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Home , Amcinafide, Descinolone, Dichlorisone, Diflorasone, Fluperolone, Hydrocortamate

US007217422B2

(12) United States Patent (10) Patent No.: US 7,217,422 B2 Gans et al. (45) Date of Patent: May 15, 2007

(54) COMPOSITIONS AND METHODS FOR (58) Field of Classification Search ...... 514/169, ENHANCING 514/170, 172, 177-180, 171,69–180; 424/400, See application file for complete search history. (75) (56) References Cited Inventors: Eugene H. Gans, Westport, CT (US); Mitchell S. Wortzman, Scottsdale, AZ U.S. PATENT DOCUMENTS (US) 3,934,013 A 1/1976 Poulsen ...... 514,170 FOREIGN PATENT DOCUMENTS EP O 020 794. A 1, 1981 (73) Assignee: Medicis Pharmaceutical Corporation, WO WO 91.08733. A 6, 1991 Scottsdale, AZ (US) OTHER PUBLICATIONS Physicians’ Desk Reference, 51 Edition, 1997, pp. 2299-2300, for *) Notice: Subject to anyy disclaimer, the term of this example.* patent is extended or adjusted under 35 Bennett et al., “Optimization of bioavailability of topical : U.S.C. 154(b) by 382 days. non-occluded penetration enhancers under thermodynamic con trol”, Journal of Pharmacy and Pharmacology, vol. 37, No. 5, 1985, (21) Appl. No.: 10/407.354 pp. 298-304. * cited by examiner (22) Filed: Apr. 4, 2003 Primary Examiner San-Ming Hui (65) Prior Publication Data (74) Attorney, Agent, or Firm William J. McNichol, Jr.; Maryellen Feehery Hank; Reed Smith LLP US 2003/O186951 A1 Oct. 2, 2003 (57) ABSTRACT Related U.S. Application Data The present invention comprises a composition, method of (62) Division of application No. 10/037.360, filed on Dec. enhancing potency and method of delivering 21, 2001, now Pat. No. 6,765,001. in a vehicle comprising at least two penetration enhancers, and solvents and emulsifiers. The propylene glycol and (51) Int. Cl. penetration enhancers are present in ratio to the total of the A6 IK3I/56 (2006.01) propylene glycol, penetration enhancers, and solvents and A6 IK 47/44 (2006.01) emulsifiers of at least about 0.70. (52) U.S. Cl...... 424/400: 514/171; 514/180; 514/169 16 Claims, No Drawings US 7,217,422 B2 1. 2 COMPOSITIONS AND METHODS FOR disrupt the epidermal barrier and increase penetration. ENHANCING CORTICOSTEROID Hydrating the skin has also been shown to increase the DELIVERY penetration of the corticosteroids. Once absorbed through the skin, topical corticosteroids RELATED APPLICATIONS are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. The potencies of This application is a divisional of U.S. Ser. No. 10/037, corticosteroids vary greatly and it is a challenge to increase 360, filed Dec. 21, 2001 now U.S. Pat. No. 6,765,001. the potency of any particular .

FIELD OF THE INVENTION 10 BACKGROUND OF THE INVENTION

Topical corticosteroids are useful for their anti-inflamma The clinical effectiveness of corticoids is related to four tory, anti-pruritic and vasoconstrictive actions. Corticoster basic properties: vasoconstriction, antiproliferative effects, oids (or corticoids) are any steroids (lipids that contain a immunosuppression, and anti-inflammatory effects. Topical hydrogenated cyclopentoperhydrophenanthrene ring sys 15 steroids cause the capillaries in the Superficial dermis to tem) elaborated by the adrenal cortex (except sex hormones constrict, thus reducing erythema. The ability of a given of adrenal origin) in response to the release of adrenocorti agent to cause vasoconstriction usually cor cotrophin or adrenocorticotropic hormone by the pituitary relates with its anti-inflammatory potency. Vasoconstrictor gland, or to any synthetic equivalent, or to angiotensin II. assays are used in the art and by the U.S. Food and Drug Corticosteroids include but are not limited to Administration for determining the potency of topical cor dipropionate, , amcinafel, , bec ticosteroid preparations. Topical glucocorticoid preparations lamethasone, , betamethasone dipropionate, have been divided in the field into seven classes based on , propionate, chloro potency based on double-blind clinical Studies and vasocon , clocortelone, , , cortodoxone, strictor assays. Class 1 includes the most potent, while class difluorosone diacetate, , , deflupred 25 nate, dihydroxycortisone, , , 7 contains the least potent. , diacetate, , esters of The following glucocorticoid preparations were