CA1139664A - Oleaginous emollient vehicle for steroid formulations - Google Patents

Oleaginous emollient vehicle for steroid formulations

Info

Publication number
CA1139664A
CA1139664A CA000343238A CA343238A CA1139664A CA 1139664 A CA1139664 A CA 1139664A CA 000343238 A CA000343238 A CA 000343238A CA 343238 A CA343238 A CA 343238A CA 1139664 A CA1139664 A CA 1139664A
Authority
CA
Canada
Prior art keywords
weight
composition
accordance
wax
steroid
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
Application number
CA000343238A
Other languages
French (fr)
Inventor
Thomas M. Wong
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ER Squibb and Sons LLC
Original Assignee
ER Squibb and Sons LLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC
Application granted granted Critical
Publication of CA1139664A publication Critical patent/CA1139664A/en
Expired legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/342Alcohols having more than seven atoms in an unbroken chain
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

SN43 Abstract OLEAGINOUS EMOLLIENT VEHICLE FOR STEROID FORMULATIONS A novel ointment-like composition comprising not less than 40% by weight of isosteraryl alcohol is provided for the topical administration of corticosteroids.

Description

~ 4 SN43 OLEAGINOUS EMOLLIENT VEHICLE FOR STEROID FORMNLATIONS

The present invention relates to an oleaginous emollient vehicle for steroid formulations.
It is an object of this invention to provide an ointment-like vqhicle which eliminates the feeling of greasiness when applied to the skin without sacrificing the oc~lusive property of an ointment.
It is a further object of this invention to provide an ointment-like vehicle which is not affected by temper~ture extremes. More specifically, it is an object of this invention to provide a steroid vehicle which at temperatures up to 50C
does not show evidence of bleeding or syneresis, and which can be extruded from tubes at refrigerator temperatures without difficulty.
It is an object of this invention to provide an ointment-like vehicle for steroid formulations which has enhanced emolliency and improved occlusive properties.
It is an object of this invention to provide an ointment-like steroid vehicle which does not stain clothing or bedding with which it comes in contact.
It is an object of this invention to provide -9~ ;4 a vehicle for steroid formulations which will provide for uniform distribution of the steroid and enhance therapeutic efficacy.
These and other objects which will be apparent to the practitionçr of this invention can be achieved by utilizing isos$earyl alcohol in place of vegetable oil or petroleum hydrocarbons in an ointment-like vehicle. M~re sp~cifically, the isostearyl alcohol should make up at least 40% by weight of the steroid formulation .
Corticosterolds have been used for the treatment of various dermatoses when applied topically. The steroids have been formulated as creams, ointments, lotions and aerosol sprays. Of the various form~
ulations, ointments have in the past received the least patient acceptance. Ointments do, however, have the beneficial therapeutic affect of occlusiveness, a highly desirable characteristic for topical steroid therapy.
Early ointment formulations used in topical steroid therapy were based largely on fats, grease and petrolatum. Early synthetic bases for use in ointments are described in United States patent
2,627,938 and 2,628,187 which describe a petroleum oil vehicle which has been thickened with poly-ethylene. Although these vehicles have gained wide acceptance in the steroid field they do have serious disadvantages. Cosmetically they are not as elegant as patients would like. More specifically, they impart a lingering greasy feeling to the skin, which is most noticeable on hairy skin. These ointment bases are also water insoluble and, there-fore, difficult to wash off the skin. Still further, 11~9~i4
3--oil bases of the past are prone to stain garments and bedding with which they come in contact.
Aside from the cosmetic problems enumerated above, ointment bases possess serious physical stability problems when petroleum vehicles are employed. Excessive temperatures can cause softening or melting of the vehicle and result ~
in the separation of suspended components. This I
separation of suspended components (breaking down of the gel structure is a serious problem hecause uniform distribution of the active steroid ingredient is considered important for successful topical corticosteroid treatment. The steroids are not soiuble in petrolatum vehicles and, therefore, a steroid suspension is the only choice for incor-poration of the steroid into a petrolatum vehicle. -More recently, Carbowax, a mixture of poly-ethylene glycol polymers has been used as an ointment-like base. These compositions have the advantage of being water-washable, but they are still greasy and cosmetically inelegant. Further-more, Carbowax vehicles are not occlusive.
United States patent 3,592,930 issued July 13, 1971, discloses an ointment-like vehicle which is said to be water-washable and occlusive and which comprises as its essential ingredients a fatty alcohol having 16 to 24 carbon atoms and a glycol.
The glycol solvent is said to function as a solvent for a glycol-soluble drug or as a carrier for a glycol-insoluble drug. The fatty alcohol component is said to be "a solid component which naturally * Trade Mark .

