Title:  Chewable product including active ingredient

United States Patent:  6,613,346

Issued:  September 2, 2003

Inventors:  Seielstad; Donald (Frankfort, IL); Tyrpin; Henry (Palos Park, IL); Broderick; Kevin (Berwyn, IL); Maxwell; James (Chicago, IL); Record; David (River Forest, IL)

Assignee:  Wm. Wrigley, Jr. Company (Chicago, IL)

Appl. No.:  681935

Filed:  June 28, 2001

Abstract

Products and methods of delivering medicaments are provided. The product includes a chewing gum center including a compressible powder that is compressed around the center. The powder includes a medicament that may or may not be encapsulated.

SUMMARY OF THE INVENTION

The present invention provides improved products and methods for delivering a medicament or agent to an individual. Improved formulations including medicaments or agents are also provided by the present invention.

To this end, the present invention provides a chewing gum product including a medicament comprising a chewing gum center and a compressible composition including a medicament, that may be encapsulated, that is compressed around the chewing gum center.

In an embodiment, the product has a disk shape.

In an embodiment, the product has a pellet shape.

In an embodiment, the product has a spherical shape.

In an embodiment, the product has a cube shape.

In an embodiment, the encapsulated medicament is encapsulated with a composition selected from the group consisting of: natural polymers; synthetic polymers; modified cellulosics; and protein.

In an embodiment, the chewing gum center has the same shape as the product.

In an embodiment, the medicament is selected from the group consisting of: analgesics; muscle relaxants; antacids; antihistamines; decongestants; anti-inflammatories; antibiotics; anti-virals; psycotherapeutic agents; hormones; cardiovascular agents; vitamins; minerals; and nutriceuticals.

In an embodiment, the compressible composition includes a masking agent.

In another embodiment of the present invention, a composition including a medicament is provided comprising a chewing gum center and a compressible formulation including a medicament that surrounds the entire chewing gum center.

In an embodiment, the medicament is encapsulated.

In an embodiment, the medicament is encapsulated with a composition selected from the group consisting of: natural polymers; synthetic polymers; modified cellulosics; and protein.

In an embodiment, the medicament is selected from the group consisting of: analgesics; muscle relaxants; antacids; antihistamines; decongestants; anti-inflammatories; antibiotics; anti-virals; psycotherapeutic agents; hormones; cardiovascular agents; vitamins; minerals; and nutriceuticals.

In a further embodiment of the present invention, an acetominophen containing product is provided comprising a chewing gum center and a compressible composition including encapsulated acetaminophen that is compressed around the chewing gum center.

In yet another embodiment of the present invention a method of delivering a medicament is provided comprising the steps of: providing a chewing gum center; compressing around the chewing gum center a composition including a medicament; and causing an individual in need of the medicament to chew the product.

In an embodiment, the medicament is encapsulated.

In an embodiment, the medicament is selected from the group consisting of: analgesics; muscle relaxants; antacids; antihistamines; decongestants; anti-inflammatories; antibiotics; anti-virals; psycotherapeutic agents; hormones; cardiovascular agents; vitamins; minerals; and nutriceuticals.

Still further, in an embodiment, the present invention provides a method for providing a medicament comprising the steps of: providing a chewing gum center; and compressing around the chewing gum center a composition including a medicament.

Additionally, the present invention provides a method of producing a medicament containing product comprising the steps of: producing a chewing gum center; and surrounding the chewing gum center with a powder that includes a medicament.

Accordingly, an advantage of the present invention is to provide new methods for delivering medicaments to an individual.

Furthermore, an advantage of the present invention is to provide improved products containing a medicament.

Still further, an advantage of the present invention is to provide a method of delivering medicaments to an individual that provides for increase absorption and bioavailability as compared to medicaments that are designed to be absorbed in the GI tract.

Another advantage of the present invention is to provide a novel method of delivering medicaments to an individual that provide relief from pain symptoms.

Further, an advantage of the present invention is to provide chewing gum products containing medicaments that have excellent content uniformity.

Still, an advantage of the present invention is to provide a method of delivering medicaments that does not require the individual to take water.

Moreover, an advantage of the present invention is to provide a method for administering medicaments to an individual that heretofore were administered parentally.

Additionally, an advantage of the present invention is to provide a method for administering medicaments that is more palatable than current methods.

Another advantage of the present invention is to provide an improved method for drug delivery.

An additional advantage of the present invention is that it can provide an acetaminophen containing product that can be chewed and is palatable.

