MXPA01001539A - Fast dissolving orally consumable films - Google Patents

Abstract

Physiologically acceptable films, including edible films, are disclosed. The films include a water soluble film-forming polymer such as pullulan. Edible films are disclosed that include pullulan and antimicrobially effective amounts of the essential oils thymol, methyl salicylate, eucalyptol and menthol. The edible films are effective at killing the plaque-producing germs that cause dental plaque, gingivitis and bad breath. The film can also contain pharmaceutically acitve agents. Methods for producing the films are also disclosed.

Description

QUICK DISSOLUTION FILMS ORALALLY CONSUMABLES FIELD OF THE INVENTION This invention relates to fast dissolving films consumable orally. The films are used to release breath deodorizing agents, microbial agents and salivary stimulants from the oral cavity. Said films can also be used to release pharmaceutically active agents. BACKGROUND OF THE INVENTION In a perfect world, people would carefully wash their mouths after each meal, as part of their routine oral hygiene practices. Unfortunately, several factors concur to prevent compliance with this basic requirement of a good oral cleansing regimen.

Sometimes oral cleansing can be difficult or inconvenient, depending on its nature and the situation in which it should occur. Brushing, flossing, tongue cleaning and mouthwash using a wide variety of devices and compositions perfectly suited for home privacy are common oral care practices. However, the devices and compositions used in oral cleansing practices are not very convenient to use outside the home, where the facilities of a bathroom can be few, not available or unsanitary.

Like brushing, flossing, cleaning the tongue and using mouthwash, in public; they are not socially accepted behaviors in many, but in all cultures, a wide variety of oral cleaning products has been developed less annoying. These products include chewing gums, breath fresheners and pills. Although chewing gums and pills have been formulated to achieve various beneficial effects, they are not always socially acceptable. For example, chewing gum is expressly prohibited in certain institutions such as schools, as well as in certain countries, such as Singapore. Chewing gums and mints are used for a long time and require a large amount of chewing or suction from the consumer, which can be unsettling, tedious and undesirable.

Another portable oral cleansing product is a mouth spray. Similar to a mouthwash, an oral spray can provide the consumer with a quick and strong cooling sensation of breath, which can be crippling in a prolonged consumer product similar to chewing gum or pills. On the other hand, oral sprays are annoying. In general, the spray of a mouth spray generates a noise that undesirably diverts the attention of the public to the consumer. In addition, mouth sprays are typically packaged in relatively expensive and complex metal cans, which can hinder their use and are not compatible with the environment. In addition, the incorrect direction of the spray not only wastes the product, but can result in irritated eyes, sticky face and / or stained clothing.

It has been proposed to use an edible film as a vehicle to release, without obstruction, breath freshening agents. See document JP 5-236885. However, said Japanese patent application does not disclose the inclusion of antimicrobial agents in the film, using the same to decrease the amount of undesirable bacteria within the oral cavity, or to stimulate saliva. Furthermore, this patent application also does not describe the use of its film for other purposes than freshening the breath, or in other cavities than the mouth.

The Patent of E.U.A. No. 5,518,902 to Ozaki et al (Hayashibara) describes products with high pullulan content, such as edible films, dentifrices and pharmaceuticals (column 3, lines 44-56 and Example B-8). The products may include a wide variety of ingredients in addition to pullulan, such as other polysaccharides, polyhydric alcohols, antiseptics and flavoring agents (column 4, line 58 to column 5, line 11). None of the essential oils such as thymol, eucalyptol, methyl salicylate or menthol are mentioned as suitable ingredients.

The Patent of E.U.A. No. 5,411, 945 of Ozaki et al (Hayashibara) discloses a pullulan binder and the products made therefrom, including edible films (Example B-2). The products may include a wide variety of ingredients in addition to pullulan, such as other polysaccharides, antibacterial agents, flavoring agents and pharmaceutically active substances (column 4, lines 5-15). None of the essential oils is mentioned as an appropriate ingredient.

The Patent of E.U.A. No. 4,851, 394 of Kubodera discloses edible glucomannan / polyhydric alcohol films, which may comprise pullulan (column 3, line 59 to column 4, line 21). These films contrast with the existing films based on pullulan, which lack water resistance (column 1, lines 40-44). None of the essential oils is mentioned as an appropriate ingredient.

The Patent of E.U.A. No. 3,784,390 to Hijiya et al describes pullulan films and their use for coating and packaging materials for food and pharmaceutical products and other oxygen-sensitive materials. All the examples of this patent indicate to mix the pullulan with hot water.

The Patent of E.U.A. No. 4,623,394 to Nakamura et al discloses a molded article capable of gradually disintegrating, which may be a film made of pullulan. The articles contain a particular heteromanan, which can be locust bean gum.

The Patent of E.U.A. No. 4,562,020 to Hijiya et al discloses a process for producing a self-supporting film of a glucan, which can be pullulan.

Japanese Patent Document JP5-1198 discloses films made of polyvinyl alcohol and at least one of carrageenan, water-soluble alpha-cellulose starch and water-soluble polysaccharides.

The application WO 99/17753 describes rapid dissolution films for the release of the drugs to be adsorbed in the digestive tract.

The application WO 98/26780 describes a flat type, thin metal sheet, paper or wafer presentation for the application and release of active substances in the oral cavity. The specific active ingredient described in the application WO 98/26780 is buprenorphine.

The application WO 98/20862 describes a film for use in the oral cavity, which may contain a cosmetic or an active pharmaceutical substance.

The application WO 98/26763 describes a similar presentation of flat type, thin metal sheet, paper or wafer, to release active substances in the oral cavity. The particular asset described is apomorphine.

Despite the existence of fast dissolving films orally consumed by the prior art, there is still a need to improve them and also improve the processes for their manufacture.

All references cited in this document are incorporated in their entirety. SUMMARY OF THE INVENTION The invention provides a physiologically acceptable film, which is particular and perfectly adaptable to adhering to and dissolving rapidly in the mouth of a consumer. In a first embodiment of the invention, the invention releases at least one oral care agent, which may be, for example, an antimicrobial agent and / or a salivary stimulant. Antimicrobial agents are effective against the germs that cause halitosis, microbial dental plaque and gingivitis. Salivary stimulants are effective against the condition known as xerostomia or dry mouth. In addition, oral care films are breath fresheners, effective against odor. The first film used to manufacture the films according to the present invention traps oral care agents within the oral cavity to provide greater efficacy.

In a second embodiment of the invention, the rapidly dissolvable film acts as a vehicle for orally administering a pharmaceutically active agent, through a mucous membrane or an open wound of a patient.

