United States Patent [19]
`Liu et al.
`
`111111111111111111111111111111111111111111111111111111111111111111111111111
`US005456851A
`[11] Patent Number:
`[45] Date of Patent:
`
`5,456,851
`Oct. 10, 1995
`
`[54] KETOCONAZOLE SHAMPOO CONTAINING
`BUTYLATED HYDROXYTOLUENE OR
`BUTYLATED HYDROXYANISOLE
`
`[75]
`
`Inventors: Jue-Chen Liu, Neshanick; Jonas C. T.
`Wang, Robbinsville; Mohammed
`Yusuf, Edison, all of N.J.
`
`[73] Assignee: Johnson & Johnson Consumer
`Products, Inc., Skillman, N.J.
`
`[21] Appl. No.: 224,382
`
`[22] Filed:
`
`Apr. 7, 1994
`
`Int. Cl.6
`........................................................ C11D 3/48
`[51]
`[52] U.S. Cl . .................... 2521106; 252/173; 252/174.11;
`252/174.23; 252/544; 252/547; 252/551;
`252/555; 252/399; 252/DIG. 13; 514/852;
`514/881
`[58] Field of Search .................................... 252/89.1, 106,
`252/542, 544, 547, 550, 551, 555, DIG. 13,
`174.11, 174.23, 399; 514/852, 881
`
`[56]
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`8/1986 Jacquet et al ........................... 514/844
`4,608,392
`5,061,700 10/1991 Dow et al ............................... 514/169
`5,310,545
`5/1994 Eisen ......................................... 424/49
`
`FOREIGN PATENT DOCUMENTS
`
`OTHER PUBLICATIONS
`
`Berger et al., "Double-Blind Placeb(}--Controlled Trial of
`Ketoconazole 2% Shampoo in the Treatment of Moderat to
`Severe Dandruff', Adv. Ther., 7(5), Sep./Oct. 1990, pp.
`247-256.
`Go et al., "A Double-Blind Trial of 1% Ketoconazole
`Shampoo Versus Placebo in the Treatment of Dandruff',
`Mycoses, 35(3-4), 1992, pp. 103-105.
`Danby
`et
`al.,
`"A Randomized Double-Blind,
`Placeb(}--Controlled Trial of Ketoconazole 2% Shampoo
`Versus Selenium Sulfide 2.5% Shampoo ... ", Journal of the
`American Academy of Dermatology, 29(6), Dec. 1993, pp.
`1008-1012.
`
`Primary Examiner-Paul Lieberman
`Assistant Examiner-Lama M. Douyon
`Attorney, Agent, or Firm-Charles J. Metz
`
`[57]
`
`ABSTRACT
`
`A shampoo that contains ketoconazole, a surfactant, a foam(cid:173)
`ing agent, thickener sufficient to give the final formulation a
`viscosity in the range of about 4,000 to about 9,000 cps at
`room temperature (i.e., about 20°-25° C.), preservative,
`butylated hydroxytoluene or butylated hydroxyanisole in an
`amount sufficient to retard degradation of the ketoconazole,
`and acid, base or buffer sufficient to give the final compo(cid:173)
`sition a pH in the range of from about 4 to about 10.
`
`W092/00057
`
`1/1992 WIPO.
`
`14 Claims, No Drawings
`
`1
`
`

`

`1
`KETOCONAZOLE SHAMPOO CONTAINING
`BUTYLATED HYDROXYTOLUENE OR
`BUTYLATED HYDROXYANISOLE
`
`2
`base or buffer sufficient to give the final composition a pH
`in the range of from about 4 to about 10, preferably from
`about 6.5 to about 8, and more preferably from 6.9 to 7.4.
`
`5,456,851
`
`The invention relates to a ketoconazole-containing sham-
`poo having improved stability.