Further, an advantage of the present invention is that a chewing gum product including medicament is provided that can have a variety of shapes.

Additional features and advantages of the present invention will be described in and apparent from the detailed description of the invention and the figures.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides improved methods for delivering medicaments and other agents to an individual as well as improved products including such medicaments or agents.

Pursuant to the present invention, a medicament is contained in a compressible formulation that surrounds a gum center. As the chewing gum is chewed, the medicament is released into the saliva. During continual chewing, the medicament in the saliva is then forced through the oral mucosa in the buccal cavity due to the pressure created by the chewing. The oral mucosa has a thin epithelium and a rich vascularity. Thus, the oral mucosa favors drug absorption. In contrast to a typically orally ingested drug, wherein the solution is in contact too briefly for absorption to be appreciable through the oral mucosa, it is believed that during chewing, the agent and/or medicament remains in the buccal cavity and is forced through the oral mucosa. Also it has been surprisingly found that an increase in the absorption of the drug is achieved as well as an increase in the bioavailability of the drug as compared to typical oral administration. It has been found that the medicament is absorbed much quicker than if it was swallowed as in a typical oral administration. Indeed, the absorption may in certain cases approach that of a parenteral administration, and the bioavailability is much greater than oral administration.

Referring to FIG. 1, an embodiment of the product 10 of the present invention is illustrated. As illustrated, the product 10 includes a gum center 12. The gum center 12 can be any chewing gum formulation known in the art. Pursuant to the present invention, surrounding the gum center 12 is a compressed powder 14. The compressed powder 14 is a compressible formulation that is compressed around the chewing gum center 12, and includes a medicament or other active agent. It should be noted, if desired, the gum center can also include medicaments.

By using a compressible formulation including a medicament, a variety of shapes and products can be provided. In the preferred embodiment illustrated in FIG. 1, a disk shaped product 10 is provided. However, any geometry can be created, including cubes, pellets, ovals, and spheres. Further, if desired, indicia can be stamped onto the compressed powder 14 and thereby the product 10.

It should be noted that the gum center 12 can either be completely encased by the compressed powder 14 or it may be partially exposed. Further, the gum center 12 may either have the same shape as the compressed powder 14 and the product 10 or it can have a different shape. For example, a spherical gum center can be utilized with an oval compressed product.

Pursuant to the present invention, a compressible formulation, powder, is compressed around the chewing gum center in order to form the product. This provides advantages over creating chewing gum products that may be coated with a medicament. In this regard, typically chewing gum coatings are created by a pan coating process. The present invention provides a number of advantages over the pan coating processes. Pan coating processes typically allow for less than 200 mg/piece of the active agent. There can also be processing control and dosing issues with respect to products produced using current pan coating processes. Further, pan coated procedures may create stability and shelf life issues with respect to the resultant product.

By utilizing a compressible powder for creating a tableted product, excellent content uniformity can be provided. For example, in an embodiment, it has been found that a product can be provided that will have +3.1% at 300 mg dosage which is +10.9 mgs.

As noted above, the compressible powder includes a medicament. The medicament can be blended with a powder to create the compressed powder through a variety of methods. The blending may be performed by a standard mixing means, using a Vee Blender, a Ribbon Blender or other mixer. The powder is formulated to provide a compressible matrix, using bulk fillers, sorbitols, sugars, polyols, starches, sugars modified with starches and the like. Preferably, this filler can range from approximately 10 to about 95% by weight composition of the powder and active/medicament blend. Preferably the active/medicament may range from approximately 0.001 to about 60% by weight of the powder and active/medicament blend. Other components that can be present in the powder include flavors, colors, sweeteners and high potency sweeteners. Other excipients can also be used in the powder that are useful in modifying mouthfeel and organoleptic properties of the product. Excipients may also be used to modify dissolution and disintegration properties and binding of the product. Preferably the weight of the powder and active/medicament blend may range from approximately 10 to about 90% weight of the total product.

As noted above, if desired, the medicament can be encapsulated or it can be free. In order to produce the encapsulated medicament, a variety of technologies can be utilized. For example, film coating technologies can be used to provide effective taste masking of a pharmaceutical agent. A number of materials can be utilized to encapsulate the medicament including, natural polymers, synthetic polymers, modified cellulose, waxes, fats, oils, and proteins. In addition, a diverse range of modifiers can be used, including, but not limited to, plasticizers, pore formers, disintegrants, waxes, lipids, fats, fatty acids, polylactides, solubilizers, and absorption enhancers.

