WO2008057411A1

WO2008057411A1 - Kits containing benzoyl peroxide pads and another acne-treating composition, and formulations and methods of use therefor

Info

Publication number: WO2008057411A1
Application number: PCT/US2007/023134
Authority: WO
Inventors: Karl F. Popp; James Peter Hartman
Original assignee: Stiefel Laboratories, Inc.
Priority date: 2006-11-02
Filing date: 2007-11-02
Publication date: 2008-05-15

Abstract

A kit including a first product including at least one pad containing a benzoyl peroxide composition absorbed thereon and a second product including a container containing a flowable composition of one or more agents suitable for the treatment of acne, is provided. Also provided is a method for treating acne by administering to a patient in need thereof a combination of products including a first product including at least one pad containing a benzoyl peroxide composition absorbed thereon, and a second product including a container containing a flowable composition of one or more agents suitable for the treatment of acne.

Description

KITS CONTAINING BENZOYL PEROXIDE PADS AND ANOTHER ACNE- TREATING COMPOSITION. AND FORMULATIONS AND METHODS OF USE

THEREFOR

FIELD OF THE INVENTION

[oi] The present subject matter relates generally to a kit comprising at least one benzoyl peroxide pad and a container containing a flowable composition of one or more agents suitable for the treatment of acne, formulations thereof, and methods of using the same to treat various skin disorders.

BACKGROUND OF THE INVENTION

[02] Acne is a condition of the human skin characterized by an excess flow of sebum, or skin oil, from the sebaceous glands located in the pilosebaceous apparatus. Sebum reaches the skin surface through the duct of the hair follicle. The presence of excessive amounts of sebum in the duct and on the skin acts to block or stagnate the continuous flow of sebum from the follicular duct, thus producing a thickening and a solidification of the sebum to form a solid plug known as a comedone. When this process occurs, hyperkeratinization of the follicular opening is stimulated, thus completely closing the duct. The usual results are papules, pustules, or cysts, often contaminated with bacteria which cause secondary infections. Acne is particularly characterized by the presence of comedones, inflammatory papules, pustules, or cysts. The effect of acne ranges from slight skin irritation and pitting to disfiguring scars.

[03] Many topical therapeutic agents are employed in the treatment of acne and seborrhea to prevent the blocking of the follicular duct, to reopen the duct once it has become blocked, to act against the infecting bacteria or the thickened sebum, or to provide combinations of each of these actions. The horny outer layer of the skin, which is known as the stratum corneum, is formed of dead cells composed largely of keratin. Therapeutic agents which act to prevent the blocking of the follicular duct by promoting the removal or sloughing off of excess keratin are known as keratolytic agents.

[04] Benzoyl peroxide has been used as a very effective keratolytic and antibacterial agent in the treatment of acne. The topical application of benzoyl peroxide for skin lesion therapy is well known. For example, U.S. Patent Nos. 5,445,823, 5,545,407, and 5,932,228 disclose compositions for treating acne and other skin lesions and also to methods of treatment utilizing these compositions. These compositions and methods of treatment employ benzoyl peroxide, a compound for reducing the skin irritation associated with benzoyl peroxide, and a topical carrier.

[05] Similarly, U.S. Patent Application Publication No. 2004/0101566 discloses nanoparticulate compositions comprising benzoyl peroxide. The benzoyl peroxide particles of the composition have an effective average particle size of less than about 2 microns. The nanoparticulate benzoyl peroxide is used in methods of treating cutaneous disorders.

[06] Likewise, U.S. Patent Application Publication No. 2005/0255133 discloses a topical composition for treatment of skin disorders such as acne. The composition contains benzoyl peroxide in an amount from between 0.5% and 20% by weight. There is also provided a water miscible solvent in an amount between 10% and 95% by weight for solubilizing the benzoyl peroxide. Finally, a water miscible or water dispersible surfactant is present in an amount between 0.5% and 95% by weight. [07] In addition, U. S Patent Application Publication No. 2003/0077301 discloses a topical pharmaceutical composition for the treatment of inflammatory dermatoses, including acne vulgaris, together with a method of use of the topical composition. The composition and method involve the topical use of an active agent effective in the treatment of inflammatory dermatoses plus a permeation-enhancing base that gives the composition a pH of about 8 to about 13, preferably about 8 to about 11.5, and most preferably about 8.5 to about 10.5. The active agent can be benzoyl peroxide.

[08] Similarly, PanOxyl Bar® is a commercial product that is known for the treatment of acne. In addition to containing benzoyl peroxide, it also contains cetearyl alcohol, cocamidopropyl betaine, corn starch, glycerin, hydrogenated castor oil, lactic acid, mineral oil, optical brighteners, PEG-14M, potassium lauryl sulfate, potassium phosphate, silica, sodium lauryl sulfate, sodium sulfate, titanium dioxide and water. The consistency of PanOxyl Bar® is similar to that of bar soap. [09] Benzoyl peroxide is also found in a variety of over-the-counter and prescription acne products which take the form of lotions, creams or gels. Tubes and bottles of acne medicines are the most common ways of packaging the compositions containing the anti-acne medications, including benzoyl peroxide. However, tubes and bottles are often inconvenient for patients to carry to school, camp, office, etc. Consequently, over the last decade a new method of delivering many anti-acne agents has evolved based on incorporating active anti-acne ingredients into small cloth towelettes called wipes or pledgettes. These pledgettes can then be packaged in a sealed pouch that can be conveniently opened at the time of use. Additionally, since only one dose is opened at a time, several patients can "share" a box of such pledgettes without exposure to one another's germs, dirt, etc. [10] Topical antibiotics are another popular prescription treatment for acne.

Today, wipes or pledgettes containing topical antibiotics such as clindamycin and erythromycin are widely used for their convenience, as well as their safety and efficacy. in] Attempts to incorporate benzoyl peroxide into wipes or pledgettes have also been made. For example, U.S. Patent No. 6,740,330 discloses an article for use in the treatment of acne vulgaris comprising a cloth pledgette impregnated with a composition comprising benzoyl peroxide and an amount of acetone sufficient to solubilize the benzoyl peroxide. In a preferred embodiment, the article is packaged in an individual pouch.

[12] Meanwhile, U.S. Patent Nos. 5,242,433, 5,254,109, 5,368,581 , 5,417,674,

5,460,620, 5,470,323, and 5,562,642 all disclose a system and method for applying a plurality, preferably two, dermatological agents to the skin from a single dispensing and applicator system comprising a plurality of compartmentalized applicator pads which may be exposed and sequentially or simultaneously applied to the skin area to be treated. One pad of the acne treatment system will preferably comprise an effective amount of an organic peroxide, such as benzoyl peroxide.

[13] Additionally, U.S. Patent Nos. 5,538,732 and 6,001 ,380 disclose a method for applying a plurality of dermatological agents to the skin from a single dispensing and applicator sheet comprising a plurality of discrete areas. The discrete areas comprise at least two dermatological agents which are simultaneously released from the sheet and applied to the afflicted skin area when the sheet is rubbed over wet skin.

[14] Further, U.S. Patent Application Publication Nos. 2005/0025817,

2005/0100585, and 2005/0232978 disclose a delivery system comprising a pad and an emulsion composition thereon. The emulsion composition comprises an insoluble dermatologically active ingredient with a viscosity that permits substantially uniform absorption of the composition onto the pad. The pad is then packaged in a sealed container. Benzoyl peroxide is a preferred active ingredient in the disclosed delivery system. The benzoyl peroxide is incorporated into the emulsion composition prior to being retained by the pad.

[15] Accordingly, there remains a need in the art for topical compositions containing benzoyl peroxide for treating a dermatological disorder that are capable of treating the affected area of skin while reducing the irritation associated with the benzoyl peroxide treatment. In addition, there remains a need in the art for enhancing the efficacy of a benzoyl peroxide treatment of an area of skin afflicted with acne. The present subject matter addresses these needs.

SUMMARY OF THE INVENTION

[16] The present subject matter relates generally to a kit comprising at least one pad comprising therapeutically effective levels of benzoyl peroxide absorbed thereon and a container containing a flowable composition of one or more agents suitable for the treatment of acne, formulations thereof, and methods of using the same to treat various skin disorders.

[17] In this regard, an embodiment of the present subject matter relates to a kit comprising at least one pad containing a benzoyl peroxide composition absorbed thereon, said drug composition comprising from about 2.5% to about 13% by weight benzoyl peroxide, from about 80% to about 90% by weight water, and from about 0.1 % to about 1.5% by weight of a surfactant system; and a container containing a flowable composition of one or more agents suitable for the treatment of acne. [18] Another embodiment of the present subject matter relates to a kit wherein the kit comprises at least one additional composition.

[19] Another embodiment of the present subject matter relates to a method for treating acne comprising administering to a patient in need thereof a combination of products comprising a first product comprising at least one pad containing a drug composition absorbed thereon, said drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80-90% by weight water, and about 0.10-1.5% by weight of a surfactant system, and a second product comprising a container containing a flowable composition of one or more agents suitable for the treatment of acne.

[20] An additional embodiment of the present subject matter relates to a method further comprising administering a third product comprising a soap-free cleanser to aid in cleansing the skin. pi] Still another embodiment of the present subject matter relates to a method further comprising a final step of administering a barrier repair composition.

[22] An embodiment of the present subject matter relates to a package comprising an outer container; and a first product container and a second product container within the outer container, wherein the first product container contains at least one pad containing a drug composition absorbed thereon, the drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80-90% by weight water, and about 0.1-1.5% by weight of a surfactant system; and the second product container contains a flowable composition of one or more agents suitable for the treatment of acne. DETAILED DESCRIPTION OF THE INVENTION Definitions

[23] As used herein, "absorb", "absorbs" and "absorbed" are used interchangeably and refer to the relationship between the drug composition and the pad of the present subject matter. In particular, "absorb" refers to the drug composition being removably entrained within the pores of the pad, as well as on the surface of the pad. The drug composition is at least partially absorbed onto and into the pad. The term "absorb" also means that the drug composition may partially adsorb onto the pad. When the drug composition is absorbed into the pad, the active agent becomes entrapped within the pad and is released from the pad when the composition is transferred from the pad to a user's skin.

[24] As used herein, the term "acne" means a common inflammatory disease of the pilosebaceous glands characterized by comedones, papules, pustules, inflamed nodules, superficial pus-filled cysts, and (in extreme cases) canalizing and deep, inflamed, sometimes purulent sacs. Types of acne within the scope of the present subject matter include acne vulgaris or topical acne. "Acne" is caused by an interaction among hormones, keratin, sebum, and bacteria. One common bacterial causative agent is Propionibacterium acnes.

[25] As used herein, "affected area" refers to the area of skin afflicted with acne on a patient.

[26] As used herein, the terms "a combination amount sufficient," "an effective combination amount" "therapeutically effective combination amount" or "an effective amount of the combination of all refer to a combined amount of both the drug composition (the benzoyl peroxide pad) and the flowable composition that is effective to ameliorate symptoms associated with a skin disorder, for example, acne. As used herein, the term "combination" of a benzoyl peroxide pad with the flowable composition means the two elements can be delivered in combination therapy wherein the benzoyl peroxide pad is administered first, followed by the flowable composition, as well as wherein the flowable composition is delivered first, followed by a benzoyl peroxide pad. Likewise, the term "combination" further indicates that each of the benzoyl peroxide pad and the flowable composition can be delivered at the same time. The desired result can be either a subjective relief of a symptom(s) or an objectively identifiable improvement in the recipient of the dosage. Also contemplated are "combinations" of the benzoyl peroxide pad and the flowable composition with further compositions, as described herein.

[27] As used herein, "container" refers to any device configured sufficient to contain one or more elements of the kit according to the present subject matter without reacting with such elements. The container can refer to and/or comprise one or more of an outer container and an inner product container. For example, a product container can contain one of one or more benzoyl peroxide pads and a flowable composition. A product container can contain one or more benzoyl peroxide pads and a separate product container can contain the flowable composition. Each product container can contain a single dosage unit or multiple dosage units. Suitable containers can comprise one or more of a tub, a carton, a tin, a jar, a bottle, a packet, shrink-wrap, a tube, a blister package, an ampoule, and a pump. For example, a benzoyl peroxide pad can be contained in an inert packet and the flowable composition can be contained in a bottle, where the packet and the bottle are contained together in, for example, a shrink-wrapped carton, tin, or tub. [28] As used herein, "derivative" or "derivatives" refers to derivative(s) of the active compound(s) which possess the same pharmacological activity as the active compound(s) and which are neither biologically nor otherwise undesirable.

Derivatives of the active compounds include, without limitation, polymorphs, solvates, salts, N-oxides, hydrates, dehydrates, crystalline forms, anhydrous forms, amorphous forms, and mixtures thereof.

[29] As used herein, an "extended period of time" refers to the shelf life of the presently preferred compositions, including time spent on the shelf at a pharmacy as well as the entire time period after sale of the composition during which the composition remains effective for the indicated use.

