MXPA06009922A - Film products having controlled disintegration properties - Google Patents

Abstract

This invention relates generally to films having barrier as well as controlled disintegration properties and, more particularly, to controlled water disintegratable films.

Description

FILM PRODUCTS THAT HAVE PROPERTIES OF CONTROLLED DISGREGATION This continuation application in part claims the benefit of United States Patent Application No. 10 / 792,362, filed March 3, 2004, the entirety of which is hereby incorporated by reference as if fully indicated herein. This invention relates in general to films having barrier properties as well as controlled disintegration and, more particularly, to water-controlled disintegration films.

BACKGROUND OF THE INVENTION A variety of topical application products are known in the art, including strips, films, patches and the like. Such products are particularly useful when a protective film is recommended or when drug or medication retention is desirable. Protective films are particularly desirable in situations where wounds or surface openings are present and should be protected. Alternatively, when a drug or medication is easily removed by washing or cleaning the application area (e.g., transdermal applications), mechanical retention of the drug or medication becomes particularly desirable.

More recently, strip or film products have enjoyed a renewed popularity in the field of oral hygiene. Particular interest has been given to the areas of teeth whitening and oral transdermal delivery of drugs and medications. Although a variety of strip or film type products have been disclosed, there remains a need for improved film or film-type compositions that are easier to use and reduce the inconvenience or discomfort typically associated with the joining of such foreign objects. to sensitive parts of the body. A disadvantage observed with respect to the aforementioned film or strip products refers to the need to eventually remove by peeling or otherwise remove and dispose of the film or strip product after delivery of the topical or systemic active substance. In facing this disadvantage, the inventors of this Invention have discovered that film compositions comprising selected water-insoluble polymers and disintegration enhancer selected from the group consisting of a plasticizer, a water-insoluble particulate material or mixtures thereof provide film compositions having good protective properties as well as Improved disintegration properties. Accordingly, it is an aspect of the present invention to provide improved film products having protective properties, such that the film prevents foreign substances, chemicals or active substances from crossing from one side of the film to the other. It is another aspect of the present invention to provide film products having controlled disintegration or dissolution properties (or extended or extended type) in aqueous environments. It is yet another aspect of the present invention to provide film products for delivering topical or systemic active substances. It is yet another aspect of the present invention to provide film products for delivering topical or systemic active substances in which the film disintegrates after 60 minutes, optionally after 45 minutes, optionally after 30 minutes or, optionally, at After 15 minutes in a watery environment.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to film compositions comprising at least one water-insoluble polymer, a disintegration enhancer selected from the group consisting of a plasticizer, a water-insoluble particulate material or mixtures thereof, and optionally at least one substance active topical or systemic, in which the film is partial, substantial or completely disintegrable in an aqueous environment. The film composition of the present invention can be used as a monolayer film or together with one or more additional film layers to form a bi-layer or multilayer film product. In a modality, the film of the present invention may be in the form of a monolayer film comprising an adhesive composition, the adhesive composition comprising an adhesive substance and a topical or systemic active substance. The film is then applied to the teeth, mucosa or other affected area of the skin or mouth and allowed to disintegrate over time in the presence of oral fluids or other aqueous media. In another embodiment, the film of the present invention forms the first layer or support layer of a bilayer film, the second layer being a water soluble polymeric film such as that described in U.S. Pat. 6,596,298 to Leung et al. and 6,419,903 to Xu et al., both of which are incorporated herein by reference in their entirety. The bilayer film is then applied to the teeth, oral mucosa or other affected area of the skin or mouth and allowed to disintegrate over time in the presence of oral fluids or other aqueous media. Similarly, the film of the present invention can be incorporated into multilayer films and used as above to achieve the benefits of the present invention. Methods of using the above film compositions are also disclosed.

DETAILED DESCRIPTION OF THE PRESENT INVENTION The film compositions of the present invention may comprise, consist of or consist essentially of the essential elements and limitations of the invention described herein, as well as any of the additional or optional ingredients, components or limitations described herein. All percentages, parts and ratios are based on the total weight of the wet film composition of the present invention, unless otherwise specified. All such weights, when referring to the ingredients listed, are based on the active level and, therefore, do not include vehicles or by-products that may be included in commercially available materials, unless otherwise specified. The term "safe and effective amount", as used herein, means an amount of a compound or composition such as a topical or systemic active substance sufficient to significantly induce a positive benefit, for example a teeth whitening, an antimicrobial benefit. and / or analgesic, independently including the benefits disclosed herein, but sufficiently low to avoid serious side effects, specifically to provide a reasonable ratio of benefit to risk, within the reach of the formal criteria of the person skilled in the art. The term "adhesive", as used herein, means any material or composition that is capable of sticking to the site of application or topical administration and includes, but is not limited to, mucoadhesives, pressure sensitive adhesives (adhere after application) of pressure), wettable adhesives (adhere in the presence of water) and sticky or adhesive type adhesives (adhere after immediate contact with a surface). The term "foreign substances", as used herein, means dirt, infectious microorganisms and the like. Optionally, the film compositions of the present invention are transparent. The term "transparent", as defined herein, is in the range of transparent to translucent observed with the naked eye. The film compositions of the present invention, including the essential and optional components thereof, are described in detail hereinafter.