il~9~4 SN43 thickens the composition".
United States patent 3~924,004 discloses a formulation comprising a saturated fatty alcohol having from 16 to 24 carbon atoms, propylene carbonate, and a glycol solvent.
In its broad~st aspect, the present invention comprises the use ~f at least 40% weight of isostearyl alcohol in a steroid formulation. The isostearyl alcohol will serve both as a principal solvent for the formulation and as an emollient. The fatty alcohols used in the prior ~rt have been the lower molecular weight fatty alcohQls in minor amounts, or when larger amounts of fatty alcohol have been used, the higher molecular weight solid fatty alcohols. While the lower molecular weight fatty alcohols are fluids they are undesirable because of their odor and because of their tendency to irritate the skin. Isostearyl alcohol Oll the other hand is a non-irritating liquid which does not have as strong an odor as its lower molecular weight homologs.
In a preferred embodiment of this invention the steroid formulation will also contain 5-12~ by weight of a high melting point wax (melting point range 60-90C), e.g., carnauba wax, candellia wax, ozokerite ;4 _5-wax, and beeswax, and 4-10~ by weight of a moderately high melting polyhydric alcohol ester of a fatty acid (melting point range 60-90C), e.g., propylene glycol distearate and ethylene glycol distearate. The wax and the polyhydric alcohol ester of a fatty acid together form a ne$work (or matrix) within which is contained the steroid partially dissolved in the isostearyl~alcohol. The formulation can also contain a simple fatty acid ester which functions as a non-greasy emollient. The emollient wiil disappear when rubbed into the skin and lends lubricity to the skin.
Exemplary of the simple fatty acid esters contemplated are isopropyl myristate and isopropyl palmitate.
Cosolvents may also be used along with the isostearyl alcohol. Particularly preferred as a cosolvent is propylene carbonate, which may be used in an amount from about 1% to 7% by weight of the formulation. When using a cosolvent it may be advan-tageous to include in the formulation a coupler.
The term "coupler" is used to describe a compound which insures the miscibility of the solvents. When propylene carbonate is used as a cosolvent with isostearyl alcohol, polyoxypropylene stearyl ether serves as an effective coupler.
To enhance the occlusive property of the ointment-like vehicle a polysiloxane such as dimethylpoly-siloxane liquid may be employed in an amount of about 5% to 10% by weight of the formulation.
The ointment-like steroid vehicle described herein can also contain various additional ingredients which are conventional in the pharmaceutical art.

9~

These additional ingredients can be used to improve the stability, homogeneity, consistency, emolliency, penetrability and the cosmetic elegance of the vehicle. The choice of particular ingredients is 5 within the level of ordinary skill in the art and the practitioner of this invention will choose the various adjuvants depending on the particular qualities he wishes the vehicle to have. For example, the art recognizes the equivalence of 1,3-butylene glycol and a simple fatty acid ester in an ointment formulation. The 1,3-butylene glycol can be used in place of all, or part, of the simple fatty acid ester as a non-greasy emollient.
A method for preparing the preferred steroid 15 formulations of this invention comprises first dissolving the steroid drug in the cosolvent. To a separate container, preferably a steam jacketed stainless steel vessel equipped with a stirrer, is added the rest of the ingredients with the exception 20 of the polysiloxane. These are melted together and stirred until a clear melt is effected. To this solution is added the steroid dissolved in the cosolvent and the resulting solution is stirred and heated. The mixture is next shock-cooled and the 25 resultant formulation is then placed in a planetary type mixer to which is added the polysiloxane ingredient. To improve the quality of the finished product, the resultant formulated mixture may he passed through a roller mill.

1~9~4 SN43 Alternately, the above-described procedure can be modified b~ including high shearing equipment in the steam ~acketed stainless steel vessel. Immediately prior to shock-cooling, the mixture of ingredients can be sub~ected to high shear. In this method, the polysiloxane ingredient can be added prior to the - high shear mixing.
The vehicle described herein is suitable for use with topical antiinflammatory steroi'ds. Exemplary Of the steroids contemplated are the acetonide derivatives of steroids of the pregnane series described in United States patent 3,048,581. Included within the steroids described by this patent are triamcinolone acetonide and halcinonide. It is emphasized that these steroids are meant to be exe~plary only and it is not meant to limit this invention to use with any particular steroid or group of topically active antiinflammatory steroids.
The steroid~ incorporated in the formulation of this invention may be present in an amount of from about 0.01% by weight t4 about 1.0% by weight, preferably from ahout 0.025% by weight to about 0.5~ by weight.
The following examples are specific embodiments of this invention.