`
`BACKGROUND OF THE INVENTION
`
`Ketoconazole is the generic name for the compound
`(±)-cis-1-acety l-4-[ 4-[[2-(2,4-dichlorophenyl)-2-(1H-imi(cid:173)
`dazol-1-ylmethy 1)-1 ,3-dioxolan-4-y l ]methoxy ]phenyl ]pip(cid:173)
`erazine, having the formula:
`
`5
`
`THE PRIOR ART
`
`Butylated hydroxytoluene, whose proper chemical name
`is 2,6-bis (1,1-dimethylethyl)-4-methylphenol, also 2,6-di(cid:173)
`tert-butyl-p-cresol or 2,6-di-tert-butyl-4-methylphenol, is
`10 marketed as an antioxidant for food, animal feed, petroleum
`products, synthetic rubbers, plastics, animal and vegetable
`oils, and soaps, and as an antiskinning agent in paints and
`inks. (Ref. -Page 238 of the Merck Index, Eleventh Edition.)
`Butylated hydroxyanisole, whose proper chemical name
`is 2(3)-tert-butyl-4-methoxyphenol, is marketed as an anti(cid:173)
`oxidant, especially for food. (Ref.- Page 1547 of the Merck
`Index, Eleventh Edition.)
`
`15
`
`20
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`
`Ketoconazole was originally described by Heeres et al.,
`for instance, in U.S. Pat. No. 4,335,125, in which its
`principal utility was as an antifungal compound. Ketocona(cid:173)
`zole was also disclosed by Rosenberg et al. in U.S. Pat. No.
`4,569,935 to be useful in the topical treatment of psoriasis
`and seborrheic dermatitis. Pursuant to this utility, ketocona(cid:173)
`zole has been marketed in a 2% shampoo formulation
`(available in the United States by prescription only) for the
`treatment of scaling due to dandruff. The components of this
`shampoo include coconut fatty acid diethanolamide, diso(cid:173)
`dium monolaury1 ether sulphosuccinate, colorant such as
`F.D. & C. Red No. 40, hydrochloric acid and/or sodium
`hydroxide to control pH, imidurea, laurdimonium hydro(cid:173)
`lyzed animal collagen, macrogol 120 methyl glucose
`dioleate, perfume bouquet, purified water, sodium Iaury!
`ether sulphate, and ketoconazole (2% ).
`Although the above-described shampoo is efficacious for
`dandruff treatment, it was desired to improve its cosmetic
`attributes such as lathering and conditioning, and to develop 45
`an efficacious formulation that, if desired, could contain less
`than 2% ketoconazole. However, since ketoconazole is
`subject to slow degradation by oxidation and hydrolysis, any
`formulation that contains significantly less than 2% keto(cid:173)
`conazole must be effectively stabilized in order to have an 50
`acceptable shelf life. The present invention is based on the
`discovery of a formulation for a ketoconazole-containing
`shampoo that exhibits excellent cosmetic attributes such as
`lathering and conditioning, and is acceptably stable to deg(cid:173)
`radation so that, if desired, the shampoo can be formulated 55
`to contain less than 2% ketoconazole.
`
`The shampoo of the invention contains ketoconazole, at
`least one surfactant, a foaming agent, thickeners sufficient to
`give the final formulation a viscosity in the range of about
`25 4,000 to about 9,000 cps at room temperature, preservatives
`including butylated hydroxytoluene sufficient to prevent
`degradation of the final composition, and acid, base or buffer
`sufficient to give the final composition a pH in the range of
`from about 4 to about 10. Each class of ingredients will be
`30 discussed in tum.
`Ketoconazole is employed in the shampoo in an amount
`effective to combat scaling due to dandruff. An effective
`amount will usually be found within the range offrom about
`0.3 weight percent up to about 3 weight percent, based on
`35 weight of the entire shampoo formulation. Preferred
`amounts are usually found within the range of from about
`0.8 to 2 weight percent, and more preferably from about 0.9
`to about 1.1 weight percent. At concentrations below the
`indicated range, the effectiveness begins to diminish to
`40 unacceptable levels, and at concentrations higher than about
`3 weight percent, the limited solubility of ketoconazole in
`aqueous media, even with surfactants present, becomes a
`significant factor.