The water-insoluble polymer The film compositions of the present invention comprise water-insoluble polymers. Suitable water insoluble polymers include, but are not limited to, hydrogenated vegetable oils; natural rosins such as wood rosins and rubber rosins; vegetable proteins such as corn protein, pea protein or soy protein; hydrogenated castor oil; polyvinylchloride); shellac; polyurethane; cellulose derivatives such as cellulose or ethyl cellulose; waxes; polymers such as those marketed under the trademark Eudragit RS or a mixture thereof. Hydrogenated vegetable oils suitable for use herein include, but are not limited to, hydrogenated forms of safflower oil, castor oil, coconut oil, cottonseed oil, canola oil, oil of tyroleaus, seed oil palm, palm oil, peanut oil, soybean oil, rape seed oil, flax seed oil, rice bran oil, pine oil, sesame oil, sunflower seed oil, hydrogenated safflower oil and mixtures thereof. Examples of waxes suitable for use herein include, but are not limited to, paraffin wax, carnauba wax, candelilla wax, sugar cane wax, beeswax, cetyl ester wax, Montana wax, glycerin, castor wax, wax whale sperm, shellac wax, microcrystalline wax, petrolatum and mixtures thereof. The Eudragit polymers are lacquer polymeric substances based on acrylate and methacrylate. The polymers marketed under the trademark Eudragit RL and RS are resins comprising copolymers of esters of acrylic and methacrylic acid with a low content of quaternary ammonium groups., and are described in the brochure "Eudragit" of Rohm Pharma GmbH (1982), in which detailed physicochemical data of these products are given. The ammonium groups are present in the form of salts and give rise to the permeability of the lacquer films. Eudragit RL and RS are freely permeable (RL) or slightly permeable (RS), respectively, regardless of the pH. Additional water-insoluble polymers are detailed in U.S. Pat. 6,183,777; 4,721, 619 and 6,251, 427, each of which is incorporated herein by reference in its entirety. Mixtures of any of the above ingredients can also be used. In certain embodiments, the water insoluble polymer may include shellac marketed under the trade name Pharmaceutical Glaze and supplied by Mantrose Haeser Co., Attleboro, Ma. When incorporated into the film compositions of the present invention, the water insoluble polymer it is present at a concentration of from about 10% to about 80%, optionally from about 15% to about 40%, and optionally from about 20% to about 35% by weight of the wet film composition.

The breakdown enhancer Plasticizers or Plasticizing Agents The film compositions of the present invention also comprise at least one disintegration enhancer selected from the group consisting of plasticizers or plasticizers, water-insoluble particles or mixtures thereof. Examples of suitable plasticizers include, but are not limited to, alkyl esters of citric acid, glycerol esters such as glycerol monooleate and glycerol monostearate, alkyl esters of phthalic acid, alkyl esters of sebacic acid, sucrose esters, sorbitan esters , acetylated monoglycerides, glycerols, fatty acid esters, glycols, propylene glycol and polyethylene glycols 200 to 12,000 and mixtures thereof. Specific plasticizers include, but are not limited to, lauric acid, sucrose, sorbitol, triethyl citrate, acetyltriethyl citrate, triacetin (glyceryl triacetate), poloxamers, alkylaryl phosphates, diethyl phthalate, tributyl citrate, dibutyl phthalate, dibutyl sebacate, polysorbate, the Carbwax® series of polyethylene glycols (Union Carbide Corporation) and mixtures thereof. In certain embodiments, the plasticizers may include mono- and diglycerides of edible fats or oils supplied by Lonza Inc., Fair Lawn, NJ or Eastman's triacetin (food purity) supplied by Eastman Chemical Company, Kingsport, TN. When incorporated into the film compositions of the present invention, the plasticizer is present at a concentration of from about 0.1% to about 10%, preferably from about 0.1% to about 5%, most preferably from about 0.5% to about 1.5% by weight of the wet film composition.