Several encapsulating techniques can be used to encapsulate the medicament. These include fluid-bed coating and its variations, low-shear wet granulations, high-shear wet granulations, and spray dry processes. The encapsulations provide for coated solid particles and matrix dispersions. This enhances bioavailability, taste masking, and tailored release profiles. It has been found that high-shear granulations of active powder with modifying agents provide for taste masking, absorption enhancement, dissolution aides, and mouth feel modifiers. The tailored release profile focuses on the immediate release of a pharmaceutical/active, a standard delivery profile of pill forms of medicaments/actives and delayed or sustained release of a pharmaceutical active as given by entreric coating processes.

The compressed powder can include masking agents. In this regard, high-intensity sweeteners and appropriate flavors can be used to mask any off notes that are present due to the medicament or agent. It has been found that with respect to certain medicaments or agents that may have an astringent or bitter taste that by adding a masking agent to the formulation, that a much more palatable formulation, including the medicament, can be provided.

The masking agents, in an embodiment, are selected from the group consisting of sucralose; zinc gluconate; ethyl maltol; glycine; acesulfame-k; aspartame; saccharin; fructose; xylitol; maltitol; cooling agents; isomalt; salt; spray dried licorice root; glycyrrhizin; dextrose; sodium gluconate; sucrose; glucono delta-lactone; ethyl vanillin; and vanillin.

In an embodiment of the invention, sufficient masking agent will be used in the compressed powder to improve and provide acceptable organoleptic properties to the chewing gum product. As used herein to provide "acceptable organoleptic properties" means that the product will have a sufficiently pleasant, or at least non-offensive taste, to allow the consumer to chew the chewing gum for at least two minutes. Whether a masking agent is necessary and/or the amount of masking agent will vary depending on medicament. Of course, if desired, more than one masking agent can be used, e.g., zinc gluconate and a sweetener or flavor. In an embodiment, the masking agent may comprise approximately 10% to about 90% by weight of the powder formulation.

In a preferred embodiment, the compressed powder includes a high-intensity sweetener such as aspartame, sucralose, and acesulfame-k. In an embodiment, the high-intensity sweetener comprises approximately 0.5% to about 5% by weight of the coating.

The core, center of the product is chewing gum. It has been found that this component of the present invention reduces any aftertaste that may be present from the medicament. The gum also speeds delivery of the drug by increasing production of saliva. The increase in saliva assists in swallowing the medicament without drinking water. Further an increased absorption is achieved through oral mucosa by creating fluid pressure.

Standard gum formulas known in the art can be used for the chewing gum core center of the product. The chewing gum will be formulated in size, mass and texture to minimize chew-in activity of medicament into the cud. This can be accomplished by increasing the amount of base and filler in the chewing gum. The amount of gum will be enough to provide a reasonable cud size, e.g., in a range of 0.1 grams to 3 grams.

The compression of the powder and medicament blend around the chewing gum center can be performed by modifying existing tableting equipment presently used in the pharmaceutical industry. For example, a modification can be made to equipment as the Single Layer or Multilayer Rotary Tablet Press, to include placement of a core, prior to final compression. The powder blend will then surround the gum core center and is mechanically compressed to form the final product.

It has also been surprisingly found that by placing a medicament in an powder that is compressed around a gum center less medicament or agent can be placed in the product than is typically orally administered to an individual to achieve an effect and the same bioequivalence can be achieved. In fact, it has been surprisingly found that in certain instances, for at least certain drugs and agents, the administration of the medicament or agent using chewing gum through the buccal cavity can provide an increase effect even as compared to parenteral administration.

It is envisioned, that a variety of different medicaments and agents can be placed in the compressed powder. Generally, such medicaments include, inter alia, analgesics, antibiotics, antivirals, antihistamines, anti-inflammatories, cancer chemotherapies, antimycotics, oral contraceptives, diuretics, antitussives, anesthetics, nutraceuticals, bioengineered pharmaceuticals, oral vaccines, probiotics, decongestants, antacids, muscle relaxants, psychotherapeutic agents, hormones, insulin, vitamins, and minerals and cardiovascular agents. For example, such agents include, inter alia, stimulants such as caffeine. It is envisioned, that depending on the medicament, the resultant chewing gum can be used to treat, inter alia: coughs; colds; motion sickness; allergies; fevers; pain; inflammation; sore throats; cold sores; sinus problems; diarrhea; diabetics; depression; anxiety; and other maladies and symptoms. Specific agents/medicaments include, by way of example and not limitation: caffeine; aspirin; acetaminophen; ibuprofen; hydroxycitric acid; antacids; chromium picolinate; phosphatidylserine; nicotine (for smoking cessation); insulin; Echinacea purpurea; zinc; vitamin C; ginseng; kola nut; kaua kaua; and chamomile.