`The shampoo of the invention contains one or more
`surfactants, which are employed principally as cleansing
`agents. Specific illustrations of surfactants that have been
`found to be useful include the following compositions:
`Sodium laureth sulfate, a composition having the formula
`CH3(CH2) 10CHiOCH2CH2)nOS03Na, wherein n repre(cid:173)
`sents a number having an average value of from 1 to 4; and
`Sodium cocoyl sarcosinate, which is the sodium salt of
`cocoyl sarcosine. Cocoyl sarcosine is the coconut oil fatty
`acid amide of sarcosine (N-methylglycine or methylamino(cid:173)
`ethanoic acid). Coconut fatty acid is a mixture of myristic
`acid, lauric acid, palmitic acid and stearic acid.
`Other surfactants that can be employed in the shampoo of
`the invention include sodium cl4-16 olefin sulfonates,
`sodium Iaury! sulfate, cocamidopropylamine oxide, laura-
`60 mido DEA (lauramido diethanolamine), cocamidopropyl
`betaine, disodium oleamido MIPA sulfosuccinate, disodium
`cocamido MIPA sulfosuccinate, disodium laureth su1fosuc(cid:173)
`cinate, cocoamphocarboxy-glycinate, and disodium olea(cid:173)
`mido MEA sulfosuccinate. These surfactants are all known
`in the shampoo and cosmetic arts.
`The shampoo of the invention also contains foaming
`agents such as fatty acid mono- and di-alkanolamides, for
`
`65
`
`BRIEF SUMMARY OF THE INVENTION
`
`The present invention provides an aqueous shampoo that
`contains ketoconazo1e, a surfactant, a foaming agent, thick(cid:173)
`ener sufficient to give the final formulation a viscosity in the
`range of about 4,000 to about 9,000 cps at room temperature
`(i.e., about 20°-25° C.), preservative, an antioxidant
`selected from the group consisting of butylated hydroxy(cid:173)
`toluene and butylated hydroxy anisole in an amount suffi(cid:173)
`cient to retard degradation of the ketoconazole, and acid,
`
`2
`
`

`

`3
`instance, cocamide MEA (a mixture of coconut acid mono(cid:173)
`the
`ethanolamides of
`formula R-CO-NHCH2CH20H
`wherein R represents the residue after removal of the car(cid:173)
`boxyl group of coconut fatty acid), cocamide DEA [a
`formula R-CO(cid:173)
`mixture of diethanolamides of the
`N(CH2CH20H)z wherein R is as defined above], oleamide
`MEA and oleamide DEA.
`The shampoo of the invention contains a thickener to
`impart a viscosity to the formulation in the range of from
`about 4,000 to about 9,000 cps at room temperature. Such 10
`thickeners include Carbopol 1342, which is a copolymer of
`C10. 30alkyl acrylates, acrylic acid and/or methacrylic acid,
`cross-linked with an allyl ether of sucrose. Other thickeners
`that can be used include cellulose derivatives such as
`hydroxypropyl methylcellulose, hydroxyethyl cellulose, car-
`boxymethyl cellulose, and the like. The addition of a small
`amount of salt (NaCI) also serves to control the viscosity of
`the final formulation. Usually, the amount of salt added will
`be within the range of from about 0.2S to 0.6 weight percent.
`The preservatives that can be used in the shampoo of the
`2
`invention include tetrasodium EDTA (the tetrasodium salt of 0
`ethylenediamine tetraacetic acid-used as a chelating agent to
`protect against degradation caused by metal ions and also to
`enhance anti-bacterial activity) and quatemium-lS [1-(3-
`chloroallyl)-3,S, 7-triaza-1-aziona-adamantane chloride
`-
`used as an antimicrobial agent]. Other preservatives that can
`be used include paraben, Kathon CG biocide (a mixture of
`S-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-
`isothiazolin-3-one), phenoxyethanol, benzyl alcohol, and
`the like.