Water-insoluble particles The disintegration enhancer can also be a water-insoluble particle. Various types of organic powders and inorganic powders can be used as water insoluble particles. Inorganic powders which are useful herein include, but are not limited to, microfine particles or granules of alumina, talc, magnesium stearate, titanium dioxide, barium titanate, magnesium titanate, calcium titanate, strontium titanate, zinc, silica sand, clay, mica, wollastonite, diatomaceous earth, various inorganic oxide pigments, chromium oxide, cerium oxide, iron red, antimony trioxide, magnesium oxide, zirconium oxide, barium sulfate, carbonate barium, calcium carbonate, silica (colloidal or fuming), silicon carbide, silicon nitride, boron carbide, tungsten carbide, titanium carbide, carbon black and mixtures thereof. The organic powders which are useful in the present invention include, for example, crosslinked and non-crosslinked polymer powders, organic pigments, charge control agents and waxes. Crosslinked and non-crosslinked powder resins include, but are not limited to, for example styrene type acrylic resin, acrylic type, methacrylic type, polyethylene type, polypropylene type, silicone type, polyester type, polyurethane type , of the polyamide type, epoxy type, polyvinyl butyral type, rosin type, terpene type, phenol type, melamine type and guanamine type. Mixtures of any of the above organic or inorganic powders can also be used. Additional particles useful in the present invention can be found in U.S. Pat. 6,475,500, 5,611, 885 and 4,847,199, each of which is incorporated herein by reference in its entirety. The water-insoluble particles of the present invention generally have a particle size of less than 10 microns, optionally from about 0.01 microns to about 5 microns, optionally from about 0.1 microns to about 1 microns, and optionally from about 0.1 to about 0.5 microns. . In certain modalities, insoluble particles may include Cabosil M-5 (untreated fumed silica) supplied by Cabot, Tuscola, Ill. When incorporated into the film compositions of the present invention, the water insoluble particle is present at a concentration of from about 0.1% to about 20%, optionally from about 0.5% to about 15%, and optionally about 1% at about 10% by weight of the wet film composition. When the film of the present invention forms the first layer or support layer of a multilayer or bilayer film, the thickness of this first layer or support layer may optionally be in the range of about 1 micrometer to about 20 micrometers, optionally about 3 microns to about 15 microns, optionally from about 5 microns to about 12 microns. The thickness of any additional layer may be equal to the thickness range of the first support layer or layer or the range of about 30 micrometers to about 150 micrometers, optionally from about 45 micrometers to about 130 micrometers, optionally from about 70 micrometers to about 120 micrometers Optional ingredients Various topical and systemic active substances can also be incorporated into the films of the present invention. The term "topical or systemic active substance", as used herein, includes curative, prophylactic and cosmetic substances or compositions thereof. Examples of conditions to which these substances may be directed include, but are not limited to, one or more of structural appearance and changes of teeth, whitening, bleaching of spots, stain removal, plaque removal, tartar removal, prevention and treatment. of loss of tooth structure due to caries, inflamed and / or bleeding gums, mucosal wounds, lesions, ulcers, aphthous ulcers, cold sores, dental abscesses, toothaches and / or gums, dental sensitivity (for example, changes in temperature ) and the elimination of the oral malodor resulting from the above conditions and other causes such as microbial proliferation. Additionally, the films of the present invention are useful for treating and / or preventing wounds, lesions, ulcers, cold sores and the like on the lips and on the skin in general. Topical active substances suitable for use in and around the oral cavity include any substance that is generally considered safe for use in the oral cavity and that provides a change in the overall health of the oral cavity. The topical oral hygiene active substance level in the present invention can be generally from about 0.01% to about 40% or, optionally, from about 0.1% to 20% by weight of the wet film. The topical oral hygiene active substances of the present invention may include many of the active substances disclosed in the art. The following is a non-exhaustive list of active oral hygiene substances that can be used in the present invention. The essential oils may be included in or associated with the films of the present invention. Essential oils suitable for use herein are described in detail in U.S. Pat. 6,596,298 to Leung et al., Previously incorporated by reference in its entirety. Teeth whitening active substances can be included in the films of the present invention. The active substances suitable for bleaching are selected from the group consisting of oxalates, peroxides, metal chlorites, perforates, perfluoroes, peroxyacids and mixtures thereof. Suitable peroxide compounds include: hydrogen peroxide, calcium peroxide, sodium peroxide, carbamide peroxide, urea peroxide, sodium percarbonate and mixtures thereof. Optionally, the peroxide is hydrogen peroxide. Suitable metal chlorites include calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, and potassium chlorite. Additional bleaching agents may be hypochlorite and chlorine dioxide. Sodium chlorite is a preferred chlorite. The efficacy of the bleaching active substances can be enhanced, optionally, by means of a catalyst, namely a two-component peroxide catalyst system. Catalysts or catalysts useful as bleaching agents can be found in US Pat. No. 6,440,396 to McLaughlin, Gerald, incorporated herein by reference in its entirety. When peroxide active substances are incorporated, the film compositions of the present invention may optionally contain active peroxide stabilizers. Active peroxide stabilizers suitable for use herein include, but are not limited to, polyethylene glycols such as PEG 40 or PEG 600; zinc salts such as zinc citrate; polyoxyalkylene block polymers (for example Pluronics); aminocarboxylic acids or salts thereof; glycerols; dyes such as blue n ° 1 or green n ° 3; phosphates such as phosphoric acid, sodium phosphate or sodium acid pyrophosphate; stannous salts such as stannous chloride; sodium stannate; citric acid; etidronic acid; carbomers or carboxypolymethylenes such as those of the Carbopol® series, butylated hydroxytoluene (BHT), ethylenediaminetetraacetic acid (EDTA) and mixtures thereof. The anticalculus agents useful herein include phosphates. The phosphates include pyrophosphates, polyphosphates, polyphosphonates and mixtures thereof. Pyrophosphates are among the best known for use in dental hygiene products. The pyrophosphate ions supplied to the teeth are derived from pyrophosphate salts. Pyrophosphate salts useful in the present compositions include dialkaline metal pyrophosphate salts, tetraalkaline metal pyrophosphate salts, and mixtures thereof. Disodium diacid pyrophosphate (Na2H2P2O7), tetrasodium pyrophosphate (Na P2O7) and tetrapotassium pyrophosphate (K P2O7) in their non-hydrated as well as hydrated forms are preferred. The anticalculus phosphates include potassium and sodium pyrophosphates; sodium tripolyphosphate; diphosphonates such as ethane 1-hydroxy-1,1-d-phosphonate; 1-Azacicioheptane 1,1-diphosphonate; and linear alkyl diphosphonates; linear carboxylic acids and sodium and zinc citrate. Agents that can be used in place of or in combination with the pyrophosphate salt include materials such as synthetic anionic polymers, including polyacrylates and copolymers of anhydride or maleic acid and methyl vinyl ether (for example Gantrez, as described for example in US Pat. US 4,627,977 to Gaffar et al., Incorporated herein by reference in its entirety, as well as for example polyaminopropanesulfonic acid (AMPS), zinc citrate trihydrate, polyphosphates (eg tripolyphosphate, hexametaphosphate), diphosphonates (e.g. EHDP, AMP ), polypeptides (1 such as polyaspartic and polyglutamic acids), and mixtures thereof One or more sources of fluoride ion are incorporated into the film compositions as anticaries agents.Fluoride ions are included in many oral hygiene compositions with this Finally, and similarly, they can be incorporated into the invention in the same way. sources of fluoride ion in U.S. Pat. 6,121, 315 of Nair et al., Incorporated herein by reference in its entirety. They are also useful in presenting them with dental desensitizing agents. Dental desensitizing agents that can be used in the present invention include potassium nitrate, citric acid, citric acid salts, strontium chloride and the like, as well as other desensitizing agents known in the art. The amount of desensitizing agent included in the tooth whitening compositions of the present invention may vary according to the concentration of the potassium nitrates, the desired potency and the intended treatment times. Accordingly, if they are included, the other desensitizing agents will preferably be included in an amount in the range of about 0.1% to about 10% by weight of the dental desensitizing composition, more preferably in a range of about 1 to about 7%. by weight of the wet film composition.

