacturing losses The gel is prepared by dissolving betamethasone 17-benzoate in the alcohol and propylene glycol employing a suitable mixer. To this is added the hydroxy propyl methylcellulose. It is mixed until the methylcellulose is wetted.
In a separate vessel neomycin sulfate is mixed together with poly-ethylene glycol 4000, the disodium edetate and sodium bisulfite and approxi~
20mately 400 grams of water. When the solution is complete, it is added to the betamethasone 17-benzoate solution. The sodiu~ chloride dissolved in -~
approximately 40 grams of water is added to the resulting mixture. With mix- ~;
ing, the pH is then adjusted with hydrochloric acid to about 4.0 to 5Ø
Sufficient water is added to make 1000 grams. There is obtained a clear gel , containing 0.025% by weight of betamethasone 17-benzoate and 0.35% by weight of neomycin.
By employing the procedure described in Example 1 but substituting fluocinolone acetonlde for the betamethasone 17-benzoate, a clear gel is also -30obtained.
_ , .
1(1494~9 ~ ~
The biological activity of the gel produced in accordance with Example 1 is compared with an aqueous solution of neomycin sulfate. The test procedure utilized is the agar cup method utilizing S. aureus ATCC 6538P as the test organism. The following results were obtained:
Zone of Zone of FormulationInhibition ¦ Neomycin Base Inhibition ;
(mm)* (mcg/ml) (mm)*
Composition of Example 1 8.6 l 3,500 8.0 Placebo N.Z.** ¦ 3,000 7.8 1 2,500 7.4 1 2,000 7.1 1,000 6.7 500 5.9 250 5.2
2 6 ~_ 10 2.1 * Average of two observations '' ** No zone ; ~ The placebo utilized in the above test comprises all the ingredients except neomycin and~betamethasone 17-benzoate. The above results show that utlll~zing the process of this invention the neomycin sulfate retains its ant mlcrobial activlty as the zone of inhi~ition approximates the zone of inhibit- `
ion produced by an aqueous solution of neomycin sulfate.
In order to illustrate the clinical effectiveness o:E the composi-tion a double blind study involving 10 normal adults was made. The two pre-_ 5 -',~ ' ' -, . . ' .
94~9 parations labeled A and B were applied to the volar aspects o~ the forearms of 10 patients in random fashion, three applications of each preparation being made to each patient.
The arms were then covered for 20 hours and the areas were then read one hour and eight hours after the removal of the covering.
Blanching of an area, i.e.~ vasoconstriction was regarded as positive, i.e., absorption of the steroid had occurred. I`he results obtained were as follows:
TOTAL NO. OF NUMBERS WITH POSITIVF.
APPLICATIONS BLANCHING
1 Hour 8 Hours S~MMARY:
Patients receiving preparation A in the 20 hour test . ~23 showed positive 1 hour after uncoverm g: l 7 showed negative 27 showed positive 8 hours after uncovering: 3 sho~ed negative Patients receiving preparation B in the 20 hour test:
. ~19 sho~ed positive 1 hour after uncoVerlng: l 11 showed negative r 2~ showed positive 8 hours after uncover m g: l 6 showed negative Preparation A utilized in the above test contained betamethasone 2017-benzoate in a gel formulation previously known. Preparation B was prepared in accordance with the process of Example 1.
From the foregoing results, it is clearly shown that in utilizing the present process the addition of neomycin did not inactivate or interfere with the absorption of the steroid~ and moreover the neomycin retained its activity.
-~
.... .. ~ . . . . :
ion produced by an aqueous solution of neomycin sulfate.
In order to illustrate the clinical effectiveness o:E the composi-tion a double blind study involving 10 normal adults was made. The two pre-_ 5 -',~ ' ' -, . . ' .
94~9 parations labeled A and B were applied to the volar aspects o~ the forearms of 10 patients in random fashion, three applications of each preparation being made to each patient.
The arms were then covered for 20 hours and the areas were then read one hour and eight hours after the removal of the covering.
Blanching of an area, i.e.~ vasoconstriction was regarded as positive, i.e., absorption of the steroid had occurred. I`he results obtained were as follows:
TOTAL NO. OF NUMBERS WITH POSITIVF.
APPLICATIONS BLANCHING
1 Hour 8 Hours S~MMARY:
Patients receiving preparation A in the 20 hour test . ~23 showed positive 1 hour after uncoverm g: l 7 showed negative 27 showed positive 8 hours after uncovering: 3 sho~ed negative Patients receiving preparation B in the 20 hour test:
. ~19 sho~ed positive 1 hour after uncoVerlng: l 11 showed negative r 2~ showed positive 8 hours after uncover m g: l 6 showed negative Preparation A utilized in the above test contained betamethasone 2017-benzoate in a gel formulation previously known. Preparation B was prepared in accordance with the process of Example 1.