desig betamethasone, flucetonide, flucloronide, fluorocortisone, nated in Fitzpatrick, Dermatology in General Medicine, 5" flumethasone, , , edition, CD-ROM, 1999, Table 243-1, with the following classes. acetonide, flucortolone, , , 30 fluroandrenolone acetonide, , fluran drenolide, fluorametholone, propionate, hydro TABLE 1. cortisone, butyrate, , Corticosteroid , , , methylpred Preparation Corticosteroid Class Source nisone, , furoate, 35 , prednisone, , prednidone, tri Temovate (R) ClobetaSone propionate 1 GlaxoWellcome Cream O.05% amcinolone acetonide, and . Temovate (R) ClobetaSone propionate 1 GlaxoWellcome Hydrocortisone was the first corticosteroid found to be ointment 0.05% topically effective. Other more potent , Diprolene (R) Betamethasone 1 Schering Corp. cream O.O.5% dipropionate which are a subset of corticosteroids that affect carbohydrate 40 Diprolene (R) Betamethasone 1 Schering Corp. metabolism, inhibit corticotropin secretion, and possess pro ointment 0.05% dipropionate nounced anti-inflammatory activity, have since been devel Psorcon (R) 1 Dermilk oped. Currently, topical steroids are among the most fre ointment Laboratories, Inc. quently prescribed of all dermatological drug products. Cyclocort (R) Amcinonide 2 Fujisawa ointment 0.1% It is believed that glucocorticoids exert their potent anti 45 Diprolene (R) Betamethasone 2 Schering Corp. inflammatory effects by inhibiting the formation of prostag cream AF dipropionate landins and other derivatives of the arachidonic acid path O.05% Diprosone (R) Betamethasone 2 Schering Corp. way. It is known that glucocorticoids inhibit the release of ointment 0.05% dipropionate phospholipase A2, the enzyme responsible for liberating Elocon (R) Mometasome furoate 2 Schering Corp. arachidonic acid from cell membranes, thus inhibiting the 50 ointment 0.1% arachidonic acid pathway. Currently, it is believed that Florone (R) Diflorasone diacetate 2 Dermilk glucocorticoids inhibit phospholipase A2, in cells by directly ointment 0.05% Halog (R) cream 2 Westwood-Squibb inducing phosphorylation of the enzyme. O.1% Steroids are commonly divided into two classes, fluori Lidex (R) gel Fluocinonide 2 Medicis Pharma nated and nonfluorinated. Fluorinated steroids have been 55 O.05% ceuticals Corp. Lidex (R) cream Fluocinonide 2 Medicis Pharma chemically modified to increase potency. These modifica O.05% ceuticals Corp. tions, such as halogenation and methylation, can result in Lidex (R) Fluocinonide 2 Medicis Pharma improved activity within the target cell and in decreased ointment 0.05% ceuticals Corp. breakdown to inactive metabolites. These modifications can Maxiflor (R) Diflorasone diacetate 2 Allergan Herbert ointment 0.05% also lead to more systemic side effects. However, modifi 60 Topicort (R) DeSoximetaSone 2 Medicis Pharma cation of the chemical structure of the steroid is not the only cream 0.25% ceuticals Corp. way to increase potency. Topicort (R) gel DeSoximetaSone 2 Medicis Pharma The potency of preparations is strongly O.05% ceuticals Corp. Topicort (R) DeSoximetaSone 2 Medicis Pharma correlated to their absorption through the skin. Treatment of ointment 0.25% ceuticals Corp. the skin prior to application of the topical steroid may also 65 Aristocort A (R) 3 Fujisawa affect the absorption of the compounds into the skin. Treat ointment 0.1% ments with keratolytics or with fat solvents (such as acetone) US 7,217,422 B2 3 4 loneR cream or ointment of Schering and Class 1 Psorcon R TABLE 1-continued ointment of Dermik Laboratories, Inc. Corticosteroid Several factors such as the vehicle, the integrity of the Preparation Corticosteroid Class Source epidermal barrier, and the use of occlusive dressings affect the percutaneous absorption and resulting potency of corti Cultivate (R) 3 GlaxoWellcome ointment costeroids regardless of the intrinsic potency of the gluco O.005% corticosteroid (or glucocorticoid) molecule. Further, inflam Cyclocort (R) Amcinonide 3 Fujisawa mation and/or other disease processes in the skin increase cream 0.1% Cyclocort (R) Amcinonide 3 Fujisawa 10 percutaneous absorption. Lotion 0.1% The vehicle in which the corticoid is incorporated may be Diprosone (R) Betamethasone 3 Schering Corp. cream O.O.5% dipropionate as important as the corticoid molecule itself in determining