Antimicrobial agents may also be present in the film compositions of the present invention in the form of oral agents or topical dermal and / or systemic active substances. Such agents may include, but are not limited to, 5-chloro-2- (2,4-dichlorophenoxy) phenol, usually referred to as triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylamide, domiphene bromide, cetylpyridium chloride (CPC), tetradecylpyridinium chloride (TPC), N-tetradecyl-4-etiipyridinium chloride (TDEPC), octenidin, delmopinol, octapinol and other piperidino derivatives, niacin preparations; zinc / stannous ionic agents, antibiotics such as AUGMENTIN, amoxicillin, tetracycline, doxycycline, minocycline and metronidazole; and analogues, derivatives and salts of the above antimicrobial agents and mixtures thereof. Antiinflammatory agents may also be present in the film compositions of the present invention in the form of oral agents or topical dermal and / or systemic active substances. Such agents may include, but are not limited to, non-steroidal anti-inflammatory agents or NSAIDs, such as propionic acid derivatives, acetic acid derivatives, phenamic acid derivatives, biphenylcarboxylic acid derivatives and oxycarbons. All of these NSAIDs are described in detail in U.S. Pat. No. 4,985,459 of Sunshine et al., issued on January 15, 1991, incorporated as reference to the present in its entirety. Examples of useful NSAIDs include acetylsalicylic acid, ibuprofen, naproxen, benoxaprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, microprofen, thioxaprofen, suprofen, alminoprofen, thiaprofenic acid, fluprofen, bucloxic acid, and mixtures thereof. Also useful are steroidal antiinflammatory drugs such as hydrocortisone and the like, and COX-2 inhibitors such as meloxicam, celecoxib, rofecoxib, valdecoxib, etoricoxib or mixtures thereof. Mixtures of any of the above anti-inflammatories can be used. Anesthetic agents can also be incorporated herein. Examples of suitable anesthetic agents include, but are not limited to, benzocaine, betoxicamine, bifenamine, bupivacaine, butacaine, dibucaine hydrochloride, diclionine, lidocaine, mepivacaine, procaine, propanidide, propanocaine, proparacaine, propipocaine, propofol, propoxycaine hydrochloride, pseudococaine, tetracaine hydrochloride and mixtures thereof. Active substances in the upper respiratory tract can also be used here. Examples of such active substances are sympathomimetic agents administered systemically or topically for decongestant use, including propylhexedrine, phenylephrine, phenylpropanolamine, pseudoephedrine, naphazoline hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, xylometazoline hydrochloride and ethylnorepinephrine hydrochloride; are antihistamines chlorpheniramine, brompheniramine, clemastine, ketotifen, azatadine, loratadine, terfenadine, cetirizine, astemizole, taziphiline, levocabastine, diphenhydramine, temelastin, etolotifen, acrivastine, azelastine, ebastine, mequitazine, mizolastin, levocetirizine, mometasone furoate, carebastine, ramatroban, desloratadine, noberastine, selenotifen, alinastine, efletirizin, tritocualin, norastemizole, tagorizin, epinastine, acrivastin and mixtures thereof; antitussives such as dextromethorphan, benzonatate and guifenecine and mixtures thereof. Other active substances in the upper respiratory tract useful in U.S. Pat. 4,619,934, incorporated herein by reference in its entirety. Gastrointestinal active substances can also be incorporated. Examples of suitable gastrointestinal active substances include anticholinergics, including: atropine, clidinium and dicyclomin; antacids, including aluminum hydroxide, basic bismuth salts such as bismuth subsalicylate, ranitidine bismuth citrate, bismuth subcitrate, bismuth subnitrate, aluminum or bismuth salts of polysulphated saccharides such as sucrose octasulfate of aluminum or sucrose octasulfate of bismuth, simethicone, calcium carbonate and magaldrate (other examples of antacids can be found in 21 CFR 331.11, which is incorporated herein by reference); H (2) receptor antagonists, including cimetidine, famotidine, nizatidine and ranitidine; laxatives, including: bisacodyl, picosulfate and casantrol (other examples of laxatives can be found in the Federal Register, vol 50, no 10, January 15, 1985, page 2152-2158, which is incorporated herein by reference); Gastroprotectors, including sucralfate and wet sucralfate gel; gastrokinetic and prokinetic agents, including cisapride, metoclopramide and eisaprode; proton pump inhibitors, including omeprazole, lanzoprazole and antidiarrheals, including: diphenoxylate and loperamide; agents that are bacteriostatic and bactericidal for the ulcer-inducing organism Heliobacter pylori, such as amoxicillin, metronidazole, erythromycin or nitrofurantoin and other agents for treating H. pylori disclosed in U.S. Pat. No. 5,256,684, which is incorporated herein by reference in its entirety; polyanionic materials useful for the treatment of ulcers and other gastrointestinal disorders, including amylopectin, carrageenan, sulfated dextrins, inositol hexaphosphate or other similar agents and mixtures thereof. The nutrients can improve the condition of the oral cavity and can be included in the oral hygiene substances or compositions of the present invention. Examples of nutrients include minerals, vitamins, oral nutritional supplements, enteral nutritional supplements and mixtures thereof. Smoking cessation agents such as nicotine can also be incorporated into the film compositions of the present invention. A single enzyme or combination of several compatible enzymes may also be included in the oral hygiene substance or composition of the present invention. Enzymes are biological catalysts of chemical reactions in living beings. The enzymes are combined with the substrates on which they act forming an enzyme-substrate intermediate complex. This complex is then converted into a reaction product and a released enzyme, which continues its specific enzymatic function. Enzymes provide several benefits when used for cleaning the oral cavity. Proteases degrade salivary proteins, which are absorbed on the surface of the teeth and form the film; the first layer of the resulting plate. The proteases together with the lipases destroy the bacteria using proteins and lipids that form the structural component of the walls and membranes of the bacterial cell. Dextranases degrade the organic skeletal structure produced by bacteria that forms a matrix for bacterial adhesion. Proteases and amylases that are not only present in plaque formation, but also prevent the development of stones by degrading the protein complex of carbohydrate that binds to calcium, preventing mineralization. Enzymes useful in the present invention include any of the commercially available proteases, glucanhydrolases, endoglycosidases, amylases, mutanases, lipases and mucinases or compatible mixtures thereof. Preferred are proteases, dextranases, endoglycosidases and mutenases, with papain, endoglycidase, lysozyme or a mixture of dextranase and mutanase being more preferred. Other materials that can be used with the present invention include commonly known mouth and throat products. These products include, but are not limited to, antifungal agents, antibiotics and analgesics. Antioxidants are generally recognized to be useful in compositions such as those of the present invention. Antioxidants that may be included in the composition or oral hygiene substance of the present invention include, but without limitation, vitamin E, ascorbic acid, uric acid, carotenoids, vitamin A, flavonoids and polyphenols, herbal antioxidants, melatonin, aminoindoles, lipoic acids and mixtures thereof. Histamine receptor antagonist compounds (H-2) (H-2 antagonists) can be used in the oral hygiene composition of the present invention. As used herein, selective H-2 antagonists are compounds that block H-2 receptors, but have no significant activity in blocking histamine (H-1) receptors. Additional useful active substances can be found in U.S. Pat. 6,638,528, incorporated herein by reference in its entirety. An additional carrier material may also be added to the film composition of the present invention. These materials may be added as additional components for properties other than those indicated above, and may include humectants and include glycerin, sorbitol, polyethylene glycol, and the like. The film composition may comprise the substance itself, together with one or more enhancers of the substance, for example catalysts and / or enhancers to modify the release and / or activity of the substance. The film compositions of the invention may additionally comprise additional substances such as flavors, colorants, etc., which may be deposited for example on the surface of the film or impregnated in the volume of the film. The topical or systemic active substance is preferably a tooth whitening substance. The tooth whitening substance can take the form of a peroxide-containing gel. Suitable gels can be based on glycerol containing a peroxide such as hydrogen peroxide or an organic peroxide. It is a suitable gel that is disclosed in document US-A-3,657,413, for example that marketed under the trade name PROXIGEL by The Block Drug Company (USA) (acquired by GlaxoSmithKline foot). Other suitable peroxide-containing gels are, for example, those disclosed in the prior art references. The film may have the topical or systemic active substance deposited on its surface. A pH adjusting agent may also be added to optimize the storage stability of the gel and to make the substance safe for oral tissues. These pH adjusting agents, or regulators, can be any material that is suitable for adjusting the pH of the oral hygiene substance. Suitable materials include sodium bicarbonate, sodium phosphate, sodium hydroxide, ammonium hydroxide, sodium stannate, triethanolamine, citric acid, hydrochloric acid, sodium citrate and combinations thereof. The pH adjusting agents are added in amounts sufficient to adjust the pH of the substance or composition to a suitable value, for example from about 4.5 to about 11, preferably from about 5.5 to about 8.5, and more preferably from about 6 to about 7. The pH adjusting agents are generally present in an amount from about 0.01% to about 15%, and preferably from about 0.05% to about 5% by weight of the oral hygiene substance. For example, a gel can be deposited directly in the form of a layer on a surface of a film layer as described above. Alternatively, a gel can be absorbed in the film layer described above, or impregnated in the volume of the film material, or deposited between the layers of a multilayer film. The methods of deposition of the substances on the surfaces of film materials as described above are known, for example printing, for example screen printing, passing between impregnated rolls, dosing, pump and nozzle, spraying, dipping, etc. Methods of impregnation of substances in the volume of the film material are also known, for example mixing of the substance with the strip material and formation after the strip, or exposure of the strip to the substance under conditions which cause the substance to soak in the strip. Alternatively, an example of a film material may be a foamed material, particularly an open-celled foamed material, and the substance may be impregnated in the strip material by introducing the substance into the foam cells.