`An important feature of the present invention is the
`discovery that a carefully controlled amount of an antioxi(cid:173)
`dant selected from the group consisting of butylated
`hydroxytoluene ("BHT') and butylated hydroxyanisole
`("BHA") is effective to stabilize the ketoconazole present in
`the shampoo against degradation during accelerated aging
`for 13 weeks at sao C., which is considered to be predictive
`of performance during storage at ambient temperatures for
`two years. Effective stability is considered to be a loss of
`active ingredient (in this case, ketoconazole) during storage
`of not more than about 10 percent. The proportion of BHT
`or BHA that has been found to be most effective is within the
`range of from about 0.01 to about 1, and preferably
`0.1±0.02S, weight percent, based on weight of the entire
`shampoo formulation (See Table 1, below). Surprisingly,
`proportions greater than this amount do not stabilize as
`effectively for the 13-week accelerated aging period,
`although if one extends the accelerated aging period longer
`than 13 weeks, greater proportions of BHT or BHA tend to
`be more effective, since the BHT or BHA itself is also
`subject to degradation (see Table 2, below). However, it is
`well recognized by government regulatory agencies and in
`the pharmaceutical and cosmetic industries that stability
`testing for 13 weeks at sao c. is quite sufficient to predict
`product stability during normal shelf life storage for two (2)
`years at room temperature. It is also equally important that,
`for safety reasons (that is, to minimize the potential for skin
`sensitization), it is desired to use as small an amount as
`possible of BHT or BHA.
`The shampoo of the invention can contain other materials 60
`such as fragrances, colorants, opacifiers, conditioners such
`as polyquaternium-7 [the polymeric quaternary ammonium
`salt of acrylamide and dimethyl diallyl ammonium chlo(cid:173)
`ride], pearlizing agents such as ethylene glycol distearate
`and ethylene glycol monostearate, etc., that are standard in 65
`shampoo formulations.
`The shampoo contains acids, bases, and buffers, as needed
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`5,456,851
`
`4
`to maintain a pH of from 4 to 10, and preferably from about
`6.S to 8, and more preferably from 6.9 to 7.4. (A neutral pH
`is desired in order to minimize the potential for skin sensi(cid:173)
`tization.) The nature and mode of use of such materials are
`5 known in the art.
`The components of the shampoo are employed in con-
`ventional amounts, for example:
`(a) 36% to 4S% surfactants,
`(b) 2% to 6% foaming agent,
`(c) 0.3% to 3% ketoconazole,
`(d) 0.2% to 1.3% thickener,
`(e) 0.01% to 1% BHT or BHA;
`(f) preservatives sufficient to retard degradation of the
`final composition in order to give adequate shelf life,
`(g) acid, base or buffer to yield a pH in the desired range,
`and
`(h) water QS ad 100% (that is, sufficient water to make
`100%).
`
`15
`
`Standard Preparation of Shampoo
`
`A vessel was charged with a 1.64% stock solution of
`Carbopol 1342 (prepared using a Quadro disperser which
`functions by keeping the powdered polymer evenly divided
`and pulling the powder by a vacuum into a stream of water)
`and deionized water, and heated to about 70° C. Both
`surfactants, i.e. sodium laureth sulfate and sodium cocoyl
`sarcosinate, were added, followed by the foaming agent,
`cocamide MEA, and a pearlizing agent (ethylene glycol
`distearate) and mixed until complete dissolution. Then the
`BHT was added and the mixture was stirred until complete
`dissolution thereof. The solution was allowed to cool
`slightly, whereupon the antifungal ingredient ketoconazole
`was added while stirring well. (The ketoconazole is added
`while the pH is slightly acidic, to facilitate dissolution.) The
`mixture was allowed to cool to about 40° C., at which
`temperature there were added the conditioner (polyquater(cid:173)
`nium-7), the preservatives quaternium-lS and tetrasodium
`EDTA, the colorants and fragrances, and the NaCI for
`thickening the solution. The pH of the solution was adjusted
`to 6.9-7.4 with a 2S% aq. solution of NaOH and deionized
`water was added to the final volume.