Florone (R) cream Diflorasone diacetate 3 Dermilk the potency of a given formulation because the vehicle O.05% affects the amount of corticoid that is released in any given Halog (R) Halcinonide 3 Westwood-Squibb 15 ointment 0.1% period of time, and its absorption. In many corticosteroid Lidex (R) E Fluocinonide 3 Medicis Pharma compositions, the vehicle is as much as 99% of the total cream O.O.5% ceutical Corp. composition. Very occlusive vehicles, such as ointments Maxiflor (R) Diflorasone diacetate 3 Allergan Herbert cream O.O.5% (water-insoluble mixtures of oil and petrolatum), increase Vallisone (R) Betamethasone valerate 3 Schering Corp. the corticosteroid effect because they provide increased ointment 0.1% hydration of the stratum corneum and increase the skin's Cordran (R) Flurandrenolide 4 Oclassen permeability. By covering the skin with an occlusive dress ointment 0.05% Elocon (R) cream Mometasome furoate 4 Schering Corp. ing Such as plastic wrap, this effect can be heightened as O.1% much as 100-fold. The solubility of the corticoid in the Kenalog (R) Triamcinolone acetonide 4 Westwood-Squibb vehicle also affects penetration into the skin. cream 0.1% 25 Synalar (R) Fluocinolone acetonide 4 Medicis Pharma Creams, which are suspensions of oil in water, have also ointment ceuticals Corp. been used as vehicles for corticosteroids. The compositions O.025% Westcort (R) Hydrocortisone valerate 4 Westwood-Squibb of creams vary and are far less greasy than ointments but do ointment 0.2% not provide the same degree of hydration to the skin, and Cordran (R) Furandrenolide 5 Oclassen 30 therefore may not have as high penetration as ointments. cream O.O.5% Lotions, which are suspensions of oil in water and are Cultivate (R) FluticasOne propionate 5 GlaxoWellcome cream O.O.5% similar to creams, are vehicles which include agents to help Diprosone (R) Betamethasone 5 Schering Corp. solubilize the corticosteroids. Solutions have been used as lotion 0.05% dipropionate vehicles and are water based with propylene glycol. Gels are Kenalog (R) Triamcinolone acetonide 5 Westwood-Squibb 35 lotion 0.1% Solid components at room temperature but melt on the skin. Locoid (R) cream 5 Ferndale Lotions, gels and solutions have less penetration than oint O.1% mentS. Synalar (R) cream Flucinolone acetonide 5 Medicis Pharma O.025% ceuticals Corp. Many vehicles for corticosteroids include propylene gly Vallisone (R) Betamethasone valerate 5 Schering Corp. 40 col for dissolving the corticosteroid in the vehicle. In gen cream 0.1% eral, compositions that contain higher amounts of propylene Westcort (R) Hydrocortisone valerate 5 Westwood-Squibb cream 0.2% glycol tend to be more potent. Aclovate (R) AlclometaSone 6 GlaxoWellcome Vehicles are so important in the potency of corticosteroids cream O.O.5% dipropionate Aclovate (R) AlclometaSone 6 GlaxoWellcome that different formulations containing the same amount of ointment 0.05% dipropionate 45 the same corticosteroid often are in different potency classes. Aristocort (R) Triamcinolone acetonide 6 Fujisawa For example, commercially available preparations of 0.05% cream 0.1% Desowen (R) Desonide 6 Galderma betamethasone dipropionate are classified as having Class 1. cream O.O.5% Class 2 or Class 3 potency, depending on their vehicles (as Synalar (R) Fluocinolone acetonide 6 Medicis Pharma seen in Table 1). solution 0.01% ceuticals Corp. 50 Synalar (R) Fluocinolone acetonide 6 Medicis Pharma cream 0.01% ceuticals Corp. SUMMARY OF THE INVENTION Tridesilon (R) Desonide 6 Miles cream O.O.5% Vallisone (R) Betamethasone valerate 6 Schering Corp. The present invention comprises a novel vehicle which is lotion 0.1% 55 safe for topical application, stable, and provides increased Topicals with potency for corticosteroid preparations, especially fluori hydrocortisone nated corticosteroids. dexamethasone, flumethasone, An embodiment of the present invention delivers the prednisolone, and corticosteroid in a vehicle that comprises a corticosteroid, methylprednisol 60 and (a) at least two penetration enhancers, including propy Ole lene glycol, dimethyl isosorbide or diisopropyl adipate, (b) solvents and/or emulsifiers for the corticosteroid and option All percentages given are weight percentages unless otherwise noted. ally the penetration