AU779170B2

AU779170B2 - Powder pharmaceutical formulations

Info

Publication number: AU779170B2
Application number: AU19682/01A
Authority: AU
Inventors: Ronald L. Ream; William J. Wokas
Original assignee: WM Wrigley Jr Co
Current assignee: WM Wrigley Jr Co
Priority date: 1999-10-20
Filing date: 2000-10-18
Publication date: 2005-01-13
Anticipated expiration: 2020-10-18
Also published as: JP2003512315A; WO2001028523A1; EP1221941A4; EP1221941A1; CA2382978A1; AU1968201A; CN1374859A

Description

WO 01128523 PCT/US00/41225

SPECIFICATION

TITL

"POWDER PHARMACEUTICAL FORMULATIONS" BACKGROUND OF THE INVENTION The present invention generally relates to the delivery of medicaments and other agents. More specifically, the present invention relates to the delivery of medicaments and agents using powdered formulations.

It is of course known to provide agents to individuals for various purposes. These agents can be used to treat diseases and as such are typically referred to as drugs or medicaments. Likewise, drugs or medicaments can be used for prophylactic purposes.

Still, it is known to provide agents to an individual for a variety of non-medical purposes including enhancing performance or maintaining or initiating alertness. There are a great variety of such agents. These agents run the gamut from stimulants such as caffeine to drugs such as analgesics, tranquilizers, cardiovascular products, insulin, etc. Some such agents are taken on an as needed basis while other agents must be taken at regular intervals by the individual.

Typically, drugs (medicaments) are administered parenterally or enterally. Of course, parenteral administration is the administration of a drug intravenously directly into the blood stream. Enterai refers to the administration of a drug into the gastrointestinal tract. In either case, the goal of the drug administration is to move the drug from the site of administration towards the systemic circulation.

Except when provided intravenously, a drug must traverse several semipermeable cell membranes before reaching general circulation. These membranes act as a biological barrier that inhibits the passage of drug molecules. There are believed to be four processes by which drugs move across a biological barrier: passive diffusion; facilitated diffusion; active transport; and pinocytosis.

Passive diffusion is the transport across the cell membrane wherein the driving force for the movement is the concentration gradient of the solute. In orally administered drugs, this absorption occurs in the small intestines. Facilitated diffusion is believed to be based on a carrier component that combines reversibly with the substrate molecule at the cell membrane