The invention is also directed to a method for producing a flexible, non-self-adhering film, especially suitable for oral delivery. The method comprises mixing a film-forming agent and at least one stabilizing agent to provide a film-forming mixture, dissolving the water-soluble ingredients to provide an aqueous solution, combining the film-forming mixture and the aqueous solution to provide an aqueous solution. hydrated polymer gel, mixing the oils to form an oily mixture, adding the oily mixture to the hydrated polymeric gel and mixing everything to provide a uniform emulsified gel, emptying the uniform gel onto a substrate and drying the drained gel to obtain a film.

BRIEF DESCRIPTION OF THE DRAWINGS 10 Fig. 1 is a photograph of an agar plate extension with Streptococcus mutans, ATCC 25175, exposed to a film according to the present invention containing 0.391 mg of essential oils.

Fig. 2 is a photograph of an agar plate extension with Streptococcus mutans, ATCC 25175, exposed to drops of a mixture of essential oils containing 0.391 mg of essential oils per drop.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES 20 Description of the Compositions of the Oral Care Film The first embodiment of the invention is a physiologically acceptable film that is particular and perfectly adaptable to adhere to and dissolve in the mouth of a consumer to release an antimicrobial agent that kills germs that cause halitosis, dental microbial plaque and gingivitis. Therefore, the film can be an effective tool in the prevention and treatment of halitosis, the accumulation of dental microbial plaque, the accumulation of dental plaque and gingivitis. This film preferably comprises pullulan, thymol, methyl salicylate, eucalyptol and menthol.

LISTERINE® mouthwash is, perhaps, the best-known example of an oral antiseptic composition that has proven effective in killing the microbes responsible for dentobacterial plaque, gingivitis and bad breath in the oral cavity. LISTERINE® mouth rinse achieves its antimicrobial effect through a combination of essential oils that penetrate and kill microorganisms. Such essential oils include exactly balanced amounts of thymol, methyl sallcylate, menthol and eucalyptol (hereinafter referred to as "essential oils") in a hydroalcoholic solution. Many bacteria that cause bad breath live in depressions or fissures on the surface of the tongue. The LISTERINE® antiseptic rinse reduces bad breath because high concentrations of antimicrobial agents in a liquid medium can easily penetrate such depressions or fissures. This would not be possible with a solid dosage form containing low amounts of said antimicrobial ingredients. However, the preferred edible film of the invention captures a significant portion of the hygienic benefits and the consumer resorts to LISTERINE® mouthwash in a more portable form and not consumed in an annoying manner.

It was a significant challenge to maintain the interaction of the essential oil and the relatively high oil content of the LISTERINE® rinse in a film. However, it has been overcome by providing the film of the invention.

A further aspect of this invention is that while the quantities of LISTERINE® essential oils are relatively high to be incorporated into a film, the film according to the present invention still releases a lower total amount of essential oils per unit dose , compared to that released by the LISTERINE® mouthwash. Surprisingly, the film provides antimicrobial efficacy in the oral cavity. It is thought that the preferred film-forming ingredient, pullulan, forms a thin layer on the oral surfaces, trapping the small amount of essential oils that is able to penetrate the depressions and fissures of the oral cavity to provide sustained antimicrobial efficacy .

JP 5-236885 describes a film having a breath freshening activity, but does not disclose that it possesses any of the ingredients that have a significant antimicrobial activity. Additionally, it discloses that said film may contain flavor and extract in amounts of 5 to 7% by weight, the flavor being added as an oil (essential oils are not described), while the film of the invention preferably has an oil content. of at least about 10% by weight, more preferably about 15% by weight to about 30% by weight, more preferably about 15% by weight to about 25% by weight. Except where otherwise indicated in the examples, the amounts of oils and other ingredients of the film are percentages by weight, after the formulation thereof has been dried to create it.

The amounts used of the specific essential oils in the film compositions may vary, as long as they are in sufficient amounts to provide antimicrobial efficacy. Generally, the amount of thymol, methyl salicylate and eucalyptol is from about 0.01 to about 4% by weight of the film composition, preferably about 0.50 to about 3.0% by weight and even more preferably from about 0.70 to about 2.0% by weight. weight of the movie. Menthol can be added from about 0.01 to about 15% by weight of the composition, preferably about 2.0 to about 10% by weight and even more preferably from about 3 to about 9% by weight of the film. The added amounts can be readily determined by those skilled in the art and can exceed the above amounts until the total oil content does not cause adhesion or other processing problems. In certain modalities, essential oils combine in synergistically effective amounts to kill the germs that cause dentobacterial plaque, gingivitis and bad breath.

A major difficulty in formulating a film having such relatively high oil content is that by simply increasing the amount of oil in the film without determining the precise proportions of the other many ingredients; typically results in a film that is too wet and therefore difficult to handle or process. The invention provides a film with a high oil content that is sufficiently moist, so that it is not brittle, but is not so wet as to feel undesirably viscous or significantly adhere to adjacent films. In this way, a non-self-adhering film according to the invention can be stored in contact with another (for example, in a stack of films), or it can be wrapped around itself (for example, around a reel) , without a non-adhesive agent (eg, a plastic film, paper or other support) between the adjacent portions of the film.

The film-forming agent used in the films according to the present invention may be selected from the group consisting of pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan, gum tragacanth, guar gum, acacia gum, gum arabic, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, high hydroxypropylated amylose starch, dextrin, pectin, quitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, isolated protein from soy, protein isolated from whey, casein and mixtures thereof. A preferred film former is pullulan, in amounts ranging from about 0.01 to about 99% by weight, preferably about 30 to about 80% by weight, more preferably from about 45 to about 70% by weight of the film and even more preferably, from about 60 to about 65% by weight of the film.

The film of the invention preferably comprises pullulan as a film-forming agent and essential oils as antimicrobial / flavoring agents and may further comprise water, additional antimicrobial agents, additional film-forming agents, plasticizing agents, additional flavoring agents, precipitating agents sulfur, saliva stimulating agents, cooling agents, surfactants, stabilizing agents, emulsifying agents, thickening agents, binding agents, coloring agents, sweeteners, fragrances and the like.

Due to the relatively high content of oil in the oral care film, it is preferable to avoid large amounts of humectant in the film (and more preferably no humectant in the film), to thereby avoid a too wet, self-adhering film . In particular, it is preferred to formulate the film with a plasticizing agent other than glycerin, which is also a humectant and a sweetener other than sorbitol, which is a mild humectant.

Sulfur precipitating agents that reduce oral malodor may also be added to oral care films according to the present invention. These agents bind to, and inactivate, the volatile sulfur compounds that cause a large percentage of oral malodor. Precipitating agents useful in the present invention include metal salts such as copper salts and zinc salts. Preferred salts include copper gluconate, zinc citrate and zinc gluconate. The amount of sulfur precipitating agent is from about 0.01 to about 2% by weight, preferably about 0.15% by weight to about 1.5% by weight, even more preferably about 0.25% by weight to about 1.0% by weight of the film.