1139~j64 Example The various ingredients set forth below are formulated into oleaginous emollient vehicles for steroid formulations. Alternative methods of formulation are s~t forth below.

Method I
The carnaub~ wax and ethylene glycol distearate are mixed with is~propyl myristate ~formulations 1-7) or 1,3-butylene g~ycol (formulations 8-14), polyoxy-propylene stearyl ether and isostearyl alcohol.
While stirring, t~e mixture is heated until the wax melts and the temperature is maintained at 80-85C for a few minutes. In a separate container, the halcinonide is-dissolved in propylene carbonate with the aid of heat. The halcinonide solution is combined with the wax mixture and the temperature of the mixture is brought to 80-85C. The molten mixture is transfqrred to a shock cooling machine and quickly cooled using water maintained in the 20-30C range. The emollient base obtained is gently heated to 35C and combined with Corning DC
200 fluid (also heated to 35C) in a planetary mixer. The emollient is then passed through a roller mill.
Method II
The carnauba wax and ethylene glycol distearate are mixed with isopropyl myristate (formulation 1-7) or 1,3-butylene glycol (formulations 8-141, polyoxy-propylene stearyl ether and isostearyl alcohol.

~ SN43 _g_ While stirring the mixture is heated until the wax melts and the temperature is maintained at 80-85C
for a few minutes. In a separate container, the ,~
halcinonide is dissolved in propylene carbonate with ~l 5 the aid of heat. The halcinonide solution is i, combined with the molten wax mixture and the Corning DC 200 Fluid is then added. The temperature of the j mixture is raised to 80-85C and the mixture is subjected to high shear stirring which is maintained until just prior to transfer to a shock cooling machine for immediate quick cooling using water maintained in the 20-30 range.

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Claims (10)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-
1. A composition for the topical administration of a corticosteroid comprising an effective amount of the cortico-steroid and not less than 40% by weight of the composition of isostearyl alcohol.
2. A composition in accordance with claim 1 further com-prising a wax having a melting point of 60° to 90°C and a poly-hydric alcohol ester of a fatty acid.
3. A composition in accordance with claim 2 wherein the wax is carnauba wax and the fatty acid ester is ethylene gly-col distearate.
4. A composition in accordance with claim 1, 2 or 3 further comprising an additional solvent.
5. A composition in accordance with claim 1, 2 or 3 further comprising propylene carbonate as an additional sol-vent.
6. A composition in accordance with claim 1, 2 or 3 further comprising about 1% by weight to 7% by weight propy-lene carbonate as an additional solvent.
7. A composition in accordance with claim 1 which in-cludes 5% by weight to 12% by weight of a wax having a melt-ing point of 60° to 90°C, and 4% by weight to 10% by weight of a polyhydric alcohol ester of a fatty acid.
8. A composition in accordance with claim 1, 2 or 3 wherein the corticosteroid is present in an amount of from about 0.01% by weight to about 1.0% by weight.
9. A composition in accordance with claim 1, 2 or 3 wherein the corticosteroid is present in an amount of from about 0.025% by weight to about 0.5% by weight.
10. A composition for the topical administration of a corticosteroid comprising from about 0.01% by weight to about 1.0% by weight of the corticosteroid, not less than 40% by weight of isostearyl alcohol, 5% by weight to 12% by weight of a wax having a melting point of 60° to 90°C, 4% by weight to 10% by weight of a polyhydric alcohol ester of a fatty acid, and about 1% by weight to 7% by weight propylene carbonate.
CA000343238A 1979-01-17 1980-01-08 Oleaginous emollient vehicle for steroid formulations Expired CA1139664A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US410079A 1979-01-17 1979-01-17
US4,100 1979-01-17

Publications (1)

Publication Number Publication Date
CA1139664A true CA1139664A (en) 1983-01-18

Family

ID=21709140

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000343238A Expired CA1139664A (en) 1979-01-17 1980-01-08 Oleaginous emollient vehicle for steroid formulations

Country Status (4)

Country Link
AU (1) AU5433480A (en)
CA (1) CA1139664A (en)
GB (1) GB2040165B (en)
ZA (1) ZA797028B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4758432A (en) * 1984-10-15 1988-07-19 Richardson-Vicks Inc. Topical treatment of skin inflammatory disorders
EP0211555A3 (en) * 1985-08-01 1988-06-08 Dow Corning Corporation Transparent silicone compositions

Also Published As

Publication number Publication date
GB2040165B (en) 1983-05-05
ZA797028B (en) 1980-11-26
AU5433480A (en) 1980-07-24
GB2040165A (en) 1980-08-28

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Effective date: 20000118