enhancers and (c) optionally, non solvent/emulsifier ingredients. The vehicle has a ratio of Although there is no significant difference between poten 65 a:(a+b) that is greater than or equal to 0.70, preferably cies within Class 2, within Class 1 Temovate R cream or greater than or equal to 0.80 and most preferably greater ointment is significantly more potent than Class 1 Dipro than or equal to 0.90 or 0.95. US 7,217,422 B2 5 6 DETAILED DESCRIPTION OF THE Soap and water. Skin vasoconstrictor evaluations were per PREFERRED EMBODIMENTS formed on a four point scale (0–3) at approximately 18 hours after application. The present invention enhances the potency of corticos Scores for skin vasoconstriction were Summed for each teroid preparations with a vehicle comprising at least two composition (each composition was applied to thirty-six penetration enhancers, including diisopropyl adipate, dim volunteers and those thirty-six scores were summed). For each composition tested, the ratio of penetration enhancers ethyl isosorbide, propylene glycol, 1.2.6-hexanetriol, and (a) to the Sum of penetration enhancers, and solvents and benzyl alcohol. The corticosteroids with which this inven emulsifiers (a+b) was calculated (a:(a+b)). All of the com tion may be used include, but are not limited to, fluorinated 10 corticosteroids. positions comprise 0.10% fluocinonide. Another embodiment of the present invention is a method TABLE 2 for enhancing the potency of corticosteroids, preferably fluorinated corticosteroids. The corticosteroid is combined Range of 1- O.94 O.89- O.79- O.69 0.59– a: (a + b) O.9S O.90 O.80 O.70 O.60 OSO with two or more penetration enhancers (preferably propy 15 lene glycol and at least one other penetration enhancer), and Average of 93 85 71 72 62 58 one or more solvents and emulsifiers for the corticosteroid Summed Vasoconstrictor and optionally penetration enhancers, wherein the penetra Scores tion enhancers are present in ratio to the total of the penetration enhancers, and solvents and emulsifiers of at * means there were no samples with the range of 0.59 to 0.55. least about 0.70, preferably at least 0.80 and most preferably As seen in the above table, the average vasoconstrictor 0.90 or 0.95. Optionally, one or more inactive ingredients scores are significantly lower for ranges of a:(a+b)-0.70. may also be combined with the corticosteroid. The corticosteroid preparations with average vasoconstrictor Another embodiment of the present invention is a method 25 scores of 58 and 62 are significantly less potent than those of delivering corticosteroids to skin, nails or hair, preferably preparations with average vasoconstrictor scores of 72 and mammalian skin, most preferably human, dog or cat skin. higher. Scores of 62 and 58 are not significantly different. The corticosteroids are preferably fluorinated corticoster oids. The corticosteroid is combined with two or more This magnitude of increase in vasoconstrictor scores is penetration enhancers, and one or more solvents and emul typical of an increase in class. sifiers for the corticosteroid, wherein the penetration 30 Several control compositions (with 0.10% fluocinonide enhancers are present in ratio to the total of the penetration and no penetration enhancers, as defined below, were enhancers, and solvents and emulsifiers of at least about included) were also tested for their vasoconstrictor scores in 0.70, preferably at least 0.85 and most preferably 0.90 or the same manner. Therefore, the ratios of a:(a+b) are Zero. 0.95. Optionally, one or more inactive ingredients may also The vasoconstrictor scores are 60.00 and 59.00, which are 35 significantly lower than the present invention’s embodi be combined with the corticosteroid. ments’ vasoconstrictor scores. As indicated above, this invention is broadly applicable to Additionally, several other control compositions were corticosteroids in general, and fluorinated corticosteroids in tested for their vasoconstrictor scores (“vasoscores'). These particular, most preferably fluocinonide or fluocinolone compositions comprised 0.10% fluocinonide, and no diiso acetonide. The following examples show its application to 40 propyl adipate, propylene glycol or dimethyl isosorbide. preparations of fluocinonide, a commonly used fluorinated Their vasoscores were 49.00, 47.00 and 44.00. corticosteroid. Fluocinonide is a corticosteroid which is the The experiments also included several Class 1 composi 21- ester of fluocinolone acetonide with the chemical name pregna-1,4-diene-320-dione.21-(acetyloxy)-6.9-dif tions as comparison points. Psorcon R ointment by Dermik luoro-11-hydroxy-16, 17-(1-methylethylidene)bis(oxy)- Laboratories, Inc. of Collegeville, Pa. with 0.05% diflo 45 rasone diacetate had a vasoscore of 101. UltravateR oint (6C, 11B, 16C.)