`Using the general procedure described above, the follow(cid:173)
`ing shampoo formulations were made:
`
`EXAMPLE 1:
`
`Shampoo Formulations for Normal Hair
`
`Ingredients
`
`sodium 1aureth sulfate
`sodium cocoy1 sarcosinate
`cocamide MEA
`ketoconazole USP
`glycol distearate
`polyquaternium· 7
`Carbopol 1342
`tetrasodium EDTA
`perfume oil
`sodium chloride
`sodium hydroxide 25%
`butylated hydroxytoluene
`quaternium-15
`colorants
`
`(a)
`
`30
`10
`4
`1
`1.25
`I
`0.6
`0.5
`0.5
`0.3
`0.92
`0.1
`0.05
`0.001
`
`(b)
`
`30
`10
`4
`2
`1.25
`1
`0.6
`0.5
`0.5
`0.3
`0.9
`0.1
`0.05
`0.001
`
`3
`
`

`

`5,456,851
`
`5
`
`-continued
`
`6
`remaining for each sample after the indicated number of
`weeks:
`
`Ingredients
`
`deionized water QS ad
`
`(a)
`
`100
`
`(b)
`
`100
`
`5
`
`TABLE 1
`
`Percent of original proportion of ketoconazole remaining
`Stability analyses at 50° C. for the 24 weeks is
`indicated as follows
`
`Week
`
`10
`
`15
`
`0
`4
`8
`12
`16
`20
`24
`
`0.0% 1
`
`100
`97.98
`97.18
`85.61
`88.49
`82.22
`82.12
`
`0.01%
`
`0.1%
`
`0.4%
`
`0.7%
`
`1.0%
`
`100
`99.01
`97.75
`92.30
`88.80
`84.75
`84.13
`
`100
`10L12
`98.84
`99.48
`95.93
`87.17
`86.44
`
`100
`102.00
`101.07
`96.35
`93.01
`90.29
`89.46
`
`100
`101.23
`100.78
`94.49
`93.24
`89.91
`92.82
`
`100
`101.89
`102.77
`95.91
`93.27
`93.27
`90.68
`
`1 Percent BHT in original sample.
`Note - the relative standard deviation for all but two samples was less than
`2%.
`The samples were also analyzed for BHT content after
`20 storage for 24 weeks at 4° C. and at 50° C. The results are
`displayed in the following table:
`
`25
`
`TABLE 2
`
`BHT analysis
`
`FORMULATED % BHT
`
`4° C. 24 wks.
`% BHT
`
`50° C. 24 wks.
`%BHT
`
`1.0%
`0.7%
`30 0.4%
`0.1%
`0.01%
`0.0%
`PLACEB02
`
`0.940%
`0.583%
`0.352%
`0.084%
`0.009%
`0
`0.0968%
`
`0.277%
`0.218%
`0.107%
`0.023%
`0.005
`0
`0.0631%
`
`35
`
`EXAMPLE2:
`
`Shampoo Formulations for Oily Hair
`
`Ingredients
`
`(a)
`
`(b)
`
`(c)
`
`sodium laureth sulfate
`sodium cocoyl sarcosinate
`cocarnide MEA
`ketoconazole USP
`glycol distearate
`polyquaternium-7
`Carbopol 1342
`tetrasodium EDTA
`perfume oil
`sodium chloride
`sodium hydroxide 25%
`butylated hydroxytoluene
`quaternium-15
`colorants
`deionized water QS ad
`
`33.33
`11
`4
`I
`1.25
`0.6
`0.75
`0.5
`0.5
`0.3
`L18
`0.1
`0.05
`0.0053
`100
`
`33.33
`11
`4
`1
`1.25
`0.6
`0.75
`0.5
`0.5
`0.3
`1.243
`0.1
`0.05
`0.0053
`100
`
`33.33
`11
`4
`2
`1.25
`0.6
`0.75
`0.5
`0.5
`0.3
`L18
`0.1
`0.05
`0.0053
`100
`
`EXAMPLE 3:
`
`Shampoo Formulations for Dry or Damaged Hair
`
`Ingredients
`
`(a)
`
`(b)
`
`(c)
`
`sodium 1aureth sulfate
`sodium cocoy1 sarcosinate
`cocarnide MEA
`ketoconazole USP
`glycol distearate
`po1yquaternium-7
`Carbopol 1342
`tetrasodium EDTA
`perfume oil
`sodium chloride