In an embodiment, the medicaments are contained in the compressed powder coating of the chewing gum formulation at levels of approximately 50 micrograms to 500 milligrams. The specific levels will depend on the active ingredient. The level of medicament or agent in the compressed powder of the chewing gum formulation is selected so as to create, when the product is chewed, a sufficiently high concentration of the medicament or agent in the saliva.

In an embodiment of the present invention, the product includes encapsulated acetaminophen. Preferably the product includes at least 250 mg of acetaminophen and in an embodiment 500 mg. It has been found that the acetaminophen is quickly released from the product into the saliva of the individual chewing the product.

Pursuant to the present invention, depending on the medicament, the dosing regiment will change. For example, if the medicament is an analgesic, the chewing gum would be taken on an as needed basis. Of course, similar to the oral administration of an analgesic, there would be restrictions on the number of pieces of chewing gum, chewed, for example, not more often than one stick every four hours and not more often than four to five times a day.

The powder including medicament can surround a variety of different gum center compositions. Referring now to the chewing gum center, pursuant to the present invention, the gum center may be based on a variety of different chewing gums that are known. For example, the gum center can be low or high moisture, sugar or sugarless, wax containing or wax free, low calorie (via high base or low calorie bulking agents), and/or may contain dental agents.

Chewing gum generally consists of a water insoluble gum base, a water soluble portion, and flavor. The water soluble portion dissipates with a portion of the flavor of the gum over a period of time during chewing. The gum base portion is retained in the mouth throughout the chew.

The insoluble gum base generally comprises elastomers, resins, fats and oils, softeners and inorganic fillers. The gum base may or may not include wax. Typically, gum base comprises approximately 20 to about 40% of the gum product. However, because in the present invention such a high level of coating is used, the gum center is unusually small; otherwise the entire coating chewing gum piece would be too large for consumption. If atypical amount of gum base was used in the small gum center, it would result in an inadequate cud to masticate. Consequently, in the present invention, the base level is higher than normal. The insoluble gum base can constitute approximately 30% to about 90% by weight of the chewing gum, in an embodiment, the gum base comprises at least 50% of the chewing gum.

In an embodiment, the chewing gum base of the present invention contains about 20% to about 60% by weight synthetic elastomer, about 0% to about 30% by weight natural elastomer, about 5% to about 55% by weight elastomer plasticizer, about 4% to about 35% by weight filler, about 5% to about 35% by weight softener, and optional minor amounts (about 1% or less by weight) of miscellaneous ingredients such as colorants, antioxidants, etc.

Synthetic elastomers may include, but are not limited to, polyisobutylene with GPC weight average molecular weight of about 10,000 to about 95,000, isobutylene-isoprene copolymer (butyl elastomer), styrene-butadiene, copolymers having styrene-butadiene ratios of about 1:3 to about 3:1, polyvinyl acetate having GPC weight average molecular weight of about 2,000 to about 90,000, polyisoprene, polyethylene, vinyl acetate--vinyl laurate copolymer having vinyl laurate content of about 5% to about 50% by weight of the copolymer, and combinations thereof.

Preferred ranges for polyisobutylene are 50,000 to 80,000 GPC weight average molecular weight and for styrene-butadiene are 1:1 to 1:3 bound styrene-butadiene, for polyvinyl acetate are 10,000 to 65,000 GBC weight average molecular weight with the higher molecular weight polyvinyl acetates typically used in bubble gum base, and for vinyl acetate-vinyl laurate, vinyl laurate content of 10-45%.

Natural elastomers may include natural rubber such as smoked or liquid latex and guayule as well as natural gums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata, massaranduba chocolate, nispero, rosindinha, chicle, gutta hang kang, and combinations thereof. The preferred synthetic elastomer and natural elastomer concentrations vary depending on whether the chewing gum in which the base is used is adhesive or conventional, bubble gum or regular gum, as discussed below. Preferred natural elastomers include jelutong, chicle, sorva and massaranduba balata.