[30] As used herein, "indicia" refers to any markings, texture, letters, numbers, pictures, and/or drawings, that conveys information to a user or patient. Indicia can comprise, for example, written instructions or a product label. pi] As used herein, "flowable composition" refers to any composition that comprises one or more agents suitable for the treatment of acne where the composition is flowable, that is, the composition has a viscosity that will permit displacement of the flowable material with or without the application of pressure. A flowable composition is manipulatable, is displaceable through a small to moderate sized orifice, and may be shaped or molded. Flowable compositions in this context include those having a consistency from that of an emulsion, suspension, or solution with a low viscosity or water-like consistency, to those of a high viscosity paste.

Suitable flowable compositions can comprise benzoyl peroxide wash compositions described herein.

[32] As used herein, "administered intermittently" refers to administration of the benzoyl peroxide pads and/or the flowable composition, alone or sequentially, at irregular time periods throughout a 24 hour period on an as needed basis.

[33] As used herein, a "patient" refers to an entity to whom the preferred drug compositions are being administered. Non-limiting examples of a patient in this regard include a mammal, an animal, and a human being. Preferably, the patient is a human being. The patient can be suffering from one or more skin disorders, particularly acne.

[34] As used herein, "pharmaceutically acceptable salts" or "salts" refers to salts of the active compound(s) which possess the same pharmacological activity as the active compound(s) and which are neither biologically nor otherwise undesirable. A salt can be formed with, for example, organic or inorganic acids. Non-limiting examples of suitable acids include acetic acid, acetylsalicylic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzoic acid, benzenesulfonic acid, bisulfic acid, boric acid, butyric acid, camphoric acid, camphorsulfonic acid, carbonic acid, citric acid, cyclopentanepropionic acid, digluconic acid, dodecylsulfic acid, ethanesulfonic acid, formic acid, fumaric acid, glyceric acid, glycerophosphoric acid, glycine, glucoheptanoic acid, gluconic acid, glutamic acid, glutaric acid, glycolic acid, hemisulfic acid, heptanoic acid, hexanoic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthylanesulfonic acid, naphthylic acid, nicotinic acid, nitrous acid, oxalic acid, pelargonic, phosphoric acid, propionic acid, saccharin, salicylic acid, sorbic acid, succinic acid, sulfuric acid, tartaric acid, thiocyanic acid, thioglycolic acid, thiosulfuric acid, tosylic acid, undecylenic acid, naturally and synthetically derived amino acids. [35] Non-limiting examples of base salts include ammonium salts; alkali metal salts, such as sodium and potassium salts; alkaline earth metal salts, such as calcium and magnesium salts; salts with organic bases, such as dicyclohexylamine salts; methyl-D-glucamine; and salts with amino acids, such as arginine, lysine, and so forth. Also, the basic nitrogen-containing groups can be quatemized with such agents as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dialkyl sulfates, such as dimethyl, diethyl, dibutyl, and diamyl sulfates; long chain halides, such as decyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides; asthma halides, such as benzyl and phenethyl bromides; and others. Water or oil-soluble or dispersible products are thereby obtained. Preferred salts include acetate, butyrate, hemisuccinate and phosphate. [36] As used herein, the term "sensitivity" refers to the degree of skin irritation or skin inflammation, as exemplified by parameters in suitable assays for measuring sensitivity, inflammation, irritation, and the like. One such assay is the Jordan-King assay.

[37] As used herein, "administered sequentially" refers to the administration of the benzoyl peroxide pad and the flowable composition, one after the other in any order, for example administration of the benzoyl peroxide pad followed by administration of the flowable composition, within a 24 hour period of time, preferably one shortly after the other.

[38] As used herein, "skin disorders" refers to disorders of the skin including, for example, acne, rosacea, psoriasis, folliculitis, perioral dermatitis, atopic dermatitis, impetigo, secondary skin infections, seborrhea, skin lesions, bacterial skin infections, and other inflammatory skin conditions.

[39] As used herein, "short-contact therapy" and "short-contact therapies" refer to the benzoyl peroxide pad composition and the flowable composition, or other compositions used herein, being formulated to be in contact with the skin for a limited amount of time. As short-contact therapies, it is preferable that the benzoyl peroxide pad composition and the flowable composition are removed from the affected area after a time of about 15 seconds to about 30 minutes. Preferably, the benzoyl peroxide pad composition and the flowable composition are removed after a time of about 30 seconds to about 120 seconds. More preferably, the benzoyl peroxide pad composition and the flowable composition are removed after a time of about 15 seconds to about 60 seconds. The benzoyl peroxide pad composition and the flowable composition may be in contact with the affected area for the same amount of time, or for different amounts of time. Optimally, the benzoyl peroxide pad composition and the flowable composition are removed using water. [40] The term "soap" refers to a substance used for washing and cleansing purposes, usually made by treating a fat with an alkali, such as sodium or potassium hydroxide, and consisting chiefly of the sodium or potassium salts of the acids contained in the fat.

[41] The term "synthetic surfactant" refers to a non-soap surfactant. Thus, a synthetic surfactant is not a soap product as defined above.

[42] As used herein, the terms "non-soap" and "soap-free" are used interchangeably and refer to a composition or compositions that do not contain soap. [43] As used herein, "storage stable" refers to the ability of the present compositions to have a long shelf life, including time spent on the shelf at a pharmacy as well as the entire time period after sale of the composition, during which time the composition maintains its effectiveness and pharmaceutically acceptable appearance. Accordingly, the present compositions are stable in that they exhibit a minimum amount of degradation during an extended period of storage. [44] As used herein, "suspension" refers to the relationship between the active agent and the liquid components of the benzoyl peroxide composition absorbed onto the pads herein. The active agent is preferably suspended within the drug composition, meaning that microscopic or nanoscopic particles of the active agent are dispersed within the liquid medium of the drug composition. The active particles are supported by the buoyancy of the liquid medium. The suspension of particles within the liquid medium enables the liquid medium to transport the particles into the pads, where the particles become entrained or entrapped within the voids of the pad. [45] The term "synergistic effective amount" refers to a combined amount of both the benzoyl peroxide pad and the flowable composition that is effective to cause a synergistic effect in the treatment of a skin disorder herein, such as acne. Synergy is a biological phenomenon in which the effectiveness of two components is more than additive, i.e., the effectiveness is greater than the equivalent concentration of either component alone. In certain aspects, the effectiveness of the combination therapy of the benzoyl peroxide pad and the flowable composition is synergistic. Thus, synergism is a result, or function, that is more than the sum of the results, or functions of individual elements.

[46] Other terms as used herein are meant to be defined by their well-known meanings in the art.

KU

[47] The present subject matter is directed to a kit comprising

[48] at least one pad containing a drug composition absorbed thereon, the drug composition comprising from about 2.5% to about 13% by weight benzoyl peroxide, from about 80% to about 90% by weight water, and from about 0.1 % to about 1.5% by weight of a surfactant system; and

[49] a container containing a flowable composition of one or more agents suitable for the treatment of acne. Benzoyl Peroxide Pad

[so] The preferred benzoyl peroxide pad compositions described herein are unique in that they exhibit remarkable stability. Since benzoyl peroxide is well- known for its oxidation properties, it is often difficult to formulate benzoyl peroxide containing compositions that exhibit long term stability. In this regard, the preferred compositions exhibit excellent stability for an extended period of time under normal storage conditions, particularly with respect to the active ingredient present in conjunction with the other components of the drug composition. The excellent storage stability of these preferred compositions solves long felt difficulties in formulating benzoyl peroxide compositions due to the extreme oxidative nature of benzoyl peroxide.

[51] Since the present benzoyl peroxide compositions have an increased stability and are absorbable on the present pads, they provide unexpected advantages over the prior art compositions. For example, the increased storage stability permits the presently preferred benzoyl peroxide compositions to be manufactured in greater quantities without fear that the compositions produced will be wasted. Further, the enhanced stability and absorbability on the pads provides the presently preferred benzoyl peroxide compositions with an enhanced effect in treating acne and other skin disorders treatable with benzoyl peroxide over the previously known compositions, which are not generally absorbable on pads.

[52] The enhanced stability of the preferred benzoyl peroxide pad compositions also provides greater control over degradates associated with benzoyl peroxide. As indicated above, benzoyl peroxide usually has very oxidative properties, often leading to the rapid degradation of compositions containing benzoyl peroxide and the formation of many degradates. The enhanced stability of the preferred benzoyl peroxide pad compositions herein provides greater control over degradate formation when compared with known benzoyl peroxide delivery systems. In this regard, the present benzoyl peroxide pad compositions are preferably able to maintain a purity of at least 90% and a concentration of degradation product(s) less than about 10% of the starting concentration of the benzoyl peroxide, as well as of the other essential ingredients in particularly preferred embodiments.

[53] As indicated above, the presently preferred benzoyl peroxide pad compositions are suspensions, with the active agent suspended in a liquid medium. The surfactant system helps to incorporate the active particles into the liquid medium. The use of a suspension for absorbing the benzoyl peroxide composition into and onto the pads provides a simpler composition over the benzoyl peroxide emulsions of the prior art. The preferred benzoyl peroxide compositions are simpler than the emulsions because, as non-emulsions, the preferred benzoyl peroxide compositions do not require two phases (a hydrophilic phase and a lipophilic phase) which are combined through the presence of an emulsifier. The preferred benzoyl peroxide compositions, on the other hand, use the surfactant system to aid in suspending the active particles in the liquid medium, and therefore do not require two different phases to be combined.

[54] The selection of certain components and amounts thereof in the presently preferred benzoyl peroxide pad compositions, as well as the preparation of compositions having a specific viscosity in the form of dispersions or suspensions, conveys these unique stability and absorbability characteristics to the presently preferred benzoyl peroxide pad compositions. In particular, the presence of a surfactant system, as well as a moisturizer, with the recited weight ratios of nonionic and anionic surfactants enhances the stability of the presently preferred benzoyl peroxide pad compositions, and aids in rendering these compositions well absorbable onto the pads for ease of administration to the patient. [55] The present benzoyl peroxide compositions are introduced to the pad as a suspension. The benzoyl peroxide present in the drug composition is pharmaceutical grade. The benzoyl peroxide component of the present benzoyl peroxide pad compositions is generally present at an amount of between about 2.5% to about 13% by weight of the total composition of benzoyl peroxide. In a preferred embodiment, the compositions contain from about 4% to about 8% by weight of the total composition of benzoyl peroxide. In a particularly preferred embodiment, the present compositions contain about 4% or about 8% by weight of benzoyl peroxide. The present compositions are unique in that they can be produced having a standard deviation of benzoyl peroxide present within + 0.07.

Surfactant System

[56] The present drug compositions can additionally preferably contain a surfactant system. Benzoyl peroxide is relatively insoluble in water. Accordingly, the surfactant system used herein is uniquely selected to provide the benzoyl peroxide with the ability to be incorporated into, for example, a water component of the present compositions to produce an overall benzoyl peroxide composition that is able to be absorbed onto a pad drug delivery system without the benzoyl peroxide and water forming an emulsion.

[57] In this regard, preferred surfactant systems herein may be present in the drug composition at an amount of about 0.1 % to about 1.5% by weight of the total composition. In a particularly preferred embodiment, the drug compositions may contain from about 0.4% to about 1 % by weight of the surfactant system. In a most preferred embodiment, the drug compositions may contain about 0.45% by weight of the surfactant system.

[58] The surfactant system preferably comprises a combination of a plurality of surfactants. In preferred embodiments in this regard, the surfactant system comprises at least one nonionic surfactant and at least one anionic surfactant. [59] In one embodiment in this regard, the surfactant system comprises at least one nonionic surfactant in an amount of from about 50% to about 95% by weight of the surfactant system and at least one anionic surfactant in an amount of from about 5% to about 50% by weight of the surfactant system. In a preferred embodiment, the surfactant system comprises at least one nonionic surfactant in an amount of from about 75% to about 85% by weight of the surfactant system and at least one anionic surfactant present in an amount of from about 15% to about 25% by weight of the surfactant system. In a particularly preferred embodiment, the surfactant system comprises at least one nonionic surfactant present in an amount of about 67% by weight of the surfactant system and at least one anionic surfactant present in an amount of about 33% by weight of the surfactant system.

[60] Accordingly, the surfactant system preferably comprises at least one nonionic surfactant. Non-limiting examples of nonionic surfactants useful in the present surfactant systems in this regard include alkanolamides, amine oxides, esterified carboxylic acids, ethoxylated alcohols, poloxamers, and mixtures thereof. In a preferred embodiment, the at least one nonionic surfactant of the surfactant system is a poloxamer.

[61] One of skill in the art will recognize that poloxamers useful herein include a nonionic polyoxyethylene-polyoxypropylene block co-polymer. Non-limiting examples of commercially available poloxamers usable in the present drug compositions are the Pluronic® line of products available from BASF Corporation. [62] The surfactant system of the present drug compositions may also preferably comprise at least one anionic surfactant. Non-limiting examples of anionic surfactants useful in this regard include carboxylates, amino acid derivatives, alkyl sulphates, alkyl ether sulfates, sulphonates, isethionates, taurates, sulfosuccinates, alkyl sulfoacetates, phosphates, alkyl phosphates, and mixtures thereof. In a preferred embodiment, the at least one anionic surfactant of the surfactant system is disodium lauryl sulfosuccinate.