`sodium hydroxide 25%
`butylated hydroxytoluene
`quaternium-15
`colorants
`deionized water QS ad
`
`30
`10
`4
`1
`1.25
`5
`0.5
`0.5
`0.5
`0.4
`0.7333
`0.1
`0.05
`0.0018
`100
`
`30
`10
`4
`1
`1.25
`5
`0.5
`0.5
`0.5
`0.4
`0.733
`0.1
`0.05
`0.0018
`100
`
`30
`10
`4
`2
`1.25
`5
`0.5
`0.5
`0.5
`0.3
`L19
`0.1
`0.05
`0.0018
`100
`
`2 Contained 0.1% BHT and no ketoconozole.
`What is claimed is:
`1. An aqueous shampoo that contains ketoconazole in an
`amount within the range of from about 0.3 weight percent to
`about 3 weight percent, based on weight of the shampoo, to
`40 combat scaling due to dandruff, a surfactant, a foaming
`agent, thickener sufficient to give the final formulation a
`viscosity in the range of about 4,000 to about 9,000 cps at
`room temperature, an antioxidant in an amount from 0.01 to
`1 weight percent selected from the group consisting of
`45 butylated hydroxytoluene and butylated hydroxyanisole to
`retard degradation of the ketoconazole, acid, base or buffer
`sufficient to give the shampoo a pH in the range of from
`about 4 to about 10 and preservative sufficient to retard
`degradation of the final composition.
`2. The shampoo of claim 1 wherein the pH is in the range
`of from about 6.5 to about 8.
`3. The shampoo of claim 2 wherein the pH is in the range
`of from about 6.9 to 7.4.
`4. The shampoo of claim 1, 2 or 3 wherein the antioxidant
`is butylated hydroxytoluene employed in an amount of
`0.1±0.025 weight percent, based on weight of the shampoo.
`5. The shampoo of claim 1 wherein the ketoconazole is
`employed in an amount within the range of from about 0.8
`weight percent to about 2.0 weight percent, based on weight
`60 of the shampoo.
`6. The shampoo of claim 5 wherein the ketoconazole is
`employed in an amount within the range of from about 0.9
`weight percent to about 1.1 weight percent, based on weight
`of the shampoo.
`7. A shampoo according to claim 1 comprising one or
`more surfactants selected from the group consisting of
`sodium C 14_16 olefin sulfonates, sodium lauryl sulfate,
`
`In all the formulations given above in Examples 1-3, the 50
`proportion of sodium hydroxide may vary slightly, to arrive
`at the more preferred pH level of 6.9 to 7.4, and the
`proportion of salt (NaCl) may vary, to arrive at the desired
`viscosity.
`
`55
`
`EXAMPLE4:
`
`Stability Studies
`
`The formulation described above as Example 1 (a)
`[Shampoo formulation for normal hair containing 1% keto(cid:173)
`conazole]was subjected to stability studies, as follows:
`Shampoo formulations containing 0, 0.01, 0.1, 0.4, 0. 7
`and 1.0 weight % BHT were stored at 50° C. for 24 weeks.
`At 0, 4, 8, 12, 16, 20 and 24 weeks, samples were taken from 65
`each formulation and analyzed for ketoconazole content.