Saliva stimulating agents can also be added to oral care films according to the present invention. Useful saliva stimulating agents are those described in the U.S. Patent. No. 4,820,506, which is incorporated herein in its entirety, as a reference. Saliva stimulating agents include food acids such as citric, lactic, malic, succinic, ascorbic, adipic, fumaric and tartaric acids. The preferred food acids are citric, malic and ascorbic acids. The amount of saliva stimulating agents in the film is from about 0.01 to about 12% by weight, preferably about 1% by weight to about 10% by weight, even more preferably about 2.5% by weight to about 6% by weight.

Preferred plasticizing agents include triacetin in amounts ranging from about 0 to about 20% by weight, preferably about 0 to about 2% by weight. Other suitable plasticizing agents include monoacetin and diacetin.

Preferred cooling agents include monomethyl succinate, in amounts ranging from about 0.001 to about 2.0% by weight, preferably about 0.2 to about 0.4% by weight. A freshness agent containing monomethyl succinate is available from Mane, Inc. Other suitable cooling agents include WS3, WS23, Ultracool II and the like.

Preferred surfactants include the mono and diglycerides of fatty acids and esters of polyoxyethylene sorbitol, such as, Atmos 300 and Polysorbate 80. The surfactant may be added in amounts ranging from about 0.5 to about 15% by weight, preferably about 1 to about about 5% by weight of the film. Other suitable surfactants include pluronic acid, sodium lauryl sulfate and the like.

Preferred stabilizing agents include xanthan gum, locust bean gum and carrageenan, in amounts ranging from about 0 to about 10% by weight, preferably about 0.1 to about 2% by weight of the film. Other suitable stabilizing agents include guar gum and the like.

Preferred emulsifying agents include triethanolamine stearate, quaternary ammonium compounds, acacia, gelatin, lecithin, bentonite, veegum and the like, in amounts ranging from about 0 to about 5% by weight, preferably about 0.01 to about 0.7% by weight of the movie.

Preferred thickeners include methyl cellulose, carboxyl methyl cellulose and the like, in amounts ranging from about 0 to about 20% by weight, preferably about 0.01 to about 5% by weight.

Preferred thickeners include the starch, in amounts ranging from about 0 to about 10% by weight, preferably about 0.01 to about 2% by weight of the film.

Suitable sweeteners that may be included are those well known in the art, including natural and artificial ones. Suitable sweeteners include, for example: A. water-soluble sweetening agents such as monosaccharides, disaccharides and polysaccharides such as xylose, ribose, glucose (dextrose), mannose, galactose, fructose (levulose), sucrose (sugar), maltose, invert sugar (a mixture of fructose and glucose derived from sucrose), partially hydrolyzed starch, corn syrup solids, dihydrochalcones, monellin, steviosides and glycyrrhizin, B. Water-soluble artificial sweeteners such as soluble saccharin salts, eg, saccharin or calcium salts, cyclamate salts, the sodium, ammonium or calcium salt of 3,4-dihydro-6-methyl-1,2, 3- oxathiazine-4-one-2,2-dioxide, the potassium salt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-di oxide (acesulfame-K), the free acid form of saccharin and the like, C. the dipeptide-based sweeteners, such as the L-aspartic acid derivatives, such as L-aspartyl-L-phenylalanine methyl ester (aspartame) and the materials described in Pat. of E.U.A. No. 3,492,131, L-alpha-aspartyl-N- (2,2,4,4-tetramethyl-3-triethanyl) -D-alalinamide hydrate, methyl esters of L-aspartyl-L-phenylglycerin and L-aspart L-2,5, dihydrophenol glycine, L-aspartyl-2,5-dihydro-L-phenylalanine, L-aspartyl-L- (1-cyclohexyl) -alanine and the like, D. sweeteners water-soluble derivatives of naturally occurring sweeteners, such as the chlorinated derivative of common sugar (sucrose), known for example, under the brand name sucralose and E. protein-based sweeteners, such as thaumatoccous danielli (Thaumatin I and II ).

In general, an effective amount of an auxiliary sweetener is used to provide the desired level of sweetness for a particular composition and this will vary according to the selected sweetener. Typically, this amount will be from 0.01% to about 10% by weight of the composition when an easily extractable sweetener is used. The water-soluble sweeteners described in the above-mentioned category A are usually used in amounts from about 0.01 to about 10% by weight and preferably in amounts from about 2 to about 5% by weight. Some of the sweeteners of category A (for example, glycyrrhizin) may be used in the amounts established for the subsequent B-E categories due to the known sweetening ability of such sweeteners. In contrast, the sweeteners described in the BE categories are generally used in amounts from about 0.01 to about 10% by weight, with about 2 to about 8% by weight being preferred and from about 3 to about 6% by weight being more preferred . Said amounts can be used to achieve the desired level of sweetness regardless of the level of flavor achieved with any of the optional flavor oils used. Of course, sweeteners do not need to be added to non-oral administration films.

Flavors that can be used include those known to those skilled in the art, such as natural and artificial flavors. Said flavorings may be chosen from synthetic flavor oils and aromatic flavors and / or oils, oilseins and extracts derived from plants, leaves, flowers, fruits, etc., and combinations thereof. Representative flavor oils include: peppermint oil, cinnamon oil, peppermint oil, clove oil (spice), bay oil, thyme oil, cedar leaf oil, oil nutmeg, sage oil and bitter almond oil. Also useful are artificial, natural or synthetic fruit flavorings, such as vanilla, chocolate, coffee, cocoa oil and citrus fruits; including oil of lemon, orange, grape, lime and grapefruit and fruit essences including apple, pear, peach, strawberry, raspberry, cherry, plum, apricot, etc. Said flavorings can be used individually or in a mixture. The commonly used flavors include mints, such as peppermint, artificial vanilla, cinnamon derivatives and various fruit flavors, which can also be used individually or in a mixture. Similarly, flavorings such as aldehydes and esters can be used, including cinnamyl acetate, cinnamaldehyde, citral, diethylacetal, dihydrocarvyl acetate, eugenil format, p-methylanisole, etc. In general, any flavor or food additive may be used, such as those described in Chemicals Used in Food Processing, publication 1274 by The National Academy of Sciences, pages 63-258. Further examples of aldehyde based flavors include but are not limited to, acetaldehyde (apple), benzaldehyde (cherry, almond), cinnamic aldehyde (cinnamon), citral, eg, alpha citral (lemon, lime), neral, for example , beta ciitral (lemon, lime), decanal (orange, lemon), vanillin ethyl (vanilla, cream), heliotropin, for example, piperonal (vanilla, cream), vanillin (vanilla, cream), alpha-amyl cinnamaldehyde (fruit flavors) -species), butyraldehyde (butter, cheese), varaldehyde (butter, cheese), citronella (to modify, various types), decanal (citrus fruits), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits) , aldehyde C-12 (citrus fruits), 2-ethyl-butyraldehyde (grain fruits), tolyl aldehyde (cherry, almond), veratraldehyde (vanilla), 2,6-dimethyl-5-heptenal, for example, melon (melon) ), 2-6-dimethyloctanal (green fruit) and 2-dodecenal (citrus, tangerine), cherry, grape, mixtures thereof and the like.