Elastomer plasticizers may include, but are not limited to, natural rosin esters such as glycerol esters or partially hydrogenated rosin, glycerol esters of polymerized rosin, glycerol esters of partially dimerized rosin, glycerol esters of rosin, pentaerythritol esters of partially hydrogenated rosin, methyl and partially hydrogenated methyl esters of rosin, pentaerythritol esters of rosin; synthetics such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene; and any suitable combinations of the foregoing. The preferred elastomer plasticizers will also vary depending on the specific application, and on the type of elastomer which is used.

Fillers/texturizers may include magnesium and calcium carbonate, ground limestone, silicate types such as magnesium and aluminum silicate, clay, alumina, talc, titanium oxide, mono-, di- and tri-calcium phosphate, cellulose polymers, such as wood, and combinations thereof.

Softeners/emulsifiers may include tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glycerol monostearate, glycerol triacetate, lecithin, mono-, di- and triglycerides, acetylated monoglycerides, fatty acids (e.g. stearic, palmitic, oleic and linoleic acids); and combinations thereof.

Colorants and whiteners may include FD&C-type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof.

The base may or may not include wax. An example of a wax-free gum base is disclosed in U.S. Pat. No. 5,286,500, the disclosure of which is incorporated herein by reference.

In addition to a water insoluble gum base portion, a typical chewing gum composition includes a water soluble bulk portion and one or more flavoring agents. The water soluble portion can include bulk sweeteners, high-intensity sweeteners, flavoring agents, softeners, emulsifiers, colors, acidulants, fillers, antioxidants, and other components that provide desired attributes.

Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum. The softeners, which are also known as plasticizers and plasticizing agents, generally constitute between approximately 0.5% to about 15% by weight of the chewing gum. The softeners may include glycerin, lecithin, and combinations thereof. Aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolysates, corn syrup and combinations thereof, may also be used as softeners and binding agents in chewing gum.

Bulk sweeteners include both sugar and sugarless components. Bulk sweeteners typically constitute about 5% to about 95% by weight of the chewing gum, more typically, about 20% to about 80% by weight, and more commonly, about 30% to about 60% by weight of the gum. Sugar sweeteners generally include saccharide-containing components commonly known in the chewing gum art, including but not limited to, sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, glactose, corn syrup solids, and the like, alone or in combination. Sugarless sweeteners include, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, and the like, alone or in combination.

High-intensity artificial sweeteners can also be used, alone or in combination, with the above. Preferred sweeteners include, but are not limited to, sucralose, aspartame, salts of acesulfame, altitame, saccharin and its salts, cyclamic acid and its salts, glycerrhizinate, dihydrochalcones, thaumatin, monellin, and the like, alone or in combination. In order to provide longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweetener. Such techniques as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, coacervation, and fiber extension may be used to achieve the desired release characteristics.

Combinations of sugar and/or sugarless sweeteners may be used in chewing gum. Additionally, the softener may also provide additional sweetness such as with aqueous sugar or alditol solutions.

If a low calorie gum is desired, a low caloric bulking agent can be used. Examples of low caloric bulking agents include: polydextrose; Raftilose, Raftilin; Fructooligosaccharides (NutraFlora); Palatinose oligosaccharide; Guar Gum Hydrolysate (Sun Fiber); or indigestible dextrin (Fibersol). However, other low calorie bulking agents can be used.

A variety of flavoring agents can also be used, if desired. The flavor can be used in amounts of about 0.1 to about 15 weight percent of the gum, and preferably, about 0.2% to about 5% by weight. Flavoring agents may include essential oils, synthetic flavors or mixtures thereof including, but not limited to, oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, other mint oils, clove oil, oil of wintergreen, anise and the like. Artificial flavoring agents and components may also be used. Natural and artificial flavoring agents may be combined in any sensorially acceptable fashion.

The gum center can be prepared using a variety of different methods and machinery known in the art. For example, the formulation can be mixed using a sigma blade mixer. The center formulation may also be made by continuous processing equipment known in the art. Conventional sheeting and scoring machinery can be used to form and score the centers or the centers can be made on a forming machine that involves a drop frame and nitrogen cooling allowing spheres, ovals, and other shapes to be made.

Claim 1 of 32 Claims

What is claimed is:

1. A chewing gum product including a medicament comprising:

a chewing gum center; and

a compressible composition comprising an encapsulated medicament that is compressed around the chewing gum center.

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