From the foregoing results, it is clearly shown that in utilizing the present process the addition of neomycin did not inactivate or interfere with the absorption of the steroid~ and moreover the neomycin retained its activity.
-~
.... .. ~ . . . . :
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of a pharmaceutical composition suit-able for topical application in the form of a clear stable aqueous gel incor-porating a topically active steroid and a pharmaceutically acceptable salt of neomycin, which comprises the steps of:
A. dissolving said steroid in a solvent consisting essentially of a topically acceptable polyol and from 0 to 25% by weight, based on the weight of the composition, of a topically acceptable alcohol;
B. adding to the glycol solution of step A. from 0.5 % to 5 % by weight based on the weight of the final composition, of a cellulose ingredi-ent selected from the group consisting of hydroxypropyl cellulose and hydroxy-propyl methylcellulose;
C. adding to the product of step B. an aqueous solution of neo-mycin salt; and, where the neomycin salt is other than neomycin hydrochloride;
D. adding a pharmaceutically acceptable source of chloride ion, in an amount sufficient to produce a clear gel.
A. dissolving said steroid in a solvent consisting essentially of a topically acceptable polyol and from 0 to 25% by weight, based on the weight of the composition, of a topically acceptable alcohol;
B. adding to the glycol solution of step A. from 0.5 % to 5 % by weight based on the weight of the final composition, of a cellulose ingredi-ent selected from the group consisting of hydroxypropyl cellulose and hydroxy-propyl methylcellulose;
C. adding to the product of step B. an aqueous solution of neo-mycin salt; and, where the neomycin salt is other than neomycin hydrochloride;
D. adding a pharmaceutically acceptable source of chloride ion, in an amount sufficient to produce a clear gel.
2. A process according to claim 1 wherein the neomycin salt is neo-mycin sulfate.
3. A process according to claim 1 wherein the source of chloride ion is sodium chloride.
4. A process according to claim 1, 2 or 3 in which the steroid is betamethasone 17-benzoate.
5. A process according to claim 1 wherein from about 20% to about 60% by weight of a polyol solvent selected from the group consisting of glycerin, ethylene glycol, propylene glycol and butylene glycol is used in admixture with from about 0 to about 25% by weight of an alcoholic solvent selected from the group consisting of isopropyl alcohol and ethyl alcohol;
and wherein from about .05% to about 3% by weight of a hydroxypropyl methyl-cellulose is used; all percentages being based on the weight of the final composition.
and wherein from about .05% to about 3% by weight of a hydroxypropyl methyl-cellulose is used; all percentages being based on the weight of the final composition.
6. A process according to claim 5 in which 0.025% by weight, based on the weight of the final composition of betamethasone 17-benzoate is em-ployed.
7. A process for the production of a stabilized betamethasone 17-benzoate and neomycin sulfate composition suitable for topical application comprising the steps of:
A. dissolving 0.025% by weight of betamethasone 17-benzoate in approximately 15% by weight of ethanol and 35% by weight of propylene glycol;
B. adding to the solvent solution so obtained about 1.5% by weight of hydroxypropyl methylcellulose having a viscosity of from about 80 to about 120,000 centipoises;
C. dissolving in water about 0.5% by weight of neomycin sulfate in a solution containing 1% by weight of polyethylene glycol 4000 and 40% by weight of water and adding the solution to the product of step B;
D. adding sufficient sodium chloride to ensure solution of the neomycin sulfate; and E. adjusting the pH of this resulting mixture to about 4.0 to about 5.0; all percentages being based on the weight of the final composition.
A. dissolving 0.025% by weight of betamethasone 17-benzoate in approximately 15% by weight of ethanol and 35% by weight of propylene glycol;
B. adding to the solvent solution so obtained about 1.5% by weight of hydroxypropyl methylcellulose having a viscosity of from about 80 to about 120,000 centipoises;
C. dissolving in water about 0.5% by weight of neomycin sulfate in a solution containing 1% by weight of polyethylene glycol 4000 and 40% by weight of water and adding the solution to the product of step B;
D. adding sufficient sodium chloride to ensure solution of the neomycin sulfate; and E. adjusting the pH of this resulting mixture to about 4.0 to about 5.0; all percentages being based on the weight of the final composition.