`The table below reports the percentage of ketoconazole
`
`4
`
`

`

`5,456,851
`
`7
`sodium laureth sulfate, cocamidopropylamine oxide, laura(cid:173)
`mido diethanolamine, cocamidopropyl betaine, sodium
`cocoyl sarcosinate, disodium oleamido monoisopropanola(cid:173)
`mine sulfosuccinate, disodium cocamido monoisopropano(cid:173)
`lamine sulfosuccinate, disodium laureth sulfosuccinate, 5
`cocoamphocarboxy-glycinate, disodium oleamido monoet(cid:173)
`hanolamine sulfosuccinate.
`8. A shampoo according to claim 1 wherein the foaming
`agent is selected from the group of fatty acid mono- and
`di-alkanolamides consisting of cocamide monoethanola- 10
`mine, cocamide diethanolamine, oleamide monoethanola(cid:173)
`mine and oleamide diethanolamine.
`9. A shampoo according to claim 1 that additionally
`contains polyquaternium-7 as a conditioner.
`10. A shampoo according to claim 1 further comprising 15
`one or more pearlizing agents selected from the group
`consisting of ethylene glycol distearate and ethylene glycol
`monostearate.
`11. A shampoo according to claim 1 further comprising
`one or more fragrances and one or more colorants.
`12. A shampoo according to claim 1 comprising by weight
`based on the total weight of the formulation approximately:
`(a) 36% to 45% surfactants,
`(b) 2% to 6% foaming agent,
`(c) 0.3% to 3% ketoconazole,
`(d) 0.2% to 1.3% thickener,
`(e) 0.1% to 1% butylated hydroxytoluene antioxidant;
`(f) preservatives sufficient to retard degradation of the
`final composition,
`(g) acid, base or buffer to yield a pH in the range of from
`6.9 to 7.4, and
`(h) water QS ad 100%.
`13. A shampoo according to claim 12 comprising by
`weight based on the total weight of the formulation approxi(cid:173)
`mately:
`(a) 36% to 45% surfactants,
`(b) 2% to 6% foaming agent,
`(c) 0.3% to 3% ketoconazole,
`(d) 0.4% to 8% conditioner,
`
`25
`
`30
`
`8
`(e) 0.2% to 1.3% thickener,
`(f) 1% to 1.5% pearlizing agent,
`(g) 0.5% to 1% preservative(s),
`(h) 0.1±0.025% butylated hydroxtoluene antioxidant,
`(i) acid, base or buffer to yield a pH in the range of 6.9 to
`7.4,
`G) fragrance(s) and colorant(s), and
`(k) water QS ad 100%.
`14. A process of preparing a shampoo formulation that
`contains ketocanazole in an amount within the range of from
`about 0.3 weight percent to about 3 weight percent, based on
`weight of the shampoo to combat scaling due to dandruff, a
`surfactant, a foaming agent, thickener sufficient to give the
`final formulation a viscosity in the range of about 4,000 to
`about 9,000 cps at room temperature, an antioxidant in an
`amount from 0.01 to 1 weight percent selected from the
`group consisting ofbutylated hydroxytoluene and butylated
`20 hydroxyanisole to retard degradation of the detoconazole,
`acid, base or buffer sufficient to give the shampoo a pH in the
`range of from about4 to about 10, and preservative sufficient
`to retard degradation of the final composition, said process
`comprising the steps of:
`(a) heating a solution of thickener and deionized water,
`(b) mixing the surfactants, the foaming agent and option(cid:173)
`ally the pearlizing agent with the solution of (a),
`(c) mixing the butylated hydroxytoluene or butylated
`hydroxyanisole with the solution of (b),
`(d) mixing the antifungal ketoconazole with the solution
`of (c),
`(e) allowing the solution of (d) to cool somewhat and
`mixing therewith the preservative(s) and the sodium
`chloride for thickening, and optionally the conditioner,
`the fragrance(s) and colorant(s),
`(f) adding acid, base or buffer to the solution of (e) to yield
`a pH in the range of 4 to 10, and
`(g) adding deionized water to the solution of (f) to 100%.
`
`35
`
`40
`
`* * * * *
`
`5
`
`