[63] In a particularly preferred embodiment, the nonionic surfactant of the surfactant system is a poloxamer, while the anionic surfactant is disodium lauryl sulfosuccinate. In a further particularly preferred embodiment, the poloxamer is preferably present in the surfactant system in an amount of about 0.2% by weight of the drug composition, while disodium lauryl sulfosuccinate is present in an amount of about 0.1 % by weight of the drug composition.

[64] This combination of nonionic surfactant and anionic surfactant may act synergistically to allow optimal delivery of the benzoyl peroxide on the skin of the user. Moreover, by virtue of the specific formulations enumerated herein, the release and/or absorption of the active benzoyl peroxide from the preferred compositions may be attained slowly and gradually when the composition is topically applied to the skin, if desired, which can make it very pleasing for use by a patient.

Water

[65] The present benzoyl peroxide pad compositions may also contain water as an aqueous carrier. The water is present as a carrier for the benzoyl peroxide pad compositions, as well as a solvent for solubilizing and/or suspending the benzoyl peroxide in conjunction with the surfactant system. The water is preferably present in the benzoyl peroxide pad compositions in an amount of about 80% to about 90% by weight of the benzoyl peroxide pad composition. In a particularly preferred embodiment, the water is present in an amount of about 88% by weight of the benzoyl peroxide pad composition.

[66] The preferred compositions herein are preferably formed as a solution, or a dispersion in which the surfactant system aids in solubilization of the benzoyl peroxide. The optimization of the benzoyl peroxide pad composition viscosity is particularly important to the storage stability of the present compositions. Often, the viscosity of solutions will increase when the compositions are stored for long periods of time. The present benzoyl peroxide pad compositions, though, exhibit excellent stability with respect to the viscosity of the drug compositions, even after the compositions have been stored for a desired period of time.

Moisturizer

[67] In a preferred embodiment, the present benzoyl peroxide pad compositions may further comprise a moisturizer. In some cases, the benzoyl peroxide can dry out the region of the body to which the present compositions are applied. In these cases, it is helpful to include a moisturizer in the benzoyl peroxide pad compositions to help the body retain the moisture by combating the drying effect of the benzoyl peroxide.

[68] The moisturizer is preferably present in the present benzoyl peroxide pad compositions at a concentration of about 2% to about 6% by weight of the total composition. In a particularly preferred embodiment, the moisturizer is present at a concentration of about 4% by weight of the total composition. [69] Preferred, non-limiting examples of such moisturizers useful in the present benzoyl peroxide pad compositions include glycerin, pentylene glycol, butylene glycol, polyethylene glycol, sodium pyrrolidone carboxylate, alpha-hydroxy acids, beta-hydroxy acids, polyhydric alcohols, ethoxylated and propoxylated polyols, polyols, polysaccharides, panthenol, hexylene glycol, propylene glycol, octyldodecanol, dipropylene glycol, sorbitol, derivatives thereof, and mixtures thereof. In a preferred embodiment, the moisturizer included in the present benzoyl peroxide pad compositions comprises glycerin.

Gelling Agent

[70] The presently preferred benzoyl peroxide pad compositions may further comprise a gelling agent. This gelling agent can provide the present benzoyl peroxide pad compositions with a matrix for forming a low viscosity gel network. The gelling agent can form a three-dimensional network in the dispersant (the water and surfactant system in the present benzoyl peroxide pad compositions), allowing individual particles present in the gelling agent to be linked to one another more or less firmly via electro-static interaction.

[71] In a preferred embodiment, the gelling agent is present in the instant benzoyl peroxide pad compositions in an amount of about 0.2% to about 0.4% by weight. In a particularly preferred embodiment, the benzoyl peroxide pad compositions comprise from about 0.25% to about 0.35% by weight of the gelling agent. In a still further particularly preferred embodiment, the benzoyl peroxide pad compositions comprise about 0.3% by weight of the gelling agent.

[72] The gelling agent can be any substance that provides the necessary three- dimensional network within the dispersant. Preferred, non-limiting examples of gelling agents useful in this regard include various cellulose agents, such as hydroxyethylcellulose, cellulose gum, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum, gum arabic, gum tragacanth, locust bean gum, guar gum, other cellulosic polymers, derivatives thereof, and mixtures thereof.

[73] Other suitable gelling agents useful in the present benzoyl peroxide pad compositions can include sodium carbomer, carbomer, polyacrylic polymers, aqueous gelling agents, such as neutral, anionic, cationic polymers, carboxy vinyl polymers, such as carboxypolymethylene, derivatives thereof, and mixtures thereof. In a particularly preferred embodiment, the gelling agent is carbomer. [74] In this regard, a specific preferred gelling agent is a Carbopol® polymer (i.e. a polyacrylic polymer) such as is available from Noveon Inc., Cleveland, OH. Another particularly preferred gelling agent is a polyacrylic polymer, for example a copolymer of acrylic acid and a long chain alkyl methacrylate. This copolymer can be crosslinked with polyalkenyl ethers of polyalcohols, for example as with a Pemulen® polymer available from Noveon Inc., Cleveland, OH.

Pads

[75] The present benzoyl peroxide pads are used to deliver the benzoyl peroxide pad composition to a patient in need thereof. The pad allows for easy application of the drug compositions to the skin of a user. Accordingly, the pad is preferably made of a material in which the benzoyl peroxide composition is capable of being absorbed.

[76] In this regard, exemplary applicator pads useful in the present subject matter are made, by way of non-limiting example, from a plastic foam, a sponge, a woven or nonwoven natural or synthetic fiber or fabric, including gauze, felt, or cotton, or any other material capable of absorbing the present benzoyl peroxide pad compositions. In a preferred embodiment, the pad is made of synthetic or natural material and woven or non-woven material. In a particularly preferred embodiment, the pad is made of a non-woven synthetic material, for example without limitation, BBA Fiberweb®. The BBA Fiberweb® pad contains 75% rayon and 25% polypropylene. It is a thermal bonded fabric made by BBA Nonwoven Division, Bethune, S. C. The pad is preferably disposable.

[77] The pads useful herein can be composed of a single layer, or they can be formed of two or more layers. As will be apparent to a skilled artisan, for multiple layer pads, the various layers can be made of the same or different materials. The pads can also be of various forms or shapes, for example, with the substrate in a rectangular or washcloth-like shape, or alternatively, the substrate can be in the form of a glove, mitt or mitten. A wide variety of additional shapes are possible, such as oval, circular, etc. In a preferred embodiment, the pads are circular in shape.

Container

[78] The delivery systems of the present subject matter may also include a container. If present, the container holds the at least one pad and the benzoyl peroxide composition absorbed thereon.

[79] The container may contain one or more pads and is designed such that the benzoyl peroxide composition does not leak from the pads during storage. The container aids in preserving the pad(s) and benzoyl peroxide composition once it is sealed. In one embodiment of the present subject matter, the container may be any material that packages the pad with the benzoyl peroxide composition and does not degrade or leak the composition for a sufficient period of time, such as the shelf life of the product. In a preferred embodiment, the container comprises one or more sheets of plastic-lined foil material. The container is preferably fashioned from the sheets to hold one or more pads.

[80] In one embodiment, two sheets, which are larger than the pad or the dimensions of the pad when folded, are placed in the following layers: a bottom sheet, the pad, and the top sheet over the pad. The sides of the sheets meet because the pad is smaller than the sheets and is placed in the center of the sheets. At the sides of the sheets, heat and pressure is applied which causes the plastic lining of both sheets to melt and seal together, enclosing the pad. One of ordinary skill in the art will understand that time, heat, and pressure will vary according to the type of material and/or process used.

[81] If a plurality of pads is held within the container formed of a lined foil material, the container is preferably re-sealable in order to maintain the stability of the benzoyl peroxide compositions absorbed onto the pads.

[82] In an alternative embodiment, the container comprises a plastic or glass jar suitable for holding the pads and the benzoyl peroxide composition. The plastic or glass jar is made of a suitable plastic or glass material that does not react with the benzoyl peroxide composition, and may have an inner seal between the top of the jar and the lid of the jar. The inner seal helps maintain an inert atmosphere within the jar, thereby extending the shelf life of the benzoyl peroxide compositions absorbed onto the pads stored in the jar.

[83] When the container is a plastic jar, the plastic used to make the jar may comprise, without limitation, polyvinyl chloride, polyethylene, polypropylene, polyester, any other suitable plastic material, and mixtures thereof. Whether the jar is plastic or glass, it is preferred to tint the plastic or glass jar with a dye which may help to protect the benzoyl peroxide compositions from harmful ultraviolet rays. [84] A skilled artisan will recognize that any suitable container can be used to hold the at least one pad and benzoyl peroxide composition of the present subject matter. Preferably, the container is re-sealable and holds a plurality of pads.

Flowable Composition Benzoyl Peroxide Wash

[85] The present kits further include a flowable composition of one or more agents suitable for the treatment of acne. In a preferred embodiment in this regard, the flowable composition comprises, for example, a benzoyl peroxide wash intended for application to an affected area. The benzoyl peroxide wash can comprise or consist of benzoyl peroxide, a synthetic surfactant, and a moisturizer. The benzoyl peroxide wash preferably has a pH of 2 to 7.

[86] The benzoyl peroxide wash can comprise benzoyl peroxide. The amount of benzoyl peroxide present in the benzoyl peroxide wash is from about 1 % by weight to about 20% by weight of the benzoyl peroxide wash. Preferably, the benzoyl peroxide is present in the benzoyl peroxide wash at an amount of about 2.5% by weight to about 10% by weight of the benzoyl peroxide wash. [87] The benzoyl peroxide wash of the present subject matter can comprise water, an alpha hydroxy acid, a moisturizer, an isosorbide and a synthetic surfactant. The amount of water present in the benzoyl peroxide wash compositions of the present subject matter may be from about 30% by weight to about 70% by weight of the benzoyl peroxide wash. Preferably, the amount of water present is from about 35% by weight to about 55% by weight of the benzoyl peroxide wash, [ββ] Alpha hydroxy acids which are useful in the benzoyl peroxide wash of the present subject matter can comprise or consist of one or more pharmaceutically acceptable alpha hydroxy acids, such as, for example, glycolic acid, lactic acid, 2- hydroxydecanoic acid, 2-hydroxystearic acid, malic acid and mixtures thereof. Preferably, the alpha hydroxy acid is one that is commonly used in topical compositions for treating acne, such as glycolic acid or lactic acid. Most preferably, the alpha hydroxy acid is glycolic acid. The amount of alpha hydroxy acid present in the wash compositions of the present subject matter may be from about 0.1 % by weight to about 15% by weight, based upon the weight of the benzoyl peroxide wash. Preferably, the alpha hydroxy acid is present in an amount from about 1 % by weight to about 10% by weight of the benzoyl peroxide wash. [89] Moisturizers which may be included in the benzoyl peroxide wash of the present subject matter can comprise or consist of any pharmaceutically acceptable moisturizer, for example, one or more of sodium pyrollidone carboxylate, glycerin, glycolic acid, propylene glycol, sorbitol and mixtures thereof. Preferably, the moisturizer is sodium pyrollidone carboxylate. The amount of moisturizer present in the wash compositions of the present subject matter may be from about 0.5% by weight to about 20% by weight, based upon the weight of the benzoyl peroxide wash. Preferably, the moisturizer is present in an amount from about 1% by weight to about 15% by weight of the benzoyl peroxide wash.

[90] lsosorbides which are useful in the benzoyl peroxide wash of the present subject matter can comprise or consist of one or more pharmaceutically acceptable isosorbides. Such isosorbides include, for example, dimethyl isosorbide, diethyl isosorbide, ethylmethyl isosorbide and mixtures thereof. The isosorbide can be an alkyl ester of isosorbide, such as dimethyl isosorbide. The amount of isosorbide present in the compositions of the invention may be from about 0.05% by weight to about 20% by weight, based upon the weight of the benzoyl peroxide wash. Preferably, the isosorbide is present in an amount from about 0.05% by weight to about 10% by weight. pi] The benzoyl peroxide wash of the present subject matter can comprise a synthetic surfactant. Such synthetic surfactants can comprise, for example, sodium potassium lauryl sulfate, cocamidopropyl betaine, sodium cocoylisethionate, disodium cocoamphopropionate and mixtures thereof. Preferably, the synthetic surfactant is sodium potassium lauryl sulfate or cocamidopropyl betaine. The amount of synthetic surfactant present in these compositions may be from about 15% by weight to about 60% by weight, based upon the weight of the benzoyl peroxide wash. Preferably, the synthetic surfactant is present in an amount from about 25% by weight to about 40% by weight of the benzoyl peroxide wash. [92] In a particularly preferred embodiment of the present subject matter, the benzoyl peroxide wash comprises: a) water present in an amount from about 25% by weight to about 60% by weight of the composition; b) benzoyl peroxide present in an amount from about 1 % by weight to about 20% by weight of the composition; c) an alpha hydroxy acid selected from the group consisting of glycolic acid, lactic acid, 2- hydroxydecanoic acid, malic acid and mixtures thereof and present in an amount from about 0.1 % by weight to about 15% by weight of the composition; d) a moisturizer selected from the group consisting of sodium pyrollidone carboxylate, glycerin, propylene glycol, sorbitol and mixtures thereof and present in an amount from about 0.1 % by weight to about 15% by weight of the composition; e) an alkyl ester of isosorbide selected from the group consisting of dimethyl isosorbide, diethyl isosorbide, dipropyl isosorbide, ethylmethyl isosorbide and mixtures thereof and present in an amount from about 0.05% by weight to about 10% by weight of the composition; and f) a synthetic surfactant selected from the group consisting of cocamidopropyl betaine, sodium potassium lauryl sulfate, sodium cocoylisethionate, disodium cocoamphopropionate and mixtures thereof and present in an amount from about 15% by weight to about 60% by weight of the composition. [93] The preferred benzoyl peroxide wash described herein is unique in that it exhibits remarkable stability. As discussed herein, benzoyl peroxide is well-known for its oxidation properties. In this regard, the preferred benzoyl peroxide wash exhibits excellent stability for an extended period of time under normal storage conditions, particularly with respect to the active ingredient present in conjunction with the other components of the benzoyl peroxide wash. The excellent storage stability of the preferred benzoyl peroxide wash solves long felt difficulties in formulating benzoyl peroxide compositions due to the extreme oxidative nature of benzoyl peroxide. Since these benzoyl peroxide wash treatments have an increased stability, they provide unexpected advantages over the prior art compositions. For example, the increased storage stability permits the presently preferred benzoyl peroxide wash to be manufactured in greater quantities without fear that the wash produced will be wasted. Further, the enhanced stability provides the presently preferred benzoyl peroxide wash with an enhanced effect in treating acne and other skin disorders treatable with benzoyl peroxide over the previously known compositions.

