A wide variety of edible compositions exist in nature, are grown, or are manufactured. One particular kind of manufactured edible compositions comprises lozenges, films, and other compositions that are intended to be placed in and to dissolve or otherwise disassociate in the mouth.
U.S. Pat. No. 4,517,173 to Kizawa et al. (1985) discloses a film that adheres to mucous membrane. The film includes at least three layers. The layers are a pharmaceutical layer, a poor water-soluble layer, and an intermediate layer.
The pharmaceutical layer is a material selected from the group consisting of predonisolone and allantoin together with water-soluble cellulose derivatives. The cellulose derivatives are selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxy propyl methyl cellulose and mixtures thereof.
The predonisolone, allantoin, and/or celluose derivatives form a thin film base. The poor water-soluble layer consists of water-soluble cellulose derivative together with water-soluble components. The water-soluble components are selected from the group consisting of shellac, higher fatty acids, and mixtures thereof. The intermediate layer consists of water-soluble cellulose derivatives not containing a pharmaceutical agent and not containing poor water soluble components.
Another embodiment of the film described in U.S. Pat. No. 4,517,173 includes one layer of pharmaceutical agents and water-soluble high polymer material. The other layer of the film consist of poor water-soluble agents. A first solvent solution for forming the pharmaceutical agent and water-soluble high polymer material first layer is prepared. A second solvent solution for forming the poor water-soluble agents second layer is prepared separately. The first solution is coated on a base plate having a favorable releasing nature. The solvent is removed from the solution to produce a first film layer on the base plate. The second solution is then coated on the first layer. The solvent is removed from the second solution. The solvent is removed from the second solution to form the second film layer.
By way of example, in U.S. Pat. No. 4,517,173 a solution for the film base agent for preparing the pharmaceutical layer is prepared by dissolving hydropropyl cellulose and macrogol-400 (polyethylene glycol) in ethyl alcohol and distilled water. The distilled water contains dissolved predonisolone. A solution for preparing the poor water-soluble layer is prepared by dissolving hydroxypropyl cellulose, magrogol, and shellac in ethyl alcohol. The solution for the first base agent for the intermediate layer is prepared by dissolving hydroxypropyl cellulose and magrogol in ethyl alcohol.
U.S. Pat. No. 5,948,430 to Zerbe et al. (1999) discloses a monolayer film formed from a mucoadhesive composition. The mucoadhesive composition comprises at least one water-soluble polymer, at least one member selected from the group consisting of a polyalcohol, a surfactant and a plasticizer; at least one cosmetic or pharmaceutically active ingredient; and a flavoring agent. The film rapidly softens and completely disintegrates in the oral environment and has a dry film thickness suitable for application in the mouth without causing adverse feeling in the mouth. During preparation of the film, the polyalcohol, surfactants, plasticizers, and possible other ingredients except the water-soluble or water-dispersible polymer(s) are dissolved in a sufficient amount of compatible solvent. The solvent can, for example, include water and/or alcohol. Once a clear solution is formed, the water-dispersible polymer or mixture of water dispersible polymers is slowly added with stirring, and heated if necessary, until a clear and homogeneous solution is formed. Active ingredients and flavors are added. The resulting solution is coated onto a suitable carrier material and dried to produce a film. The carrier material has a surface tension that allows the polymer solution to spread evenly across the intended coating width without soaking in to form a bond between the two. The carrier material can, for example, comprise non-siloconized polyethylene terephthalate film, on-siliconized kraft paper, polyethylene-impregnated kraft paper, or non-siliconized polyethylene film. The thickness of the film can vary between 5 and 200 um. Drying of the film is done in a high-temperature air-bath using a drying oven, drying tunnel, vacuum drier, or any other suitable drying equipment that does not adversely affect the active ingredient(s) or flavor of the film. A film thickness greater than 70 um is avoided so that an adverse feeling is not produced in the mouth.