The amount of flavorant used is normally a matter of preference, subject to factors such as the type of flavor, the individual taste and the desired intensity of flavor. Thus, the quantity can be varied to obtain the desired result in the final product. Such variations are within the capabilities of those skilled in the art without the need for experimentation. In general, amounts of about 0.1 to about 30% by weight are usable with preferred amounts of about 2 to about 25% by weight and more preferred amounts of about 8 to about 10% by weight.

The compositions of this invention may also contain coloring or coloring agents. The coloring agents are used in effective amounts to produce the desired color. Coloring agents useful in the present invention include pigments such as titanium dioxide, which may be incorporated in amounts of up to about 5% by weight and preferably less than about 1% by weight. The colorants can also include natural food colors and dyes suitable for food, drugs and cosmetic applications. These dyes are known as dyes and lacquers FD &; C. Acceptable materials for the foregoing spectrum of use are preferably water soluble and include Blue No. 2 FD &C, which is the disodium salt of 5,5-indigotinedisulfonic acid. Similarly, the dye known as Green No. 3 comprises a triphenylmethane dye and is the monosodium salt of 4- [4-N-ethyl-p-sulfobenzylamino) diphenylmethylene] - [1-N-ethyl-Np-sulfonium benzyl] ) -2,5-cyclohexanedienimine]. A complete list of all FD &C and D &C dyes and their corresponding chemical structures can be found in the Kirk-Othmer Encyclopedia of Chemical Technology, Volume 5, Pages 857-884, the text of which is incorporated herein by reference.

Antimicrobial Efficacy of Oral Care Films The preferred embodiment of the oral care film composition according to the present invention contains the essential oils used in the LISTERINE® mouth rinse to provide antimicrobial efficacy. The films are manufactured and sized to be placed in the oral cavity. The film adheres to a surface in the mouth, usually the palate or tongue and dissolves quickly. The amount of essential oils in a single film that is of a preferred size to be placed in the mouth is significantly less than the recommended amount of 20 ml of LISTERINE® mouthwash.

In a preferred formula according to the present invention, the amount of thymol and eucalyptol in the films is about 70 times less than in the mouthwash. The amount of methyl salicylate in the film is approximately 46 times less than in the rinse. The amount of menthol in the film is about 2.8 times less than in the mouthwash. These figures are based on the comparison of a 20 ml dose of liquid mouthwash with a film of 0.0358 grams.

The film of the present invention provides sustained antimicrobial efficacy to said low amounts of oils. It is considered that the effectiveness of essential oils is improved by creating a layer of pullulan that supports essential oils in the oral cavity. This is unexpected because pullulan is soluble in water and the film dissolves rapidly.

The increased antimicrobial activity is shown in the following experiments.

The purpose of these experiments was to determine the antibacterial efficacy of an application of the film on the tongue, against the microorganisms that cause bad breath, thirty, sixty or ninety minutes after using it. The thirty minute study also proved the effectiveness of using two films. The recoverable accounts of the microbial oral malodor in the subjects of the experiment were determined by the seeding of microorganisms recovered with an agaric tongue on a selective medium of agar. The test product was distributed and the subjects dissolved in their language one or two films for the breath. The subjects remained under the premises of the experiment and returned for a second abate languages in thirty, sixty or ninety minutes after placing the test product in their language. After the forty-eight hour bleaching period, the subjects returned for a control without treatment.

The group that used a single film for thirty minutes showed a logarithmic reduction in its malodorous microbial score, compared to the control group. The data were at the statistically significant limit (p = 0.052). The difference between the group of a film and the control group without treatment represented a reduction of 42.7% in the counting of microbial colonies of bad odor.

The microbial reduction of the statistically significant malodor was also observed with the group that used two films. A reduction of 79.6% was obtained in the counting of microbial colonies of bad odor (p <0.001).

The microbial reduction of the statistically significant malodor was observed sixty minutes after using a single film for the breath. A reduction of 69.8% was obtained in the counting of microbial colonies of bad odor (p = 0.002).

A significant reduction in odor was also observed ninety minutes after using a single film for the breath. A reduction of 69.1% was obtained in the counting of microbial colonies of bad odor (p = 0.006).

The data from these studies support the following conclusions: (1) The breath film based on the pullulan polymer containing essential oils, is an antibacterial composition effective against the bad smell caused by bacteria and (2) thirty, sixty and ninety minutes after using it, significant bacterial reductions were achieved in vivo.

Experimental procedures The procedures used in said antimicrobial studies were as follows. Subjects were asked to refrain from all oral hygiene procedures (for example, brushing teeth, oral washing), eating or drinking any food, drink or candy from midnight before the study and until the completion of the study, at each day of the experiment. The subjects abstained from smoking on the mornings prior to the odor evaluations.