In another embodiment, the film of the present invention forms the first layer or support layer of a bilayer, wherein the second layer is a layer of water soluble polymeric film such as that described in U.S. Pat. 6,596,298 from Leung eí to /. and 6,419,903 to Xu et al., both incorporated herein by reference in their entirety. The bilayer film is then applied to the teeth, oral mucosa or other affected area of the skin or mouth and allowed to disintegrate over time in the presence of saliva or other aqueous medium. Additionally, the film layers of the present invention can be made using heat melt extrusion techniques such as those described in U.S. Pat. 6,375,963 B1 of Repka et al., Incorporated herein by reference in its entirety. The device of the invention can be marked with one or more visible symbols, for example written material, a trademark, a company logo, a colored area or an alignment feature such as a visible line or notch, etc., to assist the user to apply the device to the teeth with proper alignment. Said alignment feature may for example comprise a symbol to show the user what the upper side of the device should be while the device is applied to the teeth, or which of a pair of devices is intended for the upper teeth and which for the lower teeth . In this way the device can be made visually more attractive and / or easier to use. Said symbol (s) can be applied by conventional printing or stamping processes, for example screen printing, ink jet printing, etc. on the surface of the plastically deformable material opposite the surface on which the layer of an absorbent material is attached. If said visible symbol is applied to this surface, a cover layer may optionally be applied over the symbol, for example to protect it. This cover layer can be transparent or translucent to allow visible symbols to be seen through this layer. Said cover layer can optionally be applied to the film by pressing, for example with rollers, the material of the cover layer in contact with the film.