Gelling Agent

[94] The presently preferred benzoyl peroxide wash may further comprise a gelling agent. This gelling agent provides the benzoyl peroxide wash with a matrix for forming a low viscosity gel network. The gelling agent forms a three-dimensional network in the dispersant, it being possible for individual particles present in the gelling agent to be linked to one another more or less firmly via electro-static interaction. In a preferred embodiment, the gelling agent is present in the instant compositions in an amount of about 0.2% to about 0.4% by weight. In a particularly preferred embodiment, the benzoyl peroxide wash compositions comprise about 0.25% to about 0.35% by weight of the gelling agent. In a still further particularly preferred embodiment, the benzoyl peroxide wash compositions comprise about 0.3% by weight of the gelling agent.

[95] The gelling agent can comprise or consist of any substance that provides the necessary three-dimensional network within the dispersant. Preferred, non-limiting examples of gelling agents useful in this regard include various cellulose agents, such as hydroxyethylcellulose, cellulose gum, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum, gum arabic, gum tragacanth, locust bean gum, guar gum, other cellulosic polymers, derivatives thereof, and mixtures thereof.

[96] Other suitable gelling agents useful in the present compositions can comprise sodium carbomer, carbomer, polyacrylic polymers, aqueous gelling agents, such as neutral, anionic, and cationic polymers, derivatives thereof, and mixtures thereof. [97] Exemplary polymers which may be useful in the preferred compositions can comprise carboxy vinyl polymers, such as carboxypolymethylene. In this regard, a preferred gelling agent is a Carbopol® polymer (i.e. a polyacrylic polymer) such as is available from Noveon Inc., Cleveland, OH. Another particularly preferred gelling agent is a polyacrylic polymer, for example a copolymer of acrylic acid and a long chain alkyl methacrylate. This copolymer can be crosslinked with polyalkenyl ethers of polyalcohols, for example as with a Pemulen® polymer available from Noveon Inc., Cleveland, OH.

Dermatoloaicallv Acceptable Excioients

[98] The benzoyl peroxide wash discussed herein can additionally comprise at least one dermatologically acceptable excipient commonly known to those of ordinary skill in the art as useful in topical compositions as described herein.

Formulations [99] The flowable composition, for example, the benzoyl peroxide wash, of the present subject matter can comprise any formulation suitable for topical application that flows. Flowable composition formulations can comprise one or more of a liquid, a suspension, an emulsion, a foam, a foamable liquid, a cream, a lotion, and a gel. The flowable composition can be packaged in any suitable container. Such suitable containers can comprise a bottle, a jar, an aerosol, a pressurized container, an airless pump, or an air pump, [loo] The flowable composition can comprise a pH of from about 2.0 to about 7.0.

Dermatoloqicallv Acceptable Excipients

[ioi] The preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions discussed herein can additionally comprise at least one dermatologically acceptable excipient commonly known to those of ordinary skill in the art as useful in topical compositions. Preferred, non-limiting examples of dermatologically acceptable excipients useful in these compositions are those selected from the group consisting of preservatives, colorants or pigments, anti-oxidants, radical scavengers, emulsifiers, humectants, pH modifiers, chelating agents, derivatives thereof, and mixtures thereof.

Preservatives

[102] The presently preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions may optionally further comprise at least one preservative. Preferred non-limiting examples of preservatives useful in this regard include propylene glycol, glycerol, butylene glycol, pentylene glycol, hexylene glycol, sorbitol, benzyl alcohol, ethanol, derivatives thereof, and mixtures thereof.

[103] The preservative is preferably present in the benzoyl peroxide pad composition in an amount of from about 0.1% to about 2.5% by weight of the overall weight of the benzoyl peroxide pad composition.

Anti-oxidants

[104] The presently preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions may optionally further comprise at least one anti-oxidant. Preferred non-limiting examples of antioxidants useful in this regard include ascorbic acid, ascorbyl esters of fatty acids, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate, tocopherol, tocopherol sorbate, tocopherol acetate, butylated hydroxy benzoic acid, thioglycolates, persulfate salts, θ-hydroxy^.δ.Z.δ-tetramethylchroman^-carboxylic acid, lipoic acid, gallic acid, propyl gallate, uric acid, sorbic acid, lipoic acid, amines, N.N-diethylhydroxylamine, N-acetyl-L-cysteine, amino-guanidine, sulfhydryl compounds, glutathione, dihydroxy fumaric acid, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, 1 -methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin, rosemary extracts, derivatives thereof, and mixtures thereof.

Humectants

[105] The presently preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions may optionally further contain a humectant. Preferred, non-limiting examples of humectants useful in this regard include sorbitol, sorbitol syrup, E965 maltitol, maltitol, maltitol syrup, E1200 polydextrose, E1518 glyceryl triacetate, triacetin, glyceryl triacetate, 1 ,2,3- propanetriyl triacetate, 1 ,2,3-propanetriol triacetate, triacetylglycerol, E1520 propylene glycol, 1 ,2-propanediol, 1 ,2-dihydroxypropane, methylethylene glycol, propane-1 ,2-diol, E420 sorbitol, propylene glycol, polyethylene glycol (PEG) esters, PEG-20 stearate, PEG-40 stearate, PEG-150 stearate, PEG-150 distearate, PEG- 100 stearate, laureth-12, ceteareth-20, laureth-23, glycereth-7, glycereth-12, glycereth-26, PEG-4, PEG-6, PEG-8, PEG-12, PEG-32, PEG-75, PEG-150, derivatives thereof, and mixtures thereof. pH Modifiers

[106] The presently preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions may optionally further contain a pH modifier. Preferred non-limiting examples of pH modifiers useful in this regard include inorganic hydroxides, inorganic oxides, inorganic salts of weak acids, inorganic acids, organic acids, derivatives thereof, and mixtures thereof. [107] Preferred, non-limiting examples of inorganic hydroxides useful in this regard include ammonium hydroxide, alkali metal hydroxide, alkaline earth metal hydroxides, derivatives thereof, and mixtures thereof.

[108] Preferred non-limiting examples of inorganic hydroxides useful herein include ammonium hydroxide, monovalent alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, divalent alkali earth metal hydroxides such as calcium hydroxide and magnesium hydroxide, derivatives thereof, and mixtures thereof. [109] Preferred, non-limiting examples of inorganic oxides useful herein include magnesium oxide, calcium oxide, derivatives thereof, and mixtures thereof, [no] Preferred, non-limiting examples of inorganic salts of weak acids useful herein include ammonium phosphate (dibasic), alkali metal salts of weak acids such as sodium acetate, sodium borate, sodium metaborate, sodium carbonate, sodium bicarbonate, sodium phosphate (tribasic), sodium phosphate (dibasic), potassium carbonate, potassium bicarbonate, potassium citrate, potassium acetate, potassium phosphate (dibasic), potassium phosphate (tribasic), alkaline earth metal salts of weak acids such as magnesium phosphate and calcium phosphate, derivatives thereof, and mixtures thereof.

[mi Preferred, non-limiting examples of inorganic acids useful herein include hydrochloric acid, hydrofluoric acid, hydrobromic acid, nitric acid, nitrous acid, hydrocyanic acid, perchloric acid, chlorous acid, sulfurous acid, hypochlorous acid, phosphoric acid, acetic acid, sulfuric acid, derivatives thereof, and mixtures thereof.

[112] Preferred, non-limiting examples of organic acids useful herein include lactic acid, citric acid, glutamic acid, methanoic acid, ethanoic acid, phenol, monochloroethanoic acid, dichloroethanoic acid, trichloroethanoic acid, butanoic acid, salicylic acid, glycolic acid, and mixtures thereof.

[113] Further, mixtures of any of the above-mentioned pH modifiers are also contemplated as within the scope of the present compositions.

Chelating Agents

[114] The presently preferred benzoyl peroxide pad compositions and/or flowable compositions including benzoyl peroxide wash compositions may optionally further comprise a chelating agent. Preferred non-limiting chelating agents useful in this regard can comprise citric acid, isopropyl (mono) citrate, stearyl citrate, lecithin citrate, gluconic acid, tartaric acid, oxalic acid, phosphoric acid, sodium tetrapyrophosphate, potassium monophosphate, sodium hexametaphosphate, calcium hexametaphosphate, sorbitol, glycine (aminoacetic acid), methyl glucamine, triethanolamine (trolamine), EDTA, DEG (dihydroxyethylglycine), DPTA (diethylene triamine pentaacetic acid), NTA (Nitrilotriacetic Acid), HEDTA (N-(hydroxyethyl)- ethylenetriaminetriacetic acid), aminocarboxylates, dimercaperol (BAL), larixinic acid (Maltol), unidentate ligands (fluoride and cyanide ions), diphenylthiocarbazone, 0- phenanthroline, barium diphenylamine sulfonate, sodium glucoheptonate, 8- hydroxyquinoline, olefin complexes (such as dicyclopentadienyl iron), porphyrins, phosponates, pharmaceutically acceptable salts thereof, derivatives thereof, and mixtures thereof.

[us] In addition to those enumerated above, any other surfactant, moisturizer, gelling agent, preservative, colorant or pigment, antioxidant, radical scavenger, emulsifier, humectant, pH modifier, chelating agent, or other dermatologically acceptable excipient commonly known to those of ordinary skill in the art as useful in topical compositions is contemplated as useful in the compositions described herein. Further, any non-toxic, inert, and effective topical carrier may be used to formulate the compositions described herein.

[116] Well-known carriers used to formulate other topical therapeutic compositions for administration to humans will be useful in these compositions. Examples of such components that are well known to those of skill in the art are described in The Merck Index. Thirteenth Edition, Budavari et al., Eds., Merck & Co., Inc., Rahway, NJ. (2001 ); the CTFA (Cosmetic, Toiletry, and Fragrance Association) International Cosmetic Ingredient Dictionary and Handbook. Tenth Edition (2004); and the "Inactive Ingredient Guide", U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Office of Management, http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm, the contents of which are hereby incorporated by reference in their entirety. Examples of such useful pharmaceutically acceptable excipients, carriers and diluents include distilled water, physiological saline, Ringer's solution, dextrose solution, Hank's solution, and DMSO, which are among those preferred for use herein.

[117] These additional other inactive components, as well as effective formulations and administration procedures, are well known in the art and are described in standard textbooks, such as Goodman and Gillman's: The Pharmacological Bases of Therapeutics. 8th Ed., Gilman et al. Eds. Pergamon Press (1990) and Remington's Pharmaceutical Sciences, 17th Ed., Mack Publishing Co., Easton, Pa. (1990), both of which are incorporated by reference herein in their entirety.

Methods of Treatment

[118] Another embodiment of the present subject matter pertains to a method for treating acne comprising administering to a patient in need thereof a combination of products comprising a first product comprising at least one pad containing a benzoyl peroxide composition absorbed thereon, said benzoyl peroxide composition comprising from about 2.5% to about 13% by weight benzoyl peroxide, from about 80% to about 90% by weight water, and from about 0.1 % to about 1.5% by weight of a surfactant system; and a second product comprising a container containing a flowable composition of one or more agents suitable for the treatment of acne.

[119] In an embodiment of the present subject matter, the benzoyl peroxide composition and the flowable composition synergistically treat acne. Accordingly, the benzoyl peroxide composition and the flowable composition can be administered in a synergistically effective amount.

[120] An embodiment of the present subject matter pertains to a method for treating acne comprising administering to a patient in need thereof a combination of products where one of the first product and the second product is administered in the morning and the other is administered at night.

[121] Another embodiment of the present subject matter pertains to a method for treating acne comprising administering to a patient in need thereof a combination of products where the first product and the second product are administered sequentially.

[122] A further embodiment of the present subject matter pertains to a method for treating acne comprising administering to a patient in need thereof a combination of products where the first product and the second product are administered intermittently.