Test of Annihilation of Germs In vivo 1. Materials Test tubes containing 10 ml of 0.01% sterile peptone Abate sterile tongues OOPS lll Agar (B.-F. Turng, GE Minah, and WA Falkler.Development of an Agar Medium for Detection of Oral H2S-producing Organisms. Res 76 IADR Abstracts 1997.): Base of Columbia Agar (Catalog # DF0792-17-3) 44 grams Distilled Water 1 liter Lead Aetate3 (Sigma L3396) 0.2 grams Heminb Solution (Sigma H-1652) 2 ml Glutathione0 (Sigma G4251) 1.2 grams Forty-four grams of Base of Columbia agar was suspended in 1 liter of distilled water and boiled until complete dissolution. The medium was sterilized at 121-124 ° C for 15 minutes. a O.2 grams of lead acetate were dissolved in 1 ml of distilled H2O, the solution was filtered and sterilized. They were added after sterilization of the basic medium in an autoclave. b 50 mg of hemin was dissolved in 1 ml of 1 N NaOH, completing 100 ml with distilled H2O. The solution was filtered and sterilized. 2 ml per liter of OOPS III was added after sterilization of the basic medium in an autoclave. c 1.2 grams of glutathione was dissolved in 10 ml of distilled H2O. The solution was filtered and sterilized. They were added after sterilization of the basic medium in an autoclave. 2. Procedure a. All media were pre-reduced in an anaerobic chamber. The plates were loose wrapped in plastic bags to prevent excessive drying. b. The panelists refrained from oral hygiene, eating and drinking from midnight before the test and until the test was completed. Twelve panelists were used for the sixty and ninety minute experiments. Eighteen panelists were used for the thirty-minute experiments. c. Each panelist rubbed the right side of his tongue with a tongue abbe, placing it at the midpoint of it and beating the abbe tongue with the tip forward. The abate tongues was placed in a peptone tube. d. Panelists who received a film treatment, single or double, placed the breath film on the left side of their tongue, covering it from the midpoint to the tip and letting the film dissolve by slightly opening the mouth for thirty. seconds to prevent the adherence of this to the palate. and. After thirty or sixty minutes, the panelists rubbed the tongue on the left side of their tongue, placing the tongue at the midpoint of the tongue and striking the tip forward. The abate tongues were placed in a peptone tube. F. The peptone tubes were vigorously shaken for 10 seconds and serial dilutions were made. The 10"4 dilution was plated in duplicate on OOPS III Agar using a Spiral Biotech Autopyte 4000 (Bethesda, MD) All plates were identified with the subject's initials, test date, sampling time station and number duplicate. i. g. The plates were incubated in an anaerobic chamber at 35-37 ° C for 7 days to allow complete development of the colonies without excess growth. h. After a 48-hour washout period, panelists 5 returned to the control without treatment. No film was applied and steps (e) and (g) were followed as described above. i. After a 48-hour washout period, sixty-minute panelists returned for another one-film application. Steps (a) and (h) were followed, except that the panelists returned to stage e, after 90 minutes. j. The dark pigmented colonies (organisms that produce H2S) were counted by hand, as whole plate counts, under appropriate amplification or by Segment counts using a Spiral Biotech counting gauge. The appropriate code was established based on the data sheet to allow the interpretation of the counts. The counted CFUs were converted to CFU / ml by dividing by the appropriate volume exponential constant listed in Table A and multiplying by 1000. Subsequently that value was multiplied by a plate dilution factor (104). 20 Table A. Exponential Volume Constants for Peer Segments The film used in the germ annihilation tests in vivo was that of Example 19 as described in Table 2. The films used in the study were approximately 22 mm x 32 mm, between approximately 0.003 and 0.004 cm in thickness and weighed between approximately 35 to approximately 37 mg.

The enhanced activity of the pullulan film containing the essential oil is also shown in Figures 1 and 2. Figure 1 is a photograph of an agar plate extension with Streptococcus mutans, ATCC # 25175, to which was added a portion of pullulan film containing an essential oil according to the present invention. The film portion released approximately 0.391 mg of essential oils using Example 15 listed below.

Figure 2 is a photograph of an agar plate extension with Streptococcus mutans, ATCC # 25175 to which a few drops of essential oils were added. The drops were 148 ul in volume and contained 0.391 mg of essential oils. The percentages of each essential oil in the drops are 2,200% menthol, 0.186% eucalyptol, 0.186% methyl salicylate and 0.1300% thymol in a hydroalcoholic solution.

The area or zone of inhibition around the film in Figure 1 is much greater than the dimensions of the film. This is due to the presence of the puluano, since the oils in the film were dispersed outwards and were not washed after repeated rinsings. In contrast, the essential oils in Figure 2 did not diffuse away from the drop, remained as a circle and easily washed after two rinses. This shows that the antimicrobial efficacy of essential oils is enhanced by the presence of pullulan.

Methods for Preparing the Films Containing the Essential Oil The methods for preparing the films according to the invention are capable of encapsulating the oil within the film-forming matrix and maintaining the integrity of the film, even when the film contains oils in the film. amounts of 10% or more.

In certain methods for preparing the films according to the invention, the film-forming ingredients are mixed and hydrated with water by separating the water-soluble ingredients, which are mixed in an aqueous solution also separated from the organic ingredients and the surfactants. In such methods, the final formulation is preferably produced by mixing the film-forming phase with the aqueous phase, then mixing with the organic phase, which incubates the surfactants, such as Polysorbate 80 and Atmos 300. This mass is mixed until emulsification. In other embodiments, the aqueous phases and the film-forming phases are combined in a single phase by dissolving the water-soluble ingredients and subsequently adding the gums to hydrate them. The organic phase is then added to this single aqueous phase.

The resulting formulation is emptied onto a suitable substrate and dried to form the film. Preferably, the film is dried with air or under hot air and cut to the desired dimension, packaged and stored. The film may contain a moisture of from about 0.1% to about 10%, by weight, preferably a moisture of from about 3% to about 8%, by weight, even more preferably a moisture of from about 4% to about 7%, by weight.

The film-forming phase may include pullulan and stabilizing agents such as xanthan gum, locust bean gum and carrageenan. Said ingredients are mixed and subsequently hydrated with water for about 30 to about 48 hours to form a gel. Preferably, the water is heated to a temperature of about 25 to about 45 ° C to promote hydration. The amount of water is approximately 40 to 80% of the gel. Then, the resulting hydrated gel is cooled to a temperature of about 20 to about 30 ° C for about 1 to about 48 hours. Preferably, the water is de-ionized.

The aqueous phase may include ingredients such as coloring agents, copper gluconate and sweetener. Preferably, the water is de-ionized and the amount used the is from about 5% to about 80% by weight, of the final gel mixture.

If sodium saccharin and copper gluconate are ingredients of the formulation, it is preferable to dissolve them separately in the solution to avoid their precipitation.

In a preferred production method for the manufacture of the films containing essential oil according to the invention, it is possible to hydrate the film-forming ingredients and combine all the ingredients without heating. The preferred method comprises dissolving the water-soluble ingredients in water to form an aqueous mixture, mixing the powdered film-forming ingredients, to form a powder mixture, adding the powder mixture to the aqueous mixture to form a hydrated polymer gel, stir the hydrated polymer at room temperature for about 30 minutes to about 48 hours, mixing the freshness agent, thymol and menthol in the flavor oil to form a mixture in oil, add methyl salicylate, eucalyptol and the surfactants to the mixture in oil, add the mixture in oil to the hydrated polymer gel and mix until uniform, deaerate the film until the air bubbles are removed, empty the uniform mixture on an appropriate substrate and dry the pouring mixture to form a film.

The preferred method for making a film containing an essential oil, hydrates the film-forming ingredients without heating the water. The heating of the ingredients increases the energy costs of the manufacturing process. In addition, the heating results in the undesirable loss by evaporation of the volatile ingredients; which affects the activity of annihilation of the germs of the composition due to the loss of essential oils. In addition, mixing the oils in two stages decreases the amount of flavor lost.