Methods for delivering topical and systemic active substances The present invention can be used where retention of the topical or systemic active substance is necessary for topical activity or adequate systemic absorption. The film compositions of the present invention are particularly useful for whitening tooth surfaces. Generally, the delivery of the teeth whitening active substances involves the topical application of the invention film containing a safe and effective amount of said active compounds to a tooth or teeth and gums in the manner described in US Pat. UU 5,894,017, 5,891, 453, 6,045,811 and 6,419,906, each of which is incorporated herein by reference in its entirety. The frequency of application and the period of use will vary widely depending on the level of treatment required or desired, for example the degree of tooth whitening and / or the degree of healing / disinfection of topical wound desired. When applied in the form of a skin or mucosa patch, the films of the present invention may be useful for problematic areas of the skin that need more intensive treatment or for the transdermal delivery of drugs. The patch may be occlusive, semi-occlusive or non-occlusive. The topical or systemic active substances of the present invention may be contained in or coated on the surface of the film or applied to the skin prior to the application of the film. Additionally, the film can be applied wet to form a film when it is dried over the application area. The film may also include active substances such as chemical initiators for exothermic reactions such as those described in PCT application WO 9701313 to Burkett et al. Optionally, the film can be applied overnight in the form of night therapy. Examples of transdermal systems useful in U.S. Pat. 3,598,122, 3,598,123, 3,731, 683, 3,797,494, 4,286,592, 4,314,557, 4,379,454, 4,435,180, 4,559,222, 4,568,343, 4,573,999, 4,588,580, 4,745,502, 4,704,282, 4,816,258, 4,849,226, 4,908,027, 4,943,435 and 5,004,610, all of which are incorporated herein by reference In its whole. Active substances commonly associated with transdermal delivery are disclosed in U.S. Pat. 5,843,468 and 5,853,751, both incorporated herein by reference in their entirety.

EXAMPLES The film compositions illustrated in the following examples illustrate specific embodiments of the film compositions of the present invention, but are not intended to be limiting thereof. Other modifications may be undertaken by one skilled in the art without departing from the essence and scope of this invention. All exemplified film compositions can be prepared by conventional formulation and mixing techniques. The component quantities are listed as percentages by weight and exclude minority materials such as diluents, fillers and so forth. The formulations listed, therefore, comprise the listed components and any minor material associated with said components.

EXAMPLE I The following is an example of an independent film of the present invention. 1 Supplied under the trade name Cabosil® by Cabot, Tuscola, 2 Corn protein (supplied by Freeman Industries, Tuc ahoe, NY).

In a suitable beaker are mixed ceine, silica, alcohol, glycerin and water until uniformity and homogeneity. Then, the contents of the beaker are poured to the desired thickness on a non-tacky surface or sheet at room temperature to form the invention.

EXAMPLE II The following is an example of an independent film of the present invention. 2 Contains ethanol, shellac, hydrogenated vegetable oil (coconut origin) (supplied by Centerchem, Inc., Norwalk, CT).

Capol 150, silica and alcohol are mixed in a suitable beaker until uniformity and homogeneity. Then, the contents of the beaker are poured to the desired thickness on a non-tacky surface or sheet at room temperature to form the invention.

EXAMPLE III The following is an example of a paint film forming composition of the present invention.

INGREDIENT QUANTITY (percentage by weight) PHARMACEUT1CAL GLAZE '56.00 MAGNESIUM STEARATE 3.00 TRIACETINUM 1, 00 ALCOHOL USP / EP 40.00 1 Lacquer gum supplied by Mantrose Haeser Co., Attleboro, Ma. 2 Magnesium stearate, Hyqual , vegetable source supplied by Mallinckrodt Chemicals, Phillipsburg, NJ. 3 Eastman Triacetin (food purity) supplied by Eastman Chemical Company, Kingsport, TN.

In a suitable beaker, Pharmaceutical Glaze, magnesium stearate, triacetin and alcohol are mixed until uniform and homogeneous. The contents of the beaker are then placed in an airtight container suitable for subsequent application to the skin, teeth or oral mucosa by the consumer in the form of a paint film.

EXAMPLE IV The following is an example of a bi-layered teeth whitening film of the present invention. Ca to adhesive Support layer PHARMACEUTICAL GLAZE, 4-LB CUT 55.0000% p / p NF 10 SILICA11 (untreated smoker) 4.0000% p / p ALCOHOL USP / EP 40.0000% p / p GLYCERYL ESTEARATE SE 1.0000% p / p Supplied with the name Keltrol T by CP Kelco, Chicago, IL 2 Marketed under the name Viscogum BCR 20/80 by Degussa Texturant Systems, Atlanta, GA 3 Supplied with the name Viscarin SD339 by FMC Biopolymer, Philadelphia, PA 4 Purity PI-20 , supplied by Hayashibara, 5 Poly (vinylpyrrolidone), USP K-90, International Specialties Products (ISP), Wayne, NJ. 6 Hydrogen peroxide solution ALB CG 35%, Atofina, Philadelphia, PA. 7 Supplied under the trade name Spienda® by McNeil Pharmaceuticals, New Brunswick, NJ. 8 Tween 80, supplied by Quest, Hoffmann Estates, lll. 9 Mixture of mono- and dioleatos supplied with the name Atmos 300 by American Ingredients, Kansas City, Mo. 10 Shellac Gum supplied by Mantrose Haeser Co., Attleboro, Ma. 11 Supplied under the tradename Cabosil® by Cabot, Tuscola, lll . 12 Supplied in the form of mono- and diglycerides of fats and oils (available purity) by Lonza Inc., Fairlawn, NJ.