U.S. Pat. No. 5,166,233 to Kuroya et al. (1992) describes a film that is applicable to the oral mucosa. The film comprises a homogeneous mixture. The homogenous mixture comprises a vinyl acetate homopolymer, an acrylic acid polymer, and a cellulose derivative capable of being dissolved in or swollen with water and a lower alcohol. The film also contains a salt or base to neutralize the acrylic acid polymer. The salt or base is present in an amount of from 0.03 to 0.2 equivalent to the acrylic acid polymer. The acrylic acid polymer and cellulose derivative are present at a weight ratio of from 1:9 to 9:1. The lower alcohol is methanol or ethanol. By the way of example, one procedure for preparing a film comprises mixing a vinyl acetate homopolymer, a carboxyvinyl polymer, and a hydroxypropyl cellulose to a 1:9 water/methanol solvent mixture to produce a film-forming composition. The film-forming composition is applied to a silicone-release paper, dried, and stripped off to obtain a 30 .mu.m thick adhesive film.
U.S. Pat. No. 5,047,244 to Sanvordeker, et al. (1991) describes a mucoadhesive carrier. The carrier allows controlled release of a therapeutic agent via mucosal tissue. The carrier is claimed as a “therapeutic dosage”. For example, in one claim the “therapeutic dosage” comprises an anhydrous but hydratable monolithic polymer matrix containing amorphous fumed silica and a therapeutic agent. The polymer matrix defines a mucoadhesive face. A water-insoluble barrier layer is secured to the polymer matrix. The barrier layer defines a non-adhesive face. The therapeutic agent is dehydroepiandrosterone. The polymer is polyethylene glycol. The polyethylene glycol has a number average molecular weight of about 4,000. The weight ratio of dehydroepiandrosterone to polyethylene glycol is about 1:4. By way of example, the polymer matrix and barrier film are prepared separately.
The polymer matrix is prepared by dissolving the therapeutic agent in polyethylene glycol. The polyethylene glycol is melted at 160 degrees F. The powder therapeutic agent is slowly added to the molten polyethyloene glycol and the glycol is stirred until the therapeutic agent is completely dissolved. The resulting composition is poured onto flat aluminum foil and allowed to solidify to form a mucosal composition. The mucosal composition is finely ground to a powder of about 60 to 80 mesh and blended with other matrix forming hydrophilic and hydrophobic excipients. Such excipients can comprise glyceryl behenate, polyvinyl alcohol, dicalcium phosphate dihydrate, hydroxypropyl cellulose and silica. Additional polyethylene glycol can be added. A granulation process utilizing an organic solvent or water can be used to prepare, dry, and obtain granules having a size in the range of 40 to 200 mesh.
The barrier film is prepared using constituents from the polymer matrix, except the barrier film does not include a therapeutic agent.
The components of the polymer matrix and barrier film are compressed together to obtain a bi-laminate mucoadhesive carrier.
U.S. Pat. No. 4,876,092 to Mizobuchi, et al. describes a sheet-shaped adhesive pharmaceutical preparation. The preparation can adhere to the oral cavity. The preparation comprises an adhesive layer and a carrier layer. The adhesive layer includes a carboxyvinyl polymer, a water-soluble methacrylic copolymer, a polyhydric alcohol, and a pharmaceutically active agent. The carrier layer is water-impermeable and water-insoluble. The carrier layer includes a pharmaceutically acceptable water-insoluble, film-forming high molecular weight compound and includes a plasticizer. The ingredients of the adhesive layer are substantially released from one side of the sheet-shaped pharmaceutical preparation. The ingredients are absorbed through the mucous membrane or teethridge to which the preparation is adhered in the oral cavity. By way of example, the adhesive layer is prepared by producing an adhesive layer mixture. The adhesive layer mixture is prepared by mixing the components for the adhesive layer in an appropriate solvent like ethyl alcohol. The resulting mixture is spread onto a release paper in a desired thickness in a conventional manner and is dried to produce a sheet-like adhesive layer. The components for the carrier layer are dissolved in an appropriate solvent to produce a carrier layer mixture. The resulting carrier layer mixture is spread onto the sheet-like adhesive layer and dried.