[123] The present subject matter also contemplates the treatment of other skin disorders by applying the present benzoyl peroxide pad compositions and flowable compositions to the skin of a patient. Exemplary specific skin disorders, other than acne, treatable by the present compositions include but are not limited to impetigo, rosacea, atopic dermatitis, secondary skin infections, seborrhea, skin lesions, and bacterial skin infections. In a preferred embodiment, the skin disorder or condition improves following treatment with the present benzoyl peroxide pad compositions and flowable compositions.

[124] In an embodiment of the present method, the flowable composition, for example, a benzoyl peroxide wash, can be topically administered to an affected area before the benzoyl peroxide pad is administered thereto. When the flowable composition, for example, a benzoyl peroxide wash, is administered before the benzoyl peroxide pad, the benzoyl peroxide wash removes reactive materials from the surface of the skin. The reactive materials include without limitation dead skin cells, dirt, excess sebum and microbes. If not removed by the benzoyl peroxide wash, the reactive materials removed by the benzoyl peroxide wash may be oxidized by the benzoyl peroxide pad, thus contributing to the irritation associated with the benzoyl peroxide pad composition. By removing the reactive materials prior to administering the benzoyl peroxide pad composition, the reactive materials are no longer present to be oxidized by the benzoyl peroxide. [125] In another embodiment of the present methods, the flowable composition, for example, a benzoyl peroxide wash, can be topically administered to an affected area after the benzoyl peroxide pad is administered thereto.

[126] In a further embodiment of the present inventive subject matter, the flowable composition, for example, a benzoyl peroxide wash, can be topically applied to an affected area at the same time as the benzoyl peroxide pad. By administering the benzoyl peroxide wash at the same time as the benzoyl peroxide pad, the irritating and oxidizing qualities of the benzoyl peroxide are diluted, resulting in reduced irritation of the affected area. Besides diluting the benzoyl peroxide, the benzoyl peroxide wash may also remove reactive materials from the surface of the skin prior to the oxidation of the skin by the benzoyl peroxide.

[127] As discussed herein, acne is a condition of the human skin characterized by an excess flow of sebum, or skin oil, from the sebaceous glands located in the pilosebaceous apparatus. The usual manifestations of acne are papules, pustules, or cysts, often contaminated with bacteria which cause secondary infections. Acne is particularly characterized by the presence of comedones, inflammatory papules, pustules, cysts, or lesions. The effect of acne ranges from slight skin irritation and pitting to disfiguring scars.

[128] Benzoyl peroxide is a strong oxidizing agent that has been shown to be effective in the treatment of acne. In particular, benzoyl peroxide is effective at reducing the number of comedones, inflammatory papules, pustules, cysts and lesions. Benzoyl peroxide is also effective at reducing the microbial count associated with the secondary infection often formed in an acne-affected area of skin. However, the efficacy of benzoyl peroxide can be reduced by the presence of other reactive materials on the affected area of skin. [129] The methods of the present subject matter result in the reduction of irritation associated with benzoyl peroxide. The reduction of irritation may be measured by the absence of skin redness normally associated with the topical application of benzoyl peroxide. The reduction of irritation may also be manifested by a lack of dryness of the affected area, as well as a lack of pain that accompanies oxidation of materials on the skin by the benzoyl peroxide. In a particularly preferred embodiment, the irritation associated with the benzoyl peroxide pad composition is completely reduced, meaning that no irritation occurs following administration of the benzoyl peroxide pad composition to the affected area.

[130] The methods of the present subject matter are also directed to enhancing the efficacy of a benzoyl peroxide pad composition in treating acne. The efficacy of the benzoyl peroxide treatment is enhanced by topically administering a flowable composition, for example, a benzoyl peroxide wash, to the affected area of skin. [131] The present method enhances the efficacy of the benzoyl peroxide pad composition, resulting in a reduction of the number of comedones, inflammatory papules, pustules, cysts and lesions. By including the step of topically administering a flowable composition to the affected area, the number of comedones, inflammatory papules, pustules, cysts and lesions is reduced by about 20% to about 80%. Preferably, the number of comedones, inflammatory papules, pustules, cysts and lesions is reduced by about 40% to about 60%. More preferably, the number of comedones, inflammatory papules, pustules, cysts and lesions is reduced by about 50%. The reduction in the number of comedones, inflammatory papules, pustules, cysts and lesions is observed when compared to the application of the benzoyl peroxide pad compositions without the concomitant administration of the flowable composition. [132] The enhancement of treatment with the benzoyl peroxide pad composition also results in a reduction of the irritation caused by the benzoyl peroxide pad composition. By reducing the irritation, the affected area of skin of the user will not exhibit as much redness as a user that uses the benzoyl peroxide pad composition without the topical administration of a flowable composition. Optimally, the method of the present subject matter will result in the elimination of the irritation resulting from treatment with the benzoyl peroxide pad composition. The enhancement of the efficacy of the benzoyl peroxide pad composition preferably results in from about 30% to about 70% reduction in the redness of the affected area. More preferably, the enhancement of the efficacy of the benzoyl peroxide pad composition results in from about 40% to about 60% reduction in the redness of the affected area. Most preferably, the enhancement of the efficacy of the benzoyl peroxide pad composition results in about 50% reduction of the redness of the affected area. The determination of the reduction in redness of the affected area is observed when compared to the application of the benzoyl peroxide pad composition without the concomitant administration of the flowable composition.

[133] The enhancement of the efficacy of the benzoyl peroxide pad composition also results in a faster return of the affected area to normal skin conditions, i.e., skin that is no longer affected by acne. Related to this result of the enhancement of the efficacy of the benzoyl peroxide pad composition is that the appearance of the skin improves at a greater rate than observed without the concomitant administration of the flowable composition. Acne manifests itself in the affected area by the appearance of redness, comedones, inflammatory papules, pustules, cysts and lesions. Likewise, the strong oxidization properties of the benzoyl peroxide act on the skin to produce irritation in the form of redness, dryness and slight pain. The step of topically administering a flowable composition helps the skin to recover from the effects of acne, as well as the effects the benzoyl peroxide, at a quicker rate than if the flowable composition was not applied to the affected area. [134] Preferably, the enhancement of the efficacy of the benzoyl peroxide pad composition results in a return of the affected area to its normal state and improvement in the appearance of the affected area within a time that is about one- half of the time required without the topical administration of the flowable composition. More preferably, the time is about one-third of the time required without the topical administration of the flowable composition. Most preferably, the time is about one-quarter of the time required without the topical administration of the flowable composition.

Combination Therapy

[135] In another preferred embodiment, the present kit comprising a first product comprising at least one benzoyl peroxide pad containing a benzoyl peroxide composition absorbed thereon and the present second product comprising a container containing a flowable composition of one or more agents suitable for the treatment of acne may be used in combination with an additional pharmaceutical or cosmetic dosage form to enhance their effectiveness in treating dermatological disorders described herein. In this regard, the present compositions may be administered as part of a regimen additionally including any other cosmetic, pharmaceutical and/or pharmaceutical dosage form known in the art as effective for the treatment of acne generally, or one of these disorders specifically. [136] Such additional dosage forms can comprise one or more of a soap-free cleanser and a barrier repair composition that repairs skin damage, as well as an additional cleanser. Soap-Free Cleanser

[137] The soap-free cleanser can comprise or consist of water, at least one emollient, a surfactant and at least one preservative.

[138] The soap-free cleanser of the present subject matter contains water. The amount of water present in the soap-free cleanser preferably is from about 85% by weight to about 95% by weight of the soap-free cleanser. More preferably, the amount of water present in the soap-free cleanser is from about 88% by weight to about 92% by weight of the soap-free cleanser. Most preferably, the amount of water present in the soap-free cleanser is from about 90% by weight to about 92% by weight of the soap-free cleanser.

[139] The soap-free cleanser of the present subject matter also preferably comprises at least one emollient. Preferably, the soap-free cleanser comprises a mixture of two or more emollients. Emollients are components which soften or soothe the skin. Thus, the emollients present in the soap-free cleanser aid in reducing the irritation associated with the benzoyl peroxide treatment, as well as enhancing the efficacy of the benzoyl peroxide treatment.

[140] Emollients useful in the soap-free cleansers of the present subject matter include, without limitation, vegetable oils, coconut oil, palm glycerides, olea europaea, extracts thereof, derivatives thereof, and mixtures thereof. Other non- limiting examples of specific emollients useful in the present soap-free cleansers include glycerin, pentylene glycol, butylene glycol, polyethylene glycol, sodium pyrrolidone carboxylate, α-hydroxy acids, β-hydroxy acids, polyhydric alcohols, including stearyl alcohol, ethoxylated and propoxylated polyols, polyols, polysaccharides, panthenol, hexylene glycol, propylene glycol, dipropylene glycol, sorbitol and mixtures thereof. In a preferred embodiment, the at least one emollient is a mixture of propylene glycol and stearyl alcohol.

[141] The amount of the at least one emollient present in the soap-free cleanser is typically from about 2.5% weight to about 10% by weight of the soap-free cleanser. Preferably, the at least one emollient or combination of emollients is present at an amount of from about 5% by weight to about 10% by weight of the soap-free cleanser. More preferably, the emollients are present in an amount of about 7.5% by weight of the soap-free cleanser.

[142] The soap-free cleanser of the present subject matter may also further comprise a surfactant. The surfactant aids in the removal of oils and other organic materials from the affected area when the soap-free cleanser is administered thereto.

[143] Surfactants useful in the soap-free cleanser of the present subject matter can comprise or consist of one or more of a betaine, an amine oxide, an amphoteric surfactant, a sulfate, an isothionate, a sulfoacetate, a sarcosunate, a phosphate, and a mixture of any two or more thereof. Suitable surfactants can comprise or consist of, without limitation, one or more of sodium lauryl sulfate, sodium laureth sulfate, ammonium lauryl sulfate, ammonium laureth sulfate, disodium laureth sulfosuccinate, disodium ricinoleamido monoethanolamide sulfosuccinate, sodium cocoyl isethionate, sodium methyl oleoyl taurate, sodium methyl cocoyl taurate, sodium laureth-13 carboxylate, sodium Cu-1₆ olefin sulfonate, sodium laureth-4 phosphate, laureth-3 phosphate, triethylanolamine lauryl sulfate, magnesium lauryl sulfate, sodium tridecyl sulfate, and alpha-olefin sulfate and mixtures thereof. In a preferred embodiment, the surfactant is sodium cocoyl isethionate. [144] The surfactant is preferably present in the soap-free cleanser in an amount of about 0.25% by weight to about 2% by weight of the soap-free cleanser. More preferably, the amount of surfactant is from about 0.45% by weight to about 1.5% by weight of the soap-free cleanser. Most preferably, the amount of surfactant is about 0.7% by weight of the soap-free cleanser.

[145] The soap-free cleanser may also include at least one preservative. The presence of at least one preservative provides sufficient preservative activity adequate to minimize and manage the risk of microbial contamination during storage or use of the soap-free cleanser. In other words, the at least one preservative present in the soap-free cleanser provides the soap-free cleanser with a long shelf- life. Preferably, more than one preservative is present in the soap-free cleanser. [146] Preservatives useful in the soap-free cleanser include, without limitation, propylene glycol, glycerol, butylene glycol, pentylene glycol, hexylene glycol, sorbitol, benzyl alcohol, ethanol, methylparaben, propylparaben, butylparaben, derivatives thereof, and mixtures thereof. In a preferred embodiment, the soap-free cleanser contains a combination of methylparaben, propylparaben, and butylparaben. [147] The preservatives are preferably present in the soap-free cleanser in a total amount of about 0.1 % by weight to about 0.5% by weight of the soap-free cleanser. More preferably, the preservatives are present in a total amount of about 0.3% by weight of the soap-free cleanser.

Additional Cleanser

[148] The present methods may further include the step of topically administering an addtional cleanser to the affected area. The additional cleanser may be a solid, such as a bar, a cream, a liquid or a powder. Preferably the cleanser is a bar and comprises, without limitation, one or more of cleansing agents, surfactants, emollients, keratolyses, alkalis, antimicrobial agents, colorants, fragrances, opacifiers, preservatives, processing aids, and the like. The additional cleanser may further optionally contain an active ingredient or ingredients, such as benzoyl peroxide.

[149] Suitable surfactants useful in the additional cleanser may include, without limitation, cocamidopropyl betaine, sodium or potassium lauryl sulfate, sodium cocoylisethionate, disodium cocoamphopropionate and mixtures thereof.

[150] Emollients useful in the additional cleansers of the present subject matter include, without limitation, vegetable oils (for example, castor oil), coconut oil, mineral oil, palm glycerides, olea europaea, extracts thereof, derivatives thereof, and mixtures thereof. Other non-limiting examples of specific emollients useful in the present additional cleansers include glycerin, cetearyl alcohol, pentylene glycol, butylene glycol, polyethylene glycol, sodium pyrrolidone carboxylate, α-hydroxy acids, β-hydroxy acids, polyhydric alcohols, including stearyl alcohol, ethoxylated and propoxylated polyols, polyols, polysaccharides, panthenol, hexylene glycol, propylene glycol, dipropylene glycol, sorbitol and mixtures thereof.