They are added in a suitable beaker (beaker A), water, sucralose and potassium phosphate monobasic with mixing until the mixture is homogeneous. Mix in a separate beaker (beaker B), xanthan gum, locust bean gum, carrageenan, pullulan and Plasdone K-90 as a dry mix until the mixture is homogeneous. The contents of vessel B are mixed in vessel A with mixing or rapid stirring. The combined mixture is mixed until the gums are hydrated. The hydrogen peroxide is slowly added to the combined mixture with stirring. In a separate vessel (cup C), the aroma is mixed, polysorbate 80, glycerin and Atmos 300 until dissolution and uniformity. The contents of vessel C are then poured into vessel A and mixed until the mixture is uniform and homogeneous. The pH is then adjusted to approximately 5.5 using 1.0 N sodium hydroxide. In yet another separate vessel (vessel D), Pharmaceutical Glaze, Cabosil, alcohol and glyceryl stearate are mixed until uniform and homogeneous. The contents of the glass D are then poured to the desired thickness on a non-tacky surface at room temperature to form the film or the first layer of the bilayer tooth whitening film of the invention. The contents of vessel A are then poured to the desired thickness on the first layer described above at room temperature to form the second layer of the bilayer film of teeth whitening.

EXAMPLE V The following is an example of a bilayer film of teeth whitening of the present invention. Ca to adhesive Marketed under the name Viscogum BCR 20/80 by Degussa Texturant Systems, Atlanta, GA. 3 Supplied with the name Viscarin SD339 by FMC Biopolymer, Philadelphia, PA. 4 Poly (vinylpyrrolidone), USP K-90, International Specialties Products (ISP), Wayne, NJ.

Hydrogen peroxide solution ALB CG 35%, Atofina, Philadelphia, PA. 6 Supplied under the tradename Spenda® by McNe / l Pharmaceuticals, Philadelphia, Pa. 7 Tween 80, supplied by Quest, Hoffmann Estates, Ill. 8 Mixture of mono- and dioleatos supplied with the name Atmos 300 by American Ingredients, Kansas City, Mo. 9 Shellac Gum supplied by Mantrose Haeser Co., Attleboro, Ma. 10 Supplied under the tradename Cabosil® by Cabot, Tuscola, lll . 11 Supplied in the form of mono- and diglycerides of fats and oils (available purity) by Lonza Inc., Fairlawn, NJ.

They are added in a suitable beaker (vessel A), water, sucralose and potassium phosphate monobasic with mixing until the mixture is homogeneous. In a separate beaker (beaker B), xanthan gum, locust bean gum, carrageenan and Plasdone K-90 are mixed as a dry mixture until the mixture is homogeneous. The contents of vessel B in vessel A are mixed with rapid mixing or stirring. The combined mixture is mixed until the gums are hydrated. The hydrogen peroxide is added slowly to the mixed mixture with mixing. In a separate vessel (cup C), the aroma is mixed, polysorbate 80, glycerin and Atmos 300 until dissolution and uniformity. The contents of vessel C are then poured into vessel A and mixed until the mixture is uniform and homogeneous. The pH is then adjusted to approximately 5.5 using 0.1 N sodium hydroxide. In yet another separate vessel (vessel D), Pharmaceutical Glaze, Cabosil, alcohol and glyceryl stearate are mixed until uniform and homogeneous. The contents of the glass D are then poured to the desired thickness on a non-tacky surface at room temperature to form the film or the first layer of the bilayer film of teeth whitening of the invention. The contents of vessel A are then poured to the desired thickness over the first layer described above at room temperature to form the second layer of the bilayer film of teeth whitening.

EXAMPLE VI The following is an example of a bilayer film of teeth whitening of the present invention. Ca to adhesive Support layer PHARMACEUTICAL GLAZE, 4-LB CUT NFS 55.0000% p / p SILICA "(untreated smoker) 4.0000% p / p ALCOHOL USP / EP 40.0000% p / p GLYCERY ESTEARATE SE" 1.0000% p / p 1 Supplied with the name Keltrol T by CP Kelco, Chicago, 1L. 2 Marketed under the name Viscogum BCR 20/80 by Degussa Texturant Systems, Atlanta, GA. 3 Purity Pl-20, supplied by Hayashibara. Poly (vinylpyrrolidone), USP K-90, International Specialties Products (ISP), Wayne, NJ.

Hydrogen peroxide solution ALB CG 35%, Atofina, Philadelphia, PA. 6 Supplied under the trade name Spenda® by McNeil Pharmaceuticals, Philadelphia, Pa. 7 Tween 80, supplied by Ouest, Hoffmann Estates, ill. 8 Mixture of mono- and dioleatos supplied with the name Atmos 300 by American Ingredients, Kansas City, Mo. 9 Shellac Gum supplied by Mantrose Haeser Co., Attleboro, Ma. 0 Supplied under the tradename Cabosil® by Cabot, Tuscola, lll . 1 Supplied in the form of mono- and diglycerides of fats and oils (available purity) by Lonza Inc., Fairlawn, NJ.

They are added in a suitable beaker (vessel A), water, sucralose and potassium phosphate monobasic with mixing until the mixture is homogeneous.

In a separate beaker (beaker B), xanthan gum, locust bean gum, pullulan and Plasdone K-90 are mixed as a dry mixture until the mixture is homogeneous. The contents of vessel B in vessel A are mixed with rapid agitation or mixing. The combined mixture is mixed until the gums are hydrated. Hydrogen peroxide is added slowly to the combined mixture with mixing. In a separate vessel (cup C), the aroma is mixed, polysorbate 80, glycerin and Atmos 300 until dissolution and uniformity. The contents of vessel C are then poured into vessel A and mixed until the mixture is uniform and homogeneous. The pH is then adjusted to approximately 5.5 using 1.0 N sodium hydroxide. In yet another separate vessel (vessel D), Pharmaceutical Glaze, Cabosil, alcohol and glyceryl stearate are mixed until uniform and homogeneous. The contents of the glass D are then poured to the desired thickness on a non-tacky surface at room temperature to form the film or the first layer of the bilayer tooth whitening film of the invention. The contents of vessel A are then poured to the desired thickness over the first layer described above at room temperature to form the second layer of the bilayer film of teeth whitening.