-. Compositions containing 0.05% (all per ment by Westwood-Squibb of Evansville, Ind. with 0.05% centages are weight percentages) fluocinonide are halobetasol propionate had a vasoscore of 97, while Ultra commonly classified as Class 2. vateR cream by Westwood-Squibb with 0.05% halobetasol propionate had a vasoscore of 92. EXAMPLE 1. 50 In the ratio of (a): (a+b), penetration enhancers include at least two of propylene glycol, diisopropyl adipate, dimethyl Experiments were conducted with embodiments of the isosorbide, 1.2.6 hexanetriol, and benzyl alcohol (collec present invention and several control compositions. Com tively referred to as “a”). The solvents and emulsifiers for the positions were prepared and the investigator was blinded corticosteroid include one or more of dehydrated alcohol, with respect to the compositions. Thirty-six healthy volun 55 alcohol (95% V/v) USP 3-Cyclohexene-1-Methanol, teers were enrolled for two-day trials. On day 1, a single OC4-Dimethyl-a-(4-Methyl-3-Pentenyl)-, Steareth-2, Ste application of approximately 10 milligrams of at least eight areth-21, citric acid, CPE-215, diisopropanolamine (1:9), compositions was made to 1 cm sites on the lower aspect of DIPA/PG (1:9), ethoxydiglycol, Potassium hydroxide each volunteers forearms in accordance with a computer (10%), PEG-40 Stearate, PEG-7000, Polysorbate 60, potas generated randomization code. After applying the composi 60 sium hydroxide (1%), propylene carbonate USP propyleth tions, the sites were protected using a raised perforated ylene glycol 4, oleyl alcohol, Sodium lauryl Sulfate, Sorbitan guard. The guard was secured to the arm with a non monostearate, Sorbitan Stearate, and 1.2.3-Propanetriol Ester occlusive tape and the subjects were scheduled to return the (collectively referred to as “b'). following day after being instructed to keep the sites dry. The compositions optionally comprise non-solvent/emul After approximately 16 hours of contact with the skin, the 65 sifier ingredients, such as Glyceryl Stearate (and) PEG-100 protective guards were removed and the compositions were Stearate, carbopol 980, cyclomethicone NF, glyceryl removed from the test sites by gently washing with mild monostearate, hydroxyethyl cellulose, hydroxypropyl cellu US 7,217,422 B2 7 8 lose, isopropyl myristate, methyl paraben NF, mineral oil, What is claimed is: oleic acid NF, PEG-100 Stearate, petrolatum, propyl paraben 1. A method for enhancing potency of corticosteroids, NF, purified water, stearyl alcohol, white petrolatum, and comprising: white wax. Combining one or more corticosteroids with two or more The combination of penetration enhancers used in the penetration enhancers, and one or more of the group invention have a remarkable and unexpected result. Com consisting of solvents and emulsifiers, wherein the pounds using similar concentrations of a single penetration penetration enhancers are present in a ratio to a total of enhancer (e.g. propylene glycol as the sole penetration penetration enhancers, and solvents and emulsifiers of enhancer with 0.10% fluocinonide yielded vasoscores of at least about 0.90, and wherein the penetration enhanc 72.00, and 50.00, depending on the solvents, emulsifiers and 10 ers comprises two or more of the group consisting of non-solvent/emulsifier ingredients used) do not have simi propylene glycol, diisopropyl adipate, dimethyl isosor larly high Vaso scores. Compositions with the combination bide 1.2.6 hexanetriol, and benzyl alcohol. of penetration enhancers and formula scores of less than 2. A method for enhancing potency of corticosteroids, 0.65 also have low vaso scores. Therefore the invention comprising: results in an unexpected increase in potency of the fluoci 15 Combining one or more corticosteroids with two or more nonide. penetration