Although linking to other theories is not desired, it is believed that film-forming ingredients can be hydrated and mixed without heating due to an ionic effect known as Donan equilibrium. The hydration of the film-forming agents in the presence of the electrolytes in the solution effectively decreases the viscosity of the polymeric gel that is being formed, thereby increasing the efficiency of the hydration process. The water-soluble formulation ingredients provide the electrolytes that are dissolved in the hydration solution prior to the addition of the film-forming ingredients. The high-cut mixing also accelerates hydration, which breaks up the agglomeration of the powders, providing a greater surface area for contact with water. Additionally, the effects of local heating, generated in the cutting regions, provide energy for hydration without substantially increasing the temperature of the dough. It is preferable to avoid adding copper gluconate and saccharin to the aqueous solution at the same time, since a precipitate will form. Therefore, it is preferred to combine sweeteners, rather than saccharin with copper gluconate.

Description of Film Compositions Releasing Pharmaceutical Agents A second embodiment of the invention is a fast dissolving film that includes at least one physiologically acceptable and pharmaceutically active agent. The term "physiologically acceptable" as used herein, is intended to encompass compounds which, after administration to a patient, are suitably tolerated without causing negative side effects. The expression encompasses edible compounds.

The term "pharmaceutically active agents" as used herein, is intended to encompass agents other than foodstuffs, that promote a structural and / or functional change in the bodies in which they have been administered. Said agents are not particularly limited, however, they must be physiologically acceptable and must be compatible with the film. Suitable pharmaceutically active agents include, but are not limited to: A. antimicrobial agents, such as triclosan, cetyl pyridium chloride, domifen bromide, quaternary ammonium salts, zinc compounds, sanguinarine, fluorides, alexidine, octonidine, EDTA and the like, B. non-steroidal anti-inflammatory drugs, such as aspirin, acetaminophen, ibuprofen, ketoprofen, diflunisal, calcium phenoprofen, naproxen, sodium tolmetin, indometasin and the like, C. anti-tusivos, such as benzonatato, caramifen edisilato, menthol, dextromethorphan hydrobromide, clofedianol hydrochloride and the like, D. decongestants, such as pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine, pseudoephedrine sulfate and the like , E. antihistamines, such as brompheniramine maleate, chlorpheniramine maleate, carbinoxamine maleate, clemastine fumarate, dextr maleate lorfeniramine, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, azatadine maleate, diphenhydramine citrate, doxylamine succinate, promethazine hydrochloride, pyrilamine maleate, tripelenamine citrate, triprolidine hydrochloride, acrivastine, loratadine, brompheniramine, dexbromfeniramine and the like, F. expectorants, such as guaifenesin, ipecac, potassium iodide, terpine hydrate, and the like, G. anti-diarrheals, such as loperamide and the like, H2-antagonists, such as famotidine, ranitidine and similar, I. proton pump inhibitors, such as omeprazole, lanzoprasol and the like, non-selective general CNS depressants, such as aliphatic alcohols, barbiturates and the like, non-selective general CNS stimulants, such as caffeine, nicotine, strinin, picrotoxy, pentylenetetrazol and the like, L. drugs that selectively modify CNS function such as phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide, metosuximide, fensuximide, trimethadione, diazepam, benzodiazepines, phenacemide, pheneturide, acetasolamide, sultiam, bromide and the like, M. anti-parkinsonism drugs such as levodopa, amantidine and the like, N. narcotic analgesics such as morphine, heroin, hydromorphone, metopon, oxymorphone, levorphanol, codeine, hydrocodone, xycodone, nalorphine, naloxone and the like, O. antipyretics-analgesics such as salicylates, phenylbutazone, indomethacin, phenacetin and the like, P. Psychopharmacological drugs such as chlorpromazine, methotrimeprazine, haloperidol, clozapine, reserpine, imipramine, tranylcypromine, phenelzine, lithium and the like.

The amount of medicament that can be used in fast dissolving films according to the present invention depends on the dose necessary to provide an effective amount of the medicament. Examples of doses for specific drugs that can be released by a rapid dissolution oral film tape are reviewed in Table 1. TABLE 1 The ingredients used to make the films containing the pharmaceutical agents are similar to those used to make the oral care films. Specifically, the plasticizing agents, the cooling agents, the surfactants, the stabilizing agents, the emulsifiers, the thickening agents, the binding agents, the film formers, the sweeteners, the flavors and the colors described above can also be used in all the films according to the present invention.

Films that release a pharmaceutical agent may also include a triglyceride. Examples of triglycerides include vegetable oils such as corn oil, sunflower oil, peanut oil, olive oil, canola oil, soybean oil and mixtures thereof. A preferred triglyceride is olive oil. The triglyceride is added to the film in amounts from about 0.01% by weight to about 12% by weight, preferably in a range from about 0.5% by weight to about 9% by weight of the film.

Films containing pharmaceutical agents may also include a condom. The condom is added in amounts of from about 0.001% by weight to about 5% by weight, preferably from about 0.01% by weight to about 1% by weight of the film. Preferred condoms include sodium benzoate and potassium sorbate.

Films containing a pharmaceutical agent can also include a polyethylene oxide compound. The molecular weight of the polyethylene oxide is from about 50,000 to about 6,000,000. A preferred polyethylene oxide is N-10 available from the Union Carbide Corporation. The polyethylene oxide is added in amounts of from about 0.1% to about 5% by weight, preferably from about 0.2% by weight to about 4.0% by weight of the film.

Films containing a pharmaceutical agent may also include propylene glycol. The propylene glycol is added in amounts of from about 1% by weight to about 20% by weight, preferably from about 5% by weight to about 15% by weight of the film.

The active ingredient used in the film may be coated to mask the taste thereof or to prevent the active ingredient from numbing the tongue or other surfaces of the oral cavity. The coatings that may be used are those well known to those skilled in the art. These include polymers such as Eudragit® E, cellulosic polymers such as ethylcellulose and the like.

A further way of masking the flavor of the active ingredient is to use an ion exchange resin such as Amberlite RP-69, available from Rohm and Haas and the Dow XYS-40010.00 available from Dow Chemical Co.

Examples The invention will be illustrated in more detail with reference to the following Examples, but it should be understood that the present invention is not limited thereto.

Preparation of Method 1 The following method was used to prepare the films of Examples 1-13. A. Film-forming ingredients (eg, xanthan gum, locust bean gum, carrageenan, and pullulan) other than Polysorbate 80 and Atmos 300 were mixed and hydrated in purified hot water to form a gel that was stored in a refrigerator overnight at a temperature of about 40 ° C to form the AB preparation. The coloring agents, the copper gluconate and the sweetener was added and dissolved in purified water to form preparation BC Preparation B was added to preparation A and mixed thoroughly to form the CD preparation Flavoring agent and oils (eg, the freshness agent, thymol, methyl salicylate, eucalyptol and menthol) were mixed to form the preparation. The Polysorbate 80 and the Atmos 300 were added to preparation D and mixed thoroughly to form the preparation EF. Preparation E was added to preparation C and they were mixed perfectly to form the FG preparation. The F preparation was poured into a mold to form a sp desired at room temperature. The film was dried under hot air and cut to the desired dimension, packed and stored.