8. A stabilized clear aqueous gel composition comprising about 0.025%
by weight betamethasone 17-benzoate, about 0.5% by weight neomycin sulfate, about 35% by weight propylene glycol, about 15% by weight ethanol, about 1.5%
by weight hydroxypropyl methylcellulose having a viscosity of from about 80 to about 120,000 centipoises, a sufficient amount of sodium chloride to pro-duce a clear gel, and a sufficient amount of hydrochloric acid to give a final pH of about 4.0 to about 5.0, produced in accordance with the process of claim 7.
by weight betamethasone 17-benzoate, about 0.5% by weight neomycin sulfate, about 35% by weight propylene glycol, about 15% by weight ethanol, about 1.5%
by weight hydroxypropyl methylcellulose having a viscosity of from about 80 to about 120,000 centipoises, a sufficient amount of sodium chloride to pro-duce a clear gel, and a sufficient amount of hydrochloric acid to give a final pH of about 4.0 to about 5.0, produced in accordance with the process of claim 7.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46025474A | 1974-04-11 | 1974-04-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1049409A true CA1049409A (en) | 1979-02-27 |
Family
ID=23827960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA224,302A Expired CA1049409A (en) | 1974-04-11 | 1975-04-10 | Preparation of steroid-neomycin topical composition |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS535729B2 (en) |
| AU (1) | AU7776275A (en) |
| CA (1) | CA1049409A (en) |
| DE (2) | DE2504615C3 (en) |
| DK (1) | DK143537C (en) |
| FR (1) | FR2267107B1 (en) |
| GB (1) | GB1455552A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984000111A1 (en) * | 1982-06-24 | 1984-01-19 | Robert Alan Smith | Pharmaceutical gel composition |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4489070A (en) * | 1983-05-13 | 1984-12-18 | Schering Corporation | Betamethasone dipropionate cream |
| DE3333240A1 (en) * | 1983-09-12 | 1985-03-28 | Schering AG, 1000 Berlin und 4709 Bergkamen | MEDIUM FOR TRANSDERMAL APPLICATION OF MEDICINAL PRODUCTS |
| AU592065B2 (en) * | 1984-10-09 | 1990-01-04 | Dow Chemical Company, The | Sustained release dosage form based on highly plasticized cellulose ether gels |
| FR2588189B1 (en) * | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | LIQUID-GEL PHASE TRANSITION PHARMACEUTICAL COMPOSITION |
| DE3614095A1 (en) * | 1986-04-25 | 1987-10-29 | Goedecke Ag | OXYALKYLCELLULOSE CONTAINING GEL PREPARATION |
| ES2078256T3 (en) * | 1990-04-05 | 1995-12-16 | Knoll Ag | PHARMACEUTICAL FORMULA FOR TOPICAL USE CONTAINING SODIUM DICLOFENACO. |
| AU2000268609A1 (en) * | 2000-09-14 | 2002-03-26 | Robert Theiler | Intraarticular agent for the treatment of osteoarthritis |
| PL2366408T3 (en) * | 2010-03-01 | 2013-01-31 | Salvat Lab Sa | Aqueous clear solutions of fluocinolone acetonide for treatment of otic inflammation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1017746B (en) * | 1954-02-09 | 1957-10-17 | Upjohn Co | Process for the preparation of free flowing, non-settling therapeutically effective suspensions |
| US3485915A (en) * | 1966-04-22 | 1969-12-23 | Revlon | Thickened hydroxypropyl cellulose compositions |
| DE2015300A1 (en) * | 1969-04-01 | 1970-10-29 | Syntex Corp., Panania;PM | topical anti-inflammatory preparations and methods of their use |
| DK135267A (en) * | 1971-02-25 |
-
1975
- 1975-01-30 AU AU77762/75A patent/AU7776275A/en not_active Expired
- 1975-02-04 DE DE19752504615 patent/DE2504615C3/en not_active Expired
- 1975-03-20 JP JP3426675A patent/JPS535729B2/ja not_active Expired
- 1975-03-21 GB GB955575A patent/GB1455552A/en not_active Expired
- 1975-04-07 DK DK147575A patent/DK143537C/en not_active IP Right Cessation
- 1975-04-07 FR FR7510763A patent/FR2267107B1/fr not_active Expired
- 1975-04-10 CA CA224,302A patent/CA1049409A/en not_active Expired
- 1975-04-10 DE DE19752515594 patent/DE2515594C3/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984000111A1 (en) * | 1982-06-24 | 1984-01-19 | Robert Alan Smith | Pharmaceutical gel composition |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2515594A1 (en) | 1975-10-30 |
| JPS535729B2 (en) | 1978-03-01 |
| GB1455552A (en) | 1976-11-17 |
| DK147575A (en) | 1975-10-12 |
| DE2504615A1 (en) | 1975-10-16 |
| DK143537C (en) | 1982-02-01 |
| DK143537B (en) | 1981-09-07 |
| FR2267107B1 (en) | 1978-07-28 |
| AU7776275A (en) | 1976-08-05 |
| DE2504615B2 (en) | 1977-07-14 |
| DE2515594C3 (en) | 1982-06-03 |
| FR2267107A1 (en) | 1975-11-07 |
| JPS50132122A (en) | 1975-10-20 |
| DE2504615C3 (en) | 1980-10-02 |
| DE2515594B2 (en) | 1978-12-07 |
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