[151] Keratolytic agents useful in the additional cleansers of the present subject matter include, without limitation, alpha-hydroxy acids, such as lactic acid, salicylic acid, ascorbic acid, calcium pantothenate, acetic acid, podophyllum resin, zinc chloride, and mono-, di-, or trichloroacetic acid.

[152] The additional cleanser may optionally contain benzoyl peroxide. The amount of benzoyl peroxide present in the additional cleanser, if present, is from about 1% by weight to about 20% by weight of the additional cleanser. Preferably, the benzoyl peroxide is present in the additional cleanser at an amount of about 2.5% by weight to about 10% by weight of the additional cleanser.

[153] In a preferred embodiment, the additional cleanser is a bar and comprises one or more of benzoyl peroxide, cetearyl alcohol, cocamidopropyl betaine, corn starch, glycerin, hydrogenated castor oil, lactic acid, mineral oil, optical brighteners, PEG-14M, potassium lauryl sulfate, potassium phosphate, silica, sodium lauryl sulfate, sodium sulfate, titanium dioxide and water.

Barrier Repair Composition

[154] Suitable barrier repair compositions can comprise those taught in US Patent No. 7,001 ,604 hereby incorporated herein by reference in its entirety. Such barrier repair compositions can comprise at least one lamellar substance which forms lamellar structures with water, the lamellar substance being selected from the group consisting of monoglycerides, diglycerides, distilled medium-chain monoglycerides, sphingolipids, phospholipids, fatty alcohols, fatty acids, soaps, mono-esters of fatty acids, di-esters of fatty acids, sucrose, glucose, glucosidic condensation products of fatty alcohols with glucose and/or sucrose, furanosidic condensation products of fatty alcohols with glucose and/or sucrose, pyranosidic condensation products of fatty alcohols with glucose and/or sucrose, mono-esters of glucosides with fatty acids dehvates, diesters of glucosides with fatty acids derivates, sterols, mono-esters of fatty acids and sterols, diesters of fatty acids and sterols, glycol derivates of sterols, and mixtures thereof; an additive selected from the group consisting of methyl glycine, dimethylglycine, methyl methionine and mixtures thereof; S- adenosylmethionine and/or at least one compound having at least one functional group of formula I:

-CH₂-N⁺-(CH₃)₃ (formula I) the at least one compound excluding quaternary ammonium sufactants, and being selected from the group consisting of betaine, acetyl-choline, choline, glycerophosphocholine, phosphatidylcholine, lysophosphatidyicholine, carnitine, acylcamitine, sphingomyeline, and mixtures, derivates and metabolites thereof; and optionally, water.

[155] In addition to the benzoyl peroxide, the present additional compositions may further contain other active ingredients readily known to those of skill in the art as useful in the topical treatment of acne. Exemplary additional active ingredients include, but are not limited to, macrolide antibiotics, bactericidal drugs, bacteriostatic drugs, cleansing agents, absorbents, anti-infective agents, anti-inflammatory agents, astringents (drying agents that precipitate protein and shrink and contract the skin), emollients (skin softeners), keratolyses (agents that soften, loosen, and facilitate exfoliation of the squamous cells of the epidermis), and mixtures thereof. [156] Exemplary macrolide antibiotics contemplated as optionally within the scope of the present subject matter include, but are not limited to, Azithromycin, Clarithromycin, Erythromycin, Lincomycin, and mixtures thereof. The macrolides are similar in structure and activity. All the macrolides are easily absorbed and all are primarily bacteriostatic and bind to the 5OS subunit of the ribosome, thus inhibiting bacterial protein synthesis. These drugs are active against aerobic and anaerobic gram-positive cocci, with the exception of enterococci, and against gram-negative anaerobes and useful in combination with the present compositions. [157] Exemplary bactericidal drugs (i.e., they kill bacteria) contemplated as optionally within the scope of the present subject matter include, but are not limited to, penicillins, cephalosporins, vancomycin, aminoglycosides, quinolones, and polymyxins.

[158] Exemplary bacteriostatic drugs (i.e., they slow bacterial growth) contemplated as optionally within the scope of the present subject matter include, but are not limited to, erythromycin, tetracyclines, chloramphenicol, clindamycin, lincomycin, clarithromycin, azithromycin, and sulfonamides. However, it is well know that some bactericidal drugs may be bacteriostatic against certain microorganisms and vice versa. These drugs are well known in the art and may be found, for example, in The Merck Manual of Diagnosis and Therapy. 13th edition, Section 13, Chapter 153 Antibacterial Drugs, 2001 , incorporated herein by reference in its entirety. [159] Furthermore, the preferred formulations herein may be used with adjunct therapies and treatments, such as pre-washing with common soaps, and mild detergents. However, careful selection of such adjunct therapies is important when treating skin disorders such as acne since antibacterial soaps and abrasive soaps may increase irritation and make it difficult to use follicular drugs. Such follicular drugs may include topical antibiotics and antiseptics, as well as intralesional corticosteroids.

[160] In superficial pustular acne, the topical drug compositions may be used in combination with one of the follicular drugs.

[161] Sunlight therapy can be useful in combination with the present subject matter. Sunlight is known to cause mild dryness and slight scaling and is usually helpful. Since sunlight is not always available, some benefit may be obtained with a sunlamp.

[162] Another combination therapy involves azelaic acid cream 20%, which has antiproliferative and antibacterial effects, and is known to be effective in comedonal or inflammatory acne.

[163] An additional combination therapy contemplated herein is topical tretinoin (retinoic acid) in 0.025%, 0.05%, or 0.1 % cream, 0.05% liquid, or 0.01% or 0.025% gel. Also, a new topical retinoid, Differin® brand adapalene 0.1 % gel, Galderma Laboratories, San Antonio, TX, was recently approved in the USA and may be useful since it may be slightly less irritating than topical tretinoin. Other retinoids which may be useful in combination therapy include Panretin®, containing alitretinoin, and Targretin®, containing bexarotene. Since retinoids must be applied carefully and at night to avoid excessive irritation, a regimen in combination with these drugs may be used over time to achieve results. For example, retinoid therapy may be initiated and then followed on with once a day treatment in accordance with the present subject matter. Exposure to sunlight when using retinoids and concurrent use of other drugs are restricted to prevent severe irritation. However, a back-to-back alternating regimen over a period of weeks or months time may be useful. With tretinoin or adapalene, acne may worsen at first; improvement usually requires ≥ 3 to 4 weeks.

[164] Other topical drugs include OTC drugs, various sulfur-resorcinol combinations, and oral antibiotics may also be helpful in combination with the present subject matter when treating acne.

[165] Similarly, an anti-acne agent other than those specified herein, or an additional topical pharmaceutically active agent, can be added to the present preferred compositions to enhance their effectiveness. Accordingly, this additional agent or additional pharmaceutical dosage form can be applied to a patient either directly or indirectly, and concomitantly or sequentially, with the preferred compositions described herein.

[166] Further, in this embodiment, simultaneous application of the preferred compositions with administration of an oral antibiotic may provide synergistic beneficial effects in the treatment of acne. Such synergistic effects may be enhanced by the simultaneous topical application of the preferred compositions herein with oral administration of the antibiotics.

Methods of Production Benzoyl Peroxide Pad

[167] The present subject matter is also directed to a method for making the preferred benzoyl peroxide pad compositions and delivery systems. A preferred method for making the benzoyl peroxide pad compositions and delivery systems comprises:

1 ) Adding water to a suitable vessel and heating the water to about 60-80⁰C;

2) Adding a non-ionic surfactant and an anionic surfactant to the water vessel;

3) Cooling the above mixture to a temperature of about 20-25⁰C while maintaining mixing of the mixture;

4) In a separate vessel, adding this mixture with water and benzoyl peroxide and milling the resultant mixture to reduce particle size to no greater than 60 microns;

5) Adding water to the mixture from step 4) and mixing for at least 30 minutes; and

6) Absorbing the mixture from step 5) onto and into suitable pads. [168] In a preferred embodiment, a moisturizer and a preservative are added to the water vessel in step 2) along with the non-ionic surfactant and the anionic surfactant. In a further preferred embodiment, the non-ionic surfactant, moisturizer, preservative, and anionic surfactant are successively added to the water vessel

[169] In another preferred embodiment, a gelling agent is added to the water vessel prior to the step 2) above. According to this further step, the gelling agent/water mixture is mixed until the gelling agent is suitably hydrated. In a particularly preferred embodiment, the gelling agent/water mixture will be mixed for at least about 15 minutes.

[170] In still another preferred embodiment, a 1-5% sodium hydroxide solution containing purified water and sodium hydroxide is prepared in a separate container by mixing the solution with a spatula until the sodium hydroxide is dissolved. This solution can then be added to the mixture of step 4) above and mixed for at least 10 minutes.

[171] In another alternative preferred embodiment, the pH of the mixture from step

5) above can be adjusted to at least a pH of at least 5, by adding a sodium hydroxide solution to the mixture from step 5) above.

Flowable Composition

[172] The present subject matter is also directed to a method for making the flowable compositions. Benzoyl Peroxide Wash

[173] The benzoyl peroxide wash of the present subject matter is preferably prepared by the following method:

1 ) Water is added to a suitable vessel;

2) The water is heated to a temperature between 6O⁰C and 7O⁰C;

3) The synthetic surfactant is added to the water under stirring;

4) The resultant mixture is allowed to cool;

5) While cooling, the alpha hydroxy acid, moisturizers and isosorbides are added to the solution while continually stirring;

6) When the temperature of the solution fell to between 25⁰C and 35°, the benzoyl peroxide and preservatives are added to the solution under continuous stirring;

7) The resultant suspension is then passed through a homogenizer until a smooth product is obtained;

8) The pH of the product is then adjusted to a pH of 2 to 7.

Dosage

[174] To be effective, the route of administration for the compositions used in the present methods and pharmaceutical compositions must readily affect the target areas. In particular, acne is known to affect the face, neck, back, ears, and scalp. Moreover, it will be understood that a useful dosage of benzoyl peroxide pad can be administered in a single or multiple dosage units to provide the desired therapeutic effect. Likewise, a useful dosage of the flowable composition can be administered in a single or multiple dosage units to provide the desired therapeutic effect. [175] The preferred benzoyl peroxide compositions and/or flowable compositions may be given in a single or multiple doses daily. In a preferred embodiment, the pharmaceutical compositions including the benzoyl peroxide pad compositions and the flowable compositions, are each given from one to three times daily. Starting with a low dose twice daily and slowly working up to higher doses if needed is a preferred strategy. The amount of active ingredients that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated, the nature of the disease, disorder, or condition, and the nature of the active ingredients.

[176] It is understood, however, that a specific dose level for any particular patient will depend upon a variety of factors well known in the art, including the activity of the active ingredients, i.e., benzoyl peroxide, in the patient's body; the age, body weight, general health, sex and diet of the patient; the time of administration; the rate of excretion; drug combination; the severity of the acne being treated; and the form of administration. One of ordinary skill in the art would appreciate the variability of such factors and would be able to establish specific dose levels using no more than routine experimentation.

[177] The optimal pharmaceutical formulations will be determined by one skilled in the art depending upon considerations such as the particular drug or drug combination and the desired dosage. See, for example, Remington's Pharmaceutical Sciences. 18th ed. (1990, Mack Publishing Co., Easton, PA 18042), pp. 1435-1712, the disclosure of which is hereby incorporated by reference in its entirety. Such formulations may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the therapeutic agents.

Package [178] The present subject matter is further directed to a package comprising an outer container; and a first product container and a second product container within the outer container, wherein the first product container contains at least one pad containing a drug composition absorbed thereon, said drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80-90% by weight water, and about 0.1-1.5% by weight of a surfactant system; and said second product container contains a flowable composition of one or more agents suitable for the treatment of acne. [179] The package of the present subject matter comprises an outer container. The outer container can be any container suitable for holding within the first product container and the second product container. One non-limiting example of a suitable outer container is a carton. In this example, the carton is large enough to contain the first product container and the second product container within its confines. The carton may be made of any suitable material that provides the structural support for holding the first product container and the second product container. Materials useful as the carton include, without limitation, cardboard, paper, metal and plastic. [180] In an alternative embodiment, the outer container comprises shrink-wrap. In this embodiment, the first product container and the second product container are placed in close proximity with one another and shrink wrap is placed around the product containers, thereby physically binding the containers to each other. [181] The present packaging also contemplates a divider being placed between the first product container and the second product container within the outer container. The divider physically separates the product containers, and may be present whether the outer container is a carton or shrink wrap. Materials useful as the divider include, without limitation, cardboard, paper, metal and plastic. [182] The outer container of the present packaging also contains an item selected from the group consisting of a single bar code, a single new drug code and a single universal product code. Since the first product container and the second product container preferably contain distinct compositions, it is possible that the product containers may be separated from the outer container prior to purchase by a user, and the separate product containers may then be offered for individual sale. The presence of a single bar code, new drug code and/or universal product code on the outside of the outer container will help make the individual sale of the product containers more difficult.

[183] The present subject matter also contemplates that the package will contain one or more additional product containers within the outer container. The one or more additional product containers preferably contain a composition distinct from the flowable composition, for example, a soap-free cleanser and/or a barrier repair composition, as well as an additional cleanser. The one or more additional product containers can comprise a container containing a barrier repair composition or an additional cleanser.