Preparation of Method II Examples 14-18 were prepared using a preferred method, comprising the following steps: A. dissolving copper gluconate, acelsulfame K, aspartame, glycerin, sorbitol and dye in purified water to form an aqueous mixture, B. Mix the pullulan, the xanthan gum, the locust bean gum and the carrageenan powder together to form a powder mixture, C. add the powder mixture from step B to the aqueous mixture from step A to forming a hydrated polymer gel, D. stirring the hydrated polymer from step C at low speed (approximately 50-100 RPM) overnight at room temperature, E. mixing and dissolving the freshness agent, thymol and menthol at the flavoring oil, F. add methyl salicylate, eucalyptol, Polysorbate 80 and Atrnos 300 to the oil mixture of stage E, G. add the mixture in oil from stage F to the hydrated polymer gel of the stage D and mix until uniform, H. v Add the uniform mixture of step G in a suitable container, I. Dry the mixture to form a film.

Example 1 Example 1 produced a bluish-green, mint-flavored, and refreshing menthol-flavored film according to the invention.

Examples 2-4 Examples 2-4 contain sorbitol, glycerin or both. These examples gave products of easily breakable portions, or were too wet and / or self-adhering. However, they produced rapidly dissolved films in the oral cavity with a refreshing menthol flavor.

Examples 5-6 Examples 5-6 did not contain glycerin or sorbitol. The resulting films did not stick during processing and packaging and were more moisture stable for a long time.

Examples 7-9 Examples 7-9 were produced to determine the effect of Avicel® on the killing activity of germs. While examples 7-9 produced more acceptable films from a processing and handling perspective, they had lower antimicrobial activity relative to films without Avicel®, as Example 8.

Example 10-15 Examples 10-15 varied the amounts of aspartame and menthol to alter the sweetening and freshness of the film.

Example 16 Example 16 was prepared by replacing sorbitol with maltitol, which has less wetting properties. The resulting film was less sticky during processing and long-term storage.

Example 17 In Example 17 the pullulan was replaced with another film former, polyvinyl pyrrolidone, to produce films according to the invention.

Example 18 Example 18 was prepared by partially replacing pullulan with another film former, konjac gum, to produce films according to the invention.

Example 19 Example 19 represents a film containing a salivary stimulant, citric acid.

Example 20 Example 20 is the film composition used in the antimicrobial efficacy studies described above.

The formulas of examples 1-20 are summarized in Table 2. The amounts in said examples have the effective weight (grams) or% weight / weight. These formulas create the solution / gel that is emptied and dried in a film. The effective amount of each ingredient in the finished dry film depends on the amount of relative humidity removed during drying.

Table 2 Table 2 cont.

The following examples are films according to the second embodiment of the present invention, in which the fast dissolving film contains a pharmaceutical agent. Examples 21A-21 E, listed in Table 3, are medicaments containing rapidly dissolving oral film formulations. The amounts in Table 3 are in milligrams.

TABLE 3 'Calculated assuming the total evaporation of water from the films after drying.

The Table summarizes the data of the additional films according to the present invention. The amounts in Table 4 are in% w / w before drying.

TABLE 4 Example 22A was used to make films containing a) 7.5 mg of dextromethorphan hydrobromide, b) 2.5 mg of tripolidine, c) 4.0 mg of chlorpheniramine maleate and d) 12.5 mg of diphenhydramine hydrochloride.

Example 22B was used to make a film containing 10 mg of dextromethorphan hydrobromide.

Example 22C was used to make a film containing 10 mg of dextromethorphan hydrobromide.

Example 22D was used to make a film containing a) 10 mg of phenylephrine hydrochloride, b) 10 mg of phenylephrine hydrochloride and 4 mg of chlorpheniramine maleate and c) 10 mg of dextromethorphan hydrobromide.

Example 22E was used to make a film containing 7.5 mg of dextromethorphan hydrobromide.

Example 22F was used to make a film containing 20 mg of coated dextromethorphan hydrobromide to provide a dose of 7.5 mg.

Example 22G was used to make a film containing a) 7.5 mg of dextromethorphan hydrobromide, b) 10 mg of phenylephrine hydrochloride and c) 10 mg of phenylephrine hydrochloride and 4 mg of chlorpheniramine maleate Example 22H was used to make a film containing 15 mg of dextromethorphan hydrobromide.

Example 221 was used to use a film containing 15 mg of dextromethorphan hydrobromide.

Processes for the Manufacture of Films that contain a Pharmaceutical Agent.

Example 22A was made using the following procedure. 1. Add sodium benzoate and sweeteners to water. 2. Mix carob gum, xanthan gum and carrageenan together.

Add the rubber mixture to the mixture from stage 1 and mix until dissolved. Mix the active ingredient with water or propylene glycol. Heat if necessary. Add the remaining ingredients to the mixture from step 4 or mix them in a separate mixture. Add the mixtures from stage 4 and 5 to the mixture from stage 3. Empty and dry to make a film and cut to a specific size to achieve the desired dose.

Examples 22B-22E were made using the following procedure. Add sodium benzoate to water heated to 50 ° C. Mix to dissolve. Separately, add Peg 1450, titanium dioxide and active ingredient to the mixture from step 1, mixing with each addition. Mix carob gum, xanthan gum and carrageenan together. Add the gums to the mixture from stage 2 and mix until dissolved. Add the remaining ingredients together with heating if necessary. Add the mixture of stages 4 and 5 together. Empty and dry to make a film and cut to a specific size to achieve the desired dose.

Examples 22F-22I were made in the same manner as examples 20B-20E, except that the active ingredient was perfectly dispersed before the film was emptied.

While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope thereof.

Claims (47)