enhancers, and one or more of the group consisting of solvents and emulsifiers, wherein the EXAMPLE 2 penetration enhancers are present in a ratio to a total of penetration enhancers, and solvent and emulsifiers of at One embodiment of the present invention is detailed in least about 0.90, and wherein the penetration enhancers the chart below. comprises two or more of the group consisting of TABLE 3 propylene glycol, diisopropyl adipate and dimethyl isosorbide. Component % Wiw % Wiw 3. A method for enhancing potency of corticosteroids, 25 comprising: Fluocinonide Micronized, O.1 O.1 USP Combining one or more corticosteroids with two or more Propylene Glycol, USP 70.O 74.9 penetration enhancers, and one or more of the group Dimethyl isosorbide 1S.O consisting of solvents and emulsifiers, wherein the Diisopropyl Adipate 3.0 penetration enhancers are present in a ratio to a total of Isopropyl Myristate, NF S.O 30 1.2.6 Trihydroxyhexane 2.5 penetration enhancers, and solvent and emulsifiers of at Carbopol. 980 1.2 1.O least about 0.90, and wherein one penetration enhancer Diisopropanolamine 85%: 1.2 1.O comprises propylene glycol. propylene glycol (1:9) Citric Acid, USP O.O1 O.O1 4. The method of claim 1, wherein the corticosteroid Purified Water, USP 2.49 2.49 comprises a fluorinated corticosteroid. Glyceryl monostearate 2.5 2.5 35 5. The method of claim 1, wherein the corticosteroid Glyceryl monostearate & 7.5 7.5 comprises fluocinonide. PEG Stearate 6. The method of claim 1, wherein the corticosteroid comprises fluocinolone acetonide. 7. The method of claim 4, 5, 6, or 1 wherein the corti EXAMPLE 3 40 costeroid is present at about 0.10%. Another embodiment of the present invention is detailed 8. The method of claim 4, 5, 6, or 1 wherein the corti in the chart below. costeroid is present at at least about 0.50%. 9. The method of claim 4, 5, 6, or 1 wherein the corti TABLE 4 45 costeroid is present at at least about 0.25%. 10. The method of claim 1, 2, 3, wherein the ratio is at Component % Wiw % Wiw least about 0.95. Fluocinonide Micronized, O.1 O.1 11. The method of claim 1, 2, or 3, wherein the solvents USP and emulsifiers comprise one or more of the group consist Propylene Glycol, USP 66.8 69.9 50 ing of dehydrated alcohol, alcohol (95% V/v) USP 3-Cy Dimethyl isosorbide S.O clohexene-l-Methanol, OC4-Dimethyl-a-(4-Methyl-3-Pente Diisopropyl Adipate 2.0 Isopropyl Myristate, NF S.O S.O nyl)-, Steareth-2, Steareth-21, citric acid, CPE-215, Carbopol. 980 O.S O.S diisopropanolamine (1:9), DIPA/PG (1:9), ethoxydiglycol, Diisopropanolamine 85%: O.S O.S Potassium hydroxide (10%), PEG-40 Stearate, PEG-7000, propylene glycol (1:9) Polysorbate 60, potassium hydroxide (1%), propylene car White Petrolatum, USP S.O S.O 55 Glyceryl monostearate 6.O 6.O bonate USP propylethylene glycol 4, oleyl alcohol, sodium PEG 100 Stearate 6.O 6.O lauryl Sulfate, Sorbitan monoStearate, Sorbitan Stearate, and Stearyl alcohol, NF S.O S.O 1,2,3-Propanetriyl Ester. Sodium Lauryl Sulfate, NF O.1 12. The method of claim 1, 2, or 3, wherein the compo 60 sition further comprises one or more non-solvent/emulsifier It is to be understood that while the invention has been ingredients. described in conjunction with the detailed description 13. The method of claim 12 wherein the non-solvent/ thereof, that the foregoing description is intended to illus emulsifier ingredients comprise one or more of the group trate and not limit the scope of the invention, which is consisting of Glyceryl Stearate (and) PEG-100 Stearate, defined by the scope of the appended claims. Other aspects, 65 carbopol 980, cyclomethicone NF, glyceryl monostearate, advantages, and modifications are evident from a review of hydroxyethyl cellulose, hydroxypropyl cellulose, isopropyl the following claims. myristate, methyl paraben NF, mineral oil, oleic acid NF, US 7,217,422 B2 9 10 PEG-100 Stearate, petrolatum, propyl paraben NF, purified 16. The method of claim 13 wherein the non-solvent/ water, Stearyl alcohol, white petrolatum, and white wax. emulsifier ingredients are present at about 11% to about 14. The method of claim 1, 2, or 3, wherein the solvents 27%. and emulsifiers are present at about 4–5%. 15. The method of claim 13 wherein the non-solvent? 5 emulsifier ingredients are present at about 11% to about 53%. k . . . .