EXAMPLE VII The following is an example of a bilayer tooth whitening film of the present invention. Ca to adhesive Corporation, Muscatine, IA. 2 Supplied with the name Bright Gum Arabic Dry Spray FCC / INF Powder by TIC Gums, Belcamp, MD. 3 Purity PI-20, supplied by Hayashibara. 4 Poly (vinylpyrrolidone), USP K-90, International Specialties Products (ISP), Wayne, NJ. 5 Hydrogen peroxide solution ALB CG 35%, Atofina, Philadelphia, PA. 6 Supplied under the trade name Spenda® by McNeil Pharmaceuticals, Philadelphia, Pa. 7 Tween 80, supplied by Ouest, Hoffmann Estates, Ill. 8 Mixture of mono- and dioleatos supplied with the name Atmos 300 by American Ingredients, Kansas City, Mo. 9 Shellac Gum supplied by Mantrose Haeser Co., Attleboro, Ma. 10 Supplied under the tradename Cabosil® by Cabot, Tuscola, Supplied in the form of mono- and diglycerides of fats and oils (available purity) by Lonza Inc., Fairlawn, NJ.

They are added in a suitable beaker (vessel A), water, sucralose and potassium phosphate monobasic with mixing until the mixture is homogeneous.

In a separate beaker (beaker B), starch gum, gum arabic, pullulan and Plasdone K-90 are mixed as a dry mixture until the mixture is homogeneous. The contents of vessel B in vessel A are mixed with rapid agitation or mixing. The combined mixture is mixed until the gums are hydrated. Hydrogen peroxide is added slowly to the combined mixture with mixing. In a separate vessel (cup C), the aroma is mixed, polysorbate 80, glycerin and Atmos 300 until dissolution and uniformity. The contents of vessel C are then poured into vessel A and mixed until the mixture is uniform and homogeneous. The pH is then adjusted to approximately 5.5 using 1.0 N sodium hydroxide. In yet another separate vessel (vessel D), Pharmaceutical laze, Cabosil, alcohol and glyceryl stearate are mixed until uniform and homogeneous. The contents of the glass D are then poured to the desired thickness on a non-tacky surface at room temperature to form the film or the first layer of the bilayer tooth whitening film of the invention. The contents of vessel A are then poured to the desired thickness over the first layer described above at room temperature to form the second layer of the bilayer film of teeth whitening.

Claims (15)

NOVELTY OF THE INVENTION CLAIMS

1. - A film composition comprising: a) at least one water-insoluble polymer; b) at least one disintegration enhancer selected from the group consisting of water-insoluble particulates, plasticizer and mixtures thereof, c) optionally, at least one topical or systemic active substance in which the film is disintegrable in an aqueous environment .

2. The film composition according to claim 1, further characterized in that the water-insoluble polymer is selected from the group consisting of hydrogenated vegetable oils, hydrogenated castor oil, polyvinyl chloride, shellac, polyurethane, cellulose derivatives, rubber rosins, wood rosins, waxes, acrylate and methacrylate polymers, copolymers of acrylic and methacrylic acid esters or mixtures thereof.

3. The film composition according to claim 2, further characterized in that the water-insoluble polymer is shellac.

4. The film composition according to claim 1, further characterized in that the plasticizer is selected from the group consisting of alkyl esters of citric acid, esters of glycerol, alkyl esters of phthalic acid, alkyl esters of sebacic acid, esters of sucrose , sorbitan esters, acetylated monoglycerides, glycerols, glycols, fatty acid esters, propylene glycol, poloxamers, alkylaryl phosphates and polyethylene glycols 200 to 12,000 and their mixtures.

5. The film composition according to claim 4, further characterized in that the plasticizer is glycerol monostearate.

6. The film composition according to claim 1, further characterized in that the particulate material insoluble in water is selected from the group consisting of alumina, talc, titanium dioxide, magnesium stearate, barium titanate, magnesium titanate, titanate Calcium, strontium titanate, zinc oxide, silica sand, clay, mica, wollastonite, diatomaceous earth, various inorganic oxide pigments, chromium oxide, cerium oxide, iron red, antimony trioxide, magnesium oxide, zirconium oxide, barium sulfate, barium carbonate, calcium carbonate, silica, silicon carbide, silicon nitride, boron carbide, tungsten carbide, titanium carbide, carbon black and mixtures thereof.

7. The film composition according to claim 6, further characterized in that the water-insoluble polymer is fuming silica.

8. The film composition according to claim 1, further characterized in that it additionally comprises at least one topical or systemic active substance.

9. The film composition according to claim 1, further characterized in that the topical or systemic active substance is selected from the group consisting of bleaching agents, anticalculus agents, fluoride ion sources, antimicrobial agents, anti-inflammatory agents, respiratory tract agents superior, gastrointestinal agents, enzymes, antifungals, antibiotics, analgesics, histamine antagonists and mixtures thereof.

10. A multilayer film composition comprising at least two layers of film, wherein at least one layer comprises: a) at least one water-insoluble polymer; b) at least one disintegration enhancer selected from the group consisting of water-soluble particulates, plasticizers and mixtures thereof; and c) optionally, at least one topical or systemic active substance; where the film is disintegrable in an aqueous environment.

11. The film composition according to claim 10, further characterized in that it additionally comprises at least one topical or systemic active substance.

12. The film composition according to claim 11, further characterized in that the topical or systemic active substance is selected from the group consisting of bleaching agents, antisera agents, fluoride ion sources, antimicrobial agents, anti-inflammatory agents, upper respiratory tract agents, gastrointestinal agents, enzymes, antifungals, antibiotics, analgesics, histamine antagonists and mixtures thereof.

13. The film composition according to claim 12, further characterized in that the topical or systemic active substance is a bleaching agent.

14. The film composition according to claim 13, further characterized in that the bleaching agent is selected from the group consisting of peroxides, metal chlorites, perforates, percarbonates, peroxyacids and mixtures thereof.

15. The film composition according to claim 14, further characterized in that the bleaching agent is hydrogen peroxide.