1. CLAIMS An edible film adapted to adhere to and dissolve in the mouth of a consumer, wherein said film comprises at least one water-soluble polymer and an antimicrobial effective amount of at least one essential oil selected from the group consisting of thymol, methyl salicylate. , eucalyptol and menthol.
2. The edible film according to claim 1, comprising at least two of said essential oils.
3. The edible film according to claim 1, comprising at least three of said essential oils.
4. The edible film according to claim 1, comprising thymol, methyl salicylate, eucalyptol and menthol.
5. The edible film according to claim 4, further comprising a gluconic acid salt.
6. The edible film according to claim 4, further comprising copper gluconate.
7. The edible film according to claim 1, wherein said water soluble polymer is selected from the group consisting of pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, tragacanth gum, guar gum, acacia gum, gum arabic, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, quitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, isolated soy protein, isolated whey protein, casein and mixtures thereof.
8. The edible film according to claim 7, wherein said water-soluble polymer is pullulan.
9. The edible film according to claim 8, which comprises from about 40 to about 80% by weight, of pullulan, from about 0.01 to about 4% by weight, of thymol, from about 0.01 to about 4% by weight, of salicylate of methyl, from about 0.01 to about 4% by weight, of eucalyptol and from about 0.01 to about 15% by weight of menthol.
10. The edible film according to claim 7, further comprising: from about 0.01 to about 5% by weight, of at least one stabilizing agent, from about 0.001 to about 0.01% by weight, of at least one coloring agent, from about 0.1 to about 8% by weight, of water, from about 0.01 to about 15% by weight, of at least one sweetening agent, from about 0.1 to about 15% by weight, of at least one flavoring agent, from about 0.1 to about 4% by weight, of at least one freshness agent and from about 0.1 to about 5% by weight, of at least one surfactant.
11. The edible film according to claim 10, wherein said at least one stabilizing agent is selected from the group consisting of xanthan gum, locust bean gum and carrageenan and said at least one sweetening agent is selected from the group consisting of saccharin, aspartame and acesulfame K.
12. The edible film according to claim 1, wherein said film is not substantially self-adhesive.
13. The edible film according to claim 1, wherein said film is free of glycerin and sorbitol.
14. The edible film according to claim 1, wherein said film is free of humectants.
15. The edible film according to claim 1, wherein said essential oils comprise at least about 10% by weight of the film.
16. The edible film according to claim 15, wherein the essential oils comprise at least about 15% by weight of the film.
17. The edible film according to claim 1, further comprising water in an amount from about 3% by weight to 8% by weight.
18. A method for preparing a physiologically compatible film, said method comprises: mixing at least one water-soluble film former and at least one stabilizing agent to provide a film-forming mixture, dissolving the soluble ingredients in water to provide an aqueous solution, combining said film-forming mixture and said aqueous solution to provide a gel hydrated polymer, mixing the oils to form a mixture in oil, adding said oil mixture to said hydrated polymer gel and mixing to give a uniform gel, emptying the uniform gel on a substrate and drying the drained gel to provide said film.
19. The method according to claim 18, wherein said at least one surfactant is mixed with said mixture in oil.
20. The method according to claim 18, wherein the total amount of said oils in said mixture in oil is at least about 5% by weight, of the total weight of the ingredients in said method.
21. 21. The method according to claim 20, wherein said total amount of oil is at least 15% by weight.
22. 22. The method according to claim 18, wherein said drying is carried out until said film has a moisture content from about 3% by weight, to about 8% by weight.
23. 23. The method according to claim 18, wherein, before being combined with said aqueous solution, said film-forming mixture is hydrated with water at a temperature of about 25 to about 50 ° C and subsequently cooled to a temperature of about 4. up to about 30 ° C for about 2 to 48 hours.
24. 24. The method according to claim 18, wherein said film-forming mixture is a powder, which is directly combined with said aqueous solution.
25. 25. The method according to claim 24, wherein said hydrated polymer gel is formed without heating.
26. 26. The method according to claim 25, wherein said hydrated polymer gel is stirred at room temperature for about 2 to about 48 hours.
27. The method according to claim 26, wherein said oil mixture is prepared by mixing thymol and menthol in a flavor oil and subsequently adding methyl salicylate and eucalyptol.
28. A non-self-adhering film produced in accordance with the method of claim 18.
29. The method according to claim 18, wherein the water-soluble film former is selected from the group consisting of pullulan, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol. , edge gum rubber, guar gum, acacia gum, gum arabic, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, isolated soy protein, isolated whey protein, casein mixtures thereof.
30. The method according to claim 29, wherein said water-soluble polymer is pullulan.
31. 31. An edible film adapted to dissolve in the mouth of a consumer, wherein said film comprises a single layer that includes the pullulan of at least one pharmaceutical agent.
32. 32. The edible film according to claim 31, wherein said pharmaceutical agent is selected from the group consisting of microbial agents, non-steroidal antiinflammatory agents, antitussives, decongestants, antihistamines, expectorants, anti-diarrheals, H2-antagonists, the proton pump, agents of the central nervous system and mixtures thereof.
33. 33. The edible film according to claim 32, wherein the microbial agent is selected from the group consisting of triclosan, cetyl pyridium chloride, domifen bromide, quaternary ammonium salts, zinc compounds, sanguinarine, fluorides, alexidine, octonidine, EDTA and mixtures thereof.
34. 34. The edible film according to claim 32, wherein the non-steroidal anti-inflammatory agent is selected from the group consisting of aspirin, acetaminophen, buprofen, diflunisal, calcium phenoprofen, naproxen, sodium tolmetin, indomethacin and mixtures thereof.
35. 35. The edible film according to claim 32, wherein the anti-tusive is selected from the group consisting of benzonatate, caramifen edisylate, dextromethorphan hydrobromide, chlophedianol hydrochloride and mixtures thereof.
36. 36. The edible film according to claim 32, wherein the decongestant is selected from the group consisting of pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine and mixtures thereof.
37. 37. The edible film according to claim 32, wherein the anti-histamine is selected from the group consisting of brompheniramine maleate, chlorpheniramine maleate, carbinoxamine maleate, clemastine fumarate, dischlorpheniramine maleate, diphenhydramine hydrochloride, diphenhydramine citrate, diphenylpyraline hydrochloride, doxylamine succinate, promethazine hydrochloride, pyrilamine maleate, tripelenamine citrate, triprolidine hydrochloride and mixtures thereof.
38. 38. The edible film according to claim 32, wherein it is expectorant is selected from the group consisting of guaifenesin, ipecac, potassium iodide, terpin hydrate and mixtures thereof.
39. The edible film according to claim 32, wherein the anti-d-arreic is loperamide.
40. The edible film according to claim 32, wherein the H2-antagonist is selected from the group consisting of famotidine, raditidine and mixtures thereof.
41. The edible film according to claim 32, wherein the proton pump inhibitor is selected from the group consisting of omeprasol, sunflower and mixtures thereof.
42. A method for releasing and improving the retention of an effective amount of a microbial agent in the oral cavity comprising introducing the oral cavity of a fast dissolving film comprising pullulan and a microbial agent comprising menthol and at least one of methyl salicylate , eucalyptol and thymol, wherein said pullulan improves retention of the microbial agent in the oral cavity.
43. The method according to claim 42, wherein the microbial agent comprises menthol, methyl salicylate, eucalyptol and thymol.
44. The method according to claim 42, wherein the amount of pullulan in the film is from about 40% by weight to about 80% by weight.
45. 45. The method according to claim 42, wherein the amount of microbial agent in the film is from about 5% by weight to about 12% by weight.
46. 46. The method according to claim 43, wherein the amount of microbial agent in the film is from about 5% by weight to about 12% by weight.
47. 47. A method for releasing and improving the retention of an effective amount of an antimicrobial agent in the oral cavity, comprising the introduction into the oral cavity of an edible film according to claim 9. fifteen twenty