U.S. Patent Application U.S. 2002/0131990 to Barkalow et al. (2002) discloses a pullulan free edible film composition. The film comprises an effective amount of at least one film forming agent; an effective amount of at least one bulk filler agent; and, an effective amount of at least one plasticizing agent. By way of example, the film is produced by adding LustreClear (a composition by FMC Corporation for use as a clear coating for pharmaceutical tablets) to water to produce a coating mixture. LustreClear contains microcrystalline cellulose, carrageenan, polyethylene glycol, hydroxyethyl cellulose and maltodextrin. The coating mixture is heated to 50 degrees C. and other ingredients are added. While the mixture is warm, the mixture is poured onto a glass plate and drawn down to form a thin film with a 0.08 inch blade. The resulting film composition is dried at 50 degrees C. for about fifteen minutes.
U.S. Patent Application U.S. 2001/0022964 to Leung et al. (2001) discloses a consumable film. The film is adapted to adhere to and dissolve in a mouth of a consumer. The 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. By way of example, a film is prepared as follows. Xanthan gum, locust bean gum, carrageenan and pullulan are mixed and hydrated in hot purified water to form a gel. The gel is stored in a refrigerator overnight at a temperature of approximately four degrees C. to form preparation A. Coloring agents, copper gluconate, and sweetener are added to and dissolved in purified water to form preparation B. Preparation B is mixed with preparation A to form preparation C. Flavoring agents and oils (including cooling agent, thymol, methyl salicylate, eucalyptol and menthol) are mixed to form preparation D. Polysorbate 80 and Atmos 300 are added to preparation D and mixed to form preparation E. Preparation E is added to preparation C and mixed to form preparation F. Preparation F is poured on a mold and cast to form a film of desired thickness at room temperature. The film is dried under warm air.
The prior art edible films and production processes each have desirable aspects. They also have disadvantages. One disadvantage is that the prior art processes may expose medicants or actives or other compositions to water or another liquid during production of the edible films. Many medicants or other compositions are unstable in the presence of water or other liquids. A second disadvantage of prior art processes is that the production process may subject a medicant or other composition to shear. Shear can damage the medicant. Shear occurs when a mixing blade or other member forces a medicant particle intermediate the blade and another solid member, generating friction and heat. A third disadvantage of prior art processes is that they may require the application of heat at temperatures or over extended periods of time that can degrade or undesirably alter the stability or properties of a medicant or other composition. A fourth potential disadvantage of prior art processes is that they may not permit, with minimal effort, the dissolution rate of a medicant or other composition to be varied. A fifth potential disadvantage of prior art processes is that they may make use of a hydrophilic component at higher concentrations impractical because during production the hydrophilic component rapidly absorbs water and become difficult to process. A sixth potential disadvantage of prior art processes is that the edible films produced are primarily suitable only for use in the oral cavity and not for use on living cells. A seventh potential disadvantage of prior art processes is that heat alone can not, practically speaking, be used to form a smooth coating on an edible film. An eighth potential disadvantage of prior art processes is that they require the use of a solvent to produce a layer including a medicant or other desired composition. A ninth potential disadvantage of the prior art processes is that they require the compatibility of a medicant with other components in a solvent solution to be taken into account.
Accordingly, it would be highly desirable to provide an improved edible film and process for making the same that would minimize the risk that a medicant or other composition is degraded or otherwise damaged by heat, shear, or moisture; that would permit the dissolution rate of a medicant to be readily varied, that would permit the ready use of a hydrophilic composition, that could be utilized on live cells, that would facilitate the use of heat to form a coating on an edible film, and that would not require the use of a solvent to mix compositions to form a medicant-containing layer.
I have discovered an improved film and method for making the same. The film can be used on living cells. Formation of the medicant-containing layer in the film does not require a solvent and minimizes the likelihood of damage from heat and shear. The rate of dissolution or delivery of the medicant by the film can be readily adjusted. The medicant-containing layer, while minimizing the likelihood of heat induced medicant damage, permits heat to be utilized to form a coating on the edible film. Hydrophilic components can be readily incorporated in larger concentrations during production of the medicant-containing layer.