EXAMPLES

[184] The following examples are illustrative of preferred compositions and are not intended to be limitations thereon. All polymer molecular weights are mean average molecular weights. All percentages are based on the percent by weight of the final delivery system or formulation prepared unless otherwise indicated and all totals equal 100% by weight.

EXAMPLE 1

[185] The following example illustrates the preparation of preferred benzoyl peroxide pads of the present subject matter. The pads have absorbed thereon a 4% benzoyl peroxide composition comprising:

% W/W

Purified Water 88.71

Carbomer 940, NF 0.50

Poloxamer 182 0.20

Benzoyl peroxide (75%), USP 6.13

Glycerin, USP 4.00

Methylparaben, NF 0.04

Disodium lauryl sulfosuccinate 0.04

Silicon dioxide, NF 0.25

Edetate disodium 0.10 Sodium Hydroxide 0.03

100.0% [186] Preparation of the benzoyl peroxide composition and benzoyl peroxide pads:

1 ) Adding 829.6 kg of water to a suitable vessel and heating the water to about 7O⁰C;

2) Adding 5.0 kg of Carbomer 940 to the water and mixing the Carbomer/water mixture for about 15 minutes, or until the Carbomer is suitably hyd rated;

3) Adding successively 2.0 kg of poloxamer 182, 40.0 kg of glycerin, 0.4 kg of methylparaben, 2.5 kg of silicon dioxide, 0.4 kg of disodium lauryl sulfosuccinate, and 1.0 kg of edentate disodium to the carbomer mixture;

4) Cooling the above mixture to a temperature of about 20-25⁰C while maintaining mixing of the mixture;

5) In a further vessel, adding 3.0 kg of water and 0.3 kg of sodium hydroxide;

6) Adding the sodium hydroxide solution to the further mixture from step 4) and mixing for 10 minutes;

7) In a separate vessel, adding 125.0 kg of the mixture from step 6) with 70.8 kg of water and 46.0 kg of benzoyl peroxide and milling the resultant mixture to reduce particle size to no greater than 60 microns;

8) Adding 40.0 kg of water to the mixture from step 7) and mixing for 30 minutes;

9) Adjusting the pH of the mixture to at least a pH of 5.5 by adding sodium hydroxide solution to the mixture from step 8);

10) Adding the remaining water and mixing for 5 minutes; 11 ) Absorbing the mixture from step 10) onto and into suitable pads.

EXAMPLE 2

[187] The following example illustrates the preparation of preferred benzoyl peroxide pads of the present subject matter. The pads have absorbed thereon a 4% benzoyl peroxide composition comprising:

% W/W

Purified Water 88.72

Carbomer 940, NF 0.30

Poloxamer 182 0.20

Benzoyl peroxide (75%), USP 6.20

Glycerin, USP 4.00

Methylparaben, NF 0.10

Disodium lauryl sulfosuccinate 0.10

Hydrated Silica 0.25

Disodium EDTA 0.10

Sodium Hydroxide 0.03

100.0%

[188] This benzoyl peroxide composition was prepared according to the procedure set forth above with respect to Example 1. This benzoyl peroxide composition was then absorbed onto and into suitable pads to produce the present benzoyl peroxide pads.

EXAMPLE 3

[189] The following example illustrates the preparation of preferred benzoyl peroxide pads of the present subject matter. The pads have absorbed thereon a 4% benzoyl peroxide composition comprising: % W/W

Purified Water 88.85

Carbomer 940, NF 0.30

Poloxamer 182 0.20

Benzoyl peroxide (75%), USP 6.13

Glycerin, USP 4.00

Methylparaben, NF 0.10

Disodium lauryl sulfosuccinate 0.04

Silicon dioxide, NF 0.25

Edetate disodium 0.10

Sodium Hydroxide 0.03

100.0%

[190] This benzoyl peroxide composition was prepared according to the procedure set forth above with respect to Example 1. This benzoyl peroxide composition was then absorbed onto and into suitable pads to produce the present benzoyl peroxide pads.

EXAMPLE 4

[191] The following example illustrates the preparation of preferred benzoyl peroxide pads of the present subject matter. The pads have absorbed thereon a 8% benzoyl peroxide composition comprising:

% W/W

Purified Water 82.54

Carbomer 940, NF 0.50

Poloxamer 182 0.20

Benzoyl peroxide (75%), USP 12.30 Glycerin, USP 4.00

Methylparaben, NF 0.04

Disodium lauryl sulfosuccinate 0.04

Silicon dioxide 0.25

Disodium EDTA 0.10

Sodium Hydroxide 0.03

100.0%

[192] This benzoyl peroxide composition was prepared according to the procedure set forth above with respect to Example 1. This benzoyl peroxide composition was then absorbed onto and into suitable pads to produce the present benzoyl peroxide pads.

EXAMPLE 5

[193] The following example illustrates the preparation of a preferred benzoyl peroxide wash of the present subject matter. The benzoyl peroxide wash comprises:

% W/W

Benzoyl Peroxide Hydrous 5.87

Dimethyl lsosorbide 0.10

Glycolic Acid 0.35 lmidurea 0.50

Methylparaben 0.10

Purified Water 50.22

Sodium Hydroxide 0.10

Sodium Pyrollidone Carboxylate 1.00

Tensianol 399 KS-1 41.76

100.0% [194] The benzoyl peroxide wash according to the described subject matter was prepared by the following procedure. The water was placed into a suitable vessel and heated to between 6O⁰C and 7O⁰C. The synthetic surfactant (Tensianol 399 KS- 1 ) was added to the water while the water was stirred. The resultant solution was then allowed to cool. While the solution was cooling, the glycolic acid, dimethyl isosorbide, and sodium pyrollidone carboxylate were added to the solution while stirring was continued. When the temperature of the solution fell to between 25⁰C and 35⁰C, the imidurea, methylparaben and benzoyl peroxide were added to the solution, and stirring was continued. The resultant suspension was mixed and passed through a Gaulin Homogenizer until a smooth product with a mean particulate particle size of less than 60 microns was obtained. The pH of the product was then adjusted with sodium hydroxide to a pH of 3-5.

[195] Tensianol 399 KS-1 , which is available from Uniqema, Inc., Wilmington, Del. contains cetostearyl alcohol, cocamidopropyl betaine, corn starch, glycerin, hydrogenated castor oil, mineral oil, PEG-14M, sodium potassium lauryl sulfate, and titanium dioxide

EXAMPLE 6

[196] The following example illustrates the preparation of a preferred benzoyl peroxide wash of the present subject matter. The benzoyl peroxide wash was prepared in accordance with the method as set forth in Example 5. The benzoyl peroxide wash comprises:

% W/W

Benzoyl Peroxide Hydrous 2.50

Dimethyl Isosorbide 0.10

Glycolic Acid 2.00 lmidurea 0.50

Methylparaben 0.10

Purified Water 39.80

Sodium Hydroxide q.s. to pH of 3-5

Sodium Pyrollidone Carboxylate 10.00

Tensianol 399 KS-1 45.00

100.0%

EXAMPLE 7

[197] The following example illustrates the preparation of a preferred benzoyl peroxide wash of the present subject matter. The benzoyl peroxide wash was prepared in accordance with the method as set forth in Example 5, with the lactic acid being added at the same time as the glycolic acid. The benzoyl peroxide wash comprises:

% W/W

Benzoyl Peroxide Hydrous 5.00

Dimethyl lsosorbide 1.00

Glycolic Acid 1.00

Lactic Acid 1.00 lmidurea 0.50

Methylparaben 0.10

Purified Water 53.40

Sodium Hydroxide q.s. to pH of 3-5

Sodium Pyrollidone Carboxylate 3.00

Tensianol 399 KS-1 35.00

100.0% EXAMPLE 8

[198] The following example illustrates the preparation of a preferred benzoyl peroxide wash of the present subject matter. The benzoyl peroxide wash was prepared in accordance with the method as set forth in Example 5, with the lactic acid being added at the time when the glycolic acid was added. The benzoyl peroxide wash comprises:

% W/W

Benzoyl Peroxide Hydrous 7.50

Dimethyl lsosorbide 5.00

Lactic Acid 5.00 lmidurea 0.50

Methylparaben 0.10

Purified Water 39.40

Sodium Hydroxide q.s. to pH of 3-5

Sodium Pyrollidone Carboxylate 5.00

Tensianol 399 KS-1 37.50

100.0% EXAMPLE 9

[199] The following example illustrates the preparation of a preferred benzoyl peroxide wash of the present subject matter. The benzoyl peroxide wash was prepared in accordance with the method as set forth in Example 5, with the lactic acid being added at the time when the glycolic acid was added. The benzoyl peroxide wash comprises:

% W/W Benzoyl Peroxide Hydrous 10.00 Dimethyl lsosorbide 10.00

Lactic Acid 10.00 lmidurea 0.50

Methylparaben 0.10

Purified Water 37.40

Sodium Hydroxide q.s. to pH of 3-5

Sodium Pyrollidone Carboxylate 2.00

Tensianol 399 KS-1 30.00 100.0%

Table 1A poo] Table 1A shows the stability data for a 254.1 Kg batch of a benzoyl peroxide wash of the present subject matter. The initial amount of benzoyl peroxide present in the treatment was 4.66%. Samples were tested from the BOTTOM of the batch.

Table 1 B

[201] Table 1 B shows the stability data for a 254.1 Kg batch of the wash composition shown in Table 1A. Samples were tested from the TOP of the batch.

[202] As shown in Tables 1A and 1B, a benzoyl peroxide wash according to the invention having an initial amount of benzoyl peroxide of about 4.5% showed good stability with respect to the benzoyl peroxide component at temperatures of 25⁰C and 3O⁰C for at least about 182 days. At 4O⁰C the composition showed acceptable stability (i.e., at least about 90% of the initial amount of benzoyl peroxide) for 30 days, but significant degradation (i.e., more than about 10%) when maintained at 4O⁰C for 60 days or more.

Table 2A

[203] Table 2A shows the stability data for a 253.5 Kg batch of a benzoyl peroxide wash of the present subject matter. The initial amount of benzoyl peroxide present in the wash was 9.04%. Samples were tested from the BOTTOM of the batch.

Table 2B

[204] Table 2B shows the stability data for a 253.5 Kg batch of the composition shown in Table 2A. Samples were tested from the TOP of the batch.

[205] As shown in Tables 2A and 2B, a benzoyl peroxide wash according to the invention having initial amount of benzoyl peroxide of about 9.0% showed good stability with respect to the benzoyl peroxide component at temperatures of 25⁰C and 3O⁰C for at least about days. At 4O⁰C the composition showed acceptable stability for at least 60 days, but significant degradation when maintained at 4O⁰C for 90 days or more.

EXAMPLE 10 [206] The following example illustrates the preparation of a soap-free cleanser of the present subject matter. The soap-free cleanser comprises:

% W/W

Purified Water 91.50

Polyethylene Glycol 3350NF 5.00

Sodium Cocoyl lsethionate 0.70

Methylparaben, NF 0.20

Stearyl Alcohol 2.50

Propylparaben, NF 0.05

Butylparaben, NF 0.05

100.0%

[207] The soap-free cleanser was prepared by adding 3020 kg of purified water to a suitable vessel. The water was heated under stirring to a temperature of 72±2°C within 55 to 180 minutes. As the stirring continued, 165 kg of polyethylene glycol 3350, NF₁ 23.1 kg of sodium cocoly isethionate, and 6.6 kg of methylparaben, NF were added to the heated water. The mixture was mixed for 20 minutes while maintaining the temperature. In a separate vessel, 82.5 kg of stearyl alcohol, 1.65 kg of propylparaben and 1.65 kg of butyl paraben are mixed and heated to 72±2°C within 45 to 85 minutes until all ingredients have melted and a uniform appearance is produced. While continually stirring, the mixture from the second vessel is slowly added to the mixture of the first vessel. The combined mixtures are stirred for 10 minutes while the temperature is maintained at 72±2°C. While continuous stirring, the composition is cooled to a temperature of 32±2°C within 135 to 155 minutes. The cooled composition is then properly packaged.

EXAMPLE 11 [208] The following example illustrates the preparation of an alternative preferred soap-free cleanser of the present subject matter. The soap-free cleanser was prepared in accordance with the method as set forth in Example 10. The soap-free cleanser comprises:

% W/W

Purified Water 90.70

Polyethylene Glycol 3350 5.00

Sodium Cocoyl lsethionate 1.50

Methylparaben, NF 0.20

Stearyl Alcohol 2.50

Propylparaben, NF 0.05

Butylparaben, NF 0.05

100.0%

EXAMPLE 12

[209] The following example illustrates the preparation of an alternative preferred soap-free cleanser of the present subject matter. The soap-free cleanser was prepared in accordance with the method as set forth in Example 10. The soap-free cleanser comprises:

% W/W

Purified Water 82.25

Polyethylene Glycol 78 Glyceryl Cocoate 10.00

Laneth-16 1.00

Cocamphopropionate 5.00

Benzyl Alcohol 1.00

Acetamide MEA 0.75

Sodium Hydroxide q.s. pH about 5.5 100.0%

EXAMPLE 13

[210] The following example illustrates the preparation of an alternative preferred soap-free cleanser of the present subject matter. The soap-free cleanser was prepared in accordance with the method as set forth in Example 10. The soap-free cleanser comprises:

% W/W

Purified Water 81.25

Polyethylene Glycol 3350 5.00

Propylene Glycol 5.00

Glycerin 8.00

Sodium Methyl Cocoyl Taurate 0.75

100.0%

EXAMPLE 14

[211] The following example illustrates the preparation of an alternative preferred soap-free cleanser of the present subject matter. The soap-free cleanser was prepared in accordance with the method as set forth in Example 10. The soap-free cleanser comprises:

% VWW

Purified Water 93.10

Cetyl Alcohol 2.50

Sorbitol 2.00

Stearyl Alcohol 2.00

Sodium Lauryl Sulfate 0.30

Methylparaben 0.05 Propylparaben 0.05

100.0% EXAMPLE 15

[212] An additional cleanser according to the present subject matter is prepared to assess its effects on one or more dermatological conditions. The composition is in the form of a bar and comprises the following ingredients:

Table 3

Synthetic Surfactants 3-30%

Processing aids (e.g., acid salts, silicate, silica) 0.01-10% Emollients (e.g., fatty alcohols, glycerin, vegetable and/or mineral oils) 1-10% Coloring agents and dyes q.s.

Keratolytic agents (e.g., alpha or beta hydroxy acids) 0.5-10% Thickeners 0.025-5%

Active ingredients (e.g., benzoyl peroxide) 0-20% Water q.s. Preservatives q.s.

EXAMPLE 16

An additional cleanser according to the present subject matter is prepared to assess its effects on one or more dermatological conditions. The composition is in the form of a bar and comprises the following ingredients:

Table 4

Sythetic Surfactants (e.g., cocamidopropyl betaine, sodium lauryl sulfate, potassium lauryl sulfate) 3-30%

Processing aids (e.g., Polymers, Sodium silicate, Sodium sulfate, potassium phosphate, silica) 0.01-10% Emollients (e.g., cetearyl alcohol, glycerin, hydrogenated castor oil, mineral oil) 1-

10%

Coloring agents and dyes (e.g., titanium dioxide, optical brighteners) q.s.

Keratolytic agents (e.g., lactic acid) 0.5-10%

Thickeners (e.g., corn starch) 0.025-5%

Active ingredients (e.g., benzoyl peroxide) 0-20%

Water q.s.

Preservatives q.s.

EXAMPLE 17

[213] The following example illustrates the preparation of an alternative preferred soap-free cleanser of the present subject matter. The soap-free cleanser was prepared in accordance with the method as set forth in Example 10. The soap-free cleanser comprises:

% W/W

Purified Water 88.05

Cetyl Alcohol 2.50

Stearyl Alcohol 2.50

Glycerin 5.00

Sodium Lauryl Sulfate 0.25

Benzyl Alcohol 1.50

Citric Acid 0.20

Sodium Hydroxide q.s. pH about 5.5

100.0% EXAMPLE 18 [214] Example 18 describes a barrier repair composition cream formulation for extremely stressed aged skin. The barrier repair composition comprises:

Phase 1 Amount hydrogenated phosphatidylcholine, concentration of 2.0 g hydrogenated phosphatidylcholine 90% by weight monoglyceride C 12 1.5 g olive oil 17.1 O g cholesterol 2.0 g ceramide 3 0.1 g avocadine 1.0 g squalene 1.0 g pentylene glycol 5.0 g palmitic acid 1.0 g Phase 2 acetamide MEA 0.5 g betaine, water-free 0.8 g carnitine 0.5 g water DAB 10 ad 100.0 g pis] Phase 1 and Phase 2 were first heated to 75°C. Then Phase 2 was slowly added to Phase 1 while the temperature was maintained and the mixture was continuously stirred. After a complete mixture was prepared it was then homogenized for two minutes at 15000 rpm using a homogenizer (Ultra Turrax). This homogenizing was followed by forced homogenizing by means of high-pressure homogenisation lasting five minutes at 790 bar. The mixture was then cooled to 37°C with continuous stirring. The mixture was then homogenized again for three minutes using an Ultra Turrax homogenizer at 8000 rpm. After this the mixture was cooled to room temperature with continuous stirring.

EXAMPLE 19

[216] A patient is suffering from acne. The benzoyl peroxide pad of Example 1 is topically administered to the patient. Thereafter, the flowable composition of Example 5 is administered to the patient. It would be expected that the patient would improve his/her condition or recover.

EXAMPLE 20

[217] A patient is suffering from acne. The benzoyl peroxide pad of Example 2 is topically administered to the patient. Thereafter, the flowable composition of Example 5 is administered to the patient. It would be expected that the patient would improve his/her condition or recover.

EXAMPLE 21

[218] A patient is suffering from acne. The flowable composition of Example 5 is administered to the patient. The benzoyl peroxide pad of Example 2 is then topically administered to the patient. It would be expected that the patient would improve his/her condition or recover.

EXAMPLE 22

[219] A patient is suffering from acne. The flowable composition of Example 6 is administered to the patient. The benzoyl peroxide pad of Example 1 is then topically administered to the patient. It would be expected that the patient would improve his/her condition or recover.

EXAMPLE 23

[220] A patient is suffering from acne. The flowable composition of Example 6 is administered to the patient. The benzoyl peroxide pad of Example 1 is then topically administered to the patient. Thereafter, the barrier repair composition of Example 10 is administered to the patient. It would be expected that the patient would improve his/her condition or recover.

EXAMPLE 24

[221] A patient is suffering from acne. The additional cleanser of Example 15 is topically administered to the patient. The benzoyl peroxide pad of Example 1 is further topically administered to the patient. Thereafter, the barrier repair composition of Example 10 is administered to the patient. It would be expected that the patient would improve his/her condition or recover.

[222] The present subject matter being thus described, it will be apparent that the same may be modified or varied in many ways. Such modifications and variations are not to be regarded as a departure from the spirit and scope of the present subject matter, and all such modifications and variations are intended to be included within the scope of the following claims.

Claims

WE CLAIM:

1. A kit comprising: a) at least one pad containing a drug composition absorbed thereon, said drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80- 90% by weight water, and about 0.1-1.5% by weight of a surfactant system; and b) a container containing a flowable composition of one or more agents suitable for the treatment of acne.

2. The kit according to claim 1 wherein said flowable composition comprises about 2-20% by weight benzoyl peroxide.

3. The kit according to claim 1 wherein said surfactant system comprises about 50-95% by weight of at least one nonionic surfactant and about 5-50% by weight of at least one anionic surfactant.

4. The kit according to claim 3 wherein said at least one nonionic surfactant is selected from the group consisting of alkanolamides, amine oxides, esterified carboxylic acids, ethoxylated alcohols, poloxamers, and mixtures thereof.

5. The kit according to claim 4 wherein said at least one nonionic surfactant is a poloxamer.

6. The kit according to claim 3 wherein said at least one anionic surfactant is selected from the group consisting of carboxylates, amino acid derivatives, alkyl sulphates, alkyl ether sulfates, sulphonates, isethionates, taurates, sulfosuccinates, alkyl sulfoacetates, phosphates, alkyl phosphates, and mixtures thereof.

7. The kit according to claim 5 wherein said at least one anionic surfactant is disodium lauryl sulfosuccinate.

8. The kit according to claim 3 wherein said at least one nonionic surfactant is a poloxamer and said at least one anionic surfactant is disodium lauryl sulfosuccinate.

9. The kit according to claim 1 wherein said kit comprises at least one additional composition.

10. The kit according to claim 9 wherein said at least one additional composition is selected from the group consisting of a soap-free cleanser, a barrier repair composition, and combinations thereof.

11. The kit according to claim 1 wherein said drug composition and said flowable composition each have a pH from 2 to 7.

12. The kit according to claim 1 wherein the benzoyl peroxide in the drug composition has a particle size of less than about 60 microns.

13. The kit according to claim 1 wherein said at least one pad is individually packaged.

14. The kit according to claim 1 wherein the kit comprises a registered device, wherein the registered device is a barrier repair composition.

15. The kit according to claim 1 wherein the flowable composition produces more foam than the drug composition.

16. A method for treating acne comprising administering to a patient in need thereof a combination of products comprising: a) a first product comprising at least one pad containing a drug composition absorbed thereon, said drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80- 90% by weight water, and about 0.1-1.5% by weight of a surfactant system; and b) a second product comprising a container containing a flowable composition of one or more agents suitable for the treatment of acne.

17. The method according to claim 16 wherein one of said first product and said second product is administered in the morning and the other is administered at night.

18. The method according to claim 16 wherein said first product and said second product are administered sequentially.

19. The method according to claim 16 wherein said first product and said second product are administered intermittently.

20. The method according to claim 16 wherein said flowable composition cleanses the skin of a user to which it is applied.

21. The method according to claim 20 wherein said cleansing potentiates effectiveness of said drug composition.

22. The method according to claim 20 wherein said cleansing reduces dirt, exfoliates, reduces excess sebum, and/or reduces microbial count in the skin of the user.

23. The method according to claim 20, further comprising administering a third product comprising a soap-free cleanser to aid in cleansing the skin.

24. The method according to claim 16 wherein the drug composition and the flowable composition synergistically treat acne.

25. The method according to claim 16 further comprising a final step of administering a barrier repair composition.

26. The method according to claim 25 wherein the barrier repair composition repairs any damage to the skin.

27. A package comprising: an outer container; and a first product container and a second product container within the outer container, wherein the first product container contains at least one pad containing a drug composition absorbed thereon, said drug composition comprising about 2.5-13% by weight benzoyl peroxide, about 80- 90% by weight water, and about 0.10-1.5% by weight of a surfactant system; and said second product container contains a flowable composition of one or more agents suitable for the treatment of acne.

28. The package according to claim 27 wherein the outer container is a carton.

29. The package according to claim 27 wherein the outer container is shrink- wrap.

30. The package according to claim 27 further comprising a divider between said first container and said second container.

31. The package according to claim 27 wherein the outer container contains an item selected from the group consisting of a single bar code, a single new drug code and a single universal product code.

32. The package according to claim 27 wherein the package further comprises one or more additional product containers within the outer container.

33. The package according to claim 32 wherein the one or more additional product containers contains a barrier repair composition.

34. The package according to claim 27 wherein said first container and said second container are unit dose containers.

35. The method according to claim 16, wherein the flowable composition comprises a benzoyl peroxide wash composition.

36. The method according to claim 35, wherein the benzoyl peroxide wash composition comprises benzoyl peroxide, a synthetic surfactant and a moisturizer.

37. The method according to claim 35, wherein the benzoyl peroxide wash composition comprises benzoyl peroxide in an amount of from about 1 % to about 20% by weight of the benzoyl peroxide wash composition.

38. The method according to claim 35, wherein the benzoyl peroxide wash composition comprises a moisturizer in an amount of from about 1% to about 15% by weight of the benzoyl peroxide wash composition.

39. The method of claim 35, wherein administering the benzoyl peroxide wash composition comprises topically administering the benzoyl peroxide wash composition to an affected area and maintaining the benzoyl peroxide wash composition in contact with the affected area for about 15 seconds to about 30 minutes before removing the benzoyl peroxide wash composition from the affected area.

40. The method of claim 35, wherein administering the benzoyl peroxide wash composition comprises topically administering the benzoyl peroxide wash composition to an affected area and maintaining the benzoyl peroxide wash composition in contact with the affected area for about 15 seconds to about 120 seconds before removing the benzoyl peroxide wash composition from the affected area.

41. The method according to claim 23, wherein administering a soap-free cleanser comprises topically administering the soap-free cleanser to an affected area and maintaining the soap-free cleanser in contact with the affected area for about 15 seconds to about 30 minutes before removing the soap-free cleanser from the affected area.

42. The method according to claim 23, wherein administering a soap-free cleanser comprises topically administering the soap-free cleanser to an affected area and maintaining the soap-free cleanser in contact with the affected area for about 15 seconds to about 120 seconds before removing the soap-free cleanser from the affected area.

43. The package according to claim 27, wherein the flowable composition comprises a benzoyl peroxide wash composition.

44. The package according to claim 43, further comprising instructions comprising indicia instructing a patient to topically administer the benzoyl peroxide wash composition to an affected area and maintain the benzoyl peroxide wash composition in contact with the affected area for about 15 seconds to about 30 minutes before removing the benzoyl peroxide wash composition from the affected area.

45. The package according to claim 43, further comprising instructions comprising indicia instructing a patient to topically administer the benzoyl peroxide wash composition to an affected area and maintain the benzoyl peroxide wash composition in contact with the affected area for about 15 seconds to about 120 seconds before removing the benzoyl peroxide wash composition from the affected area.

46. The package according to claim 27, further comprising a third product container disposed within the outer container, the third product container comprising a soap-free cleanser.

47. The package according to claim 46, further comprising instructions comprising indicia instructing a patient to topically administer the soap-free cleanser to an affected area and maintain the soap-free cleanser in contact with the affected area for about 15 seconds to about 30 minutes before removing the soap-free cleanser from the affected area.

48. The package according to claim 43, further comprising instructions comprising indicia instructing a patient to topically administer the soap-free cleanser to an affected area and maintain the soap-free cleanser in contact with the affected area for about 15 seconds to about 120 seconds before removing the soap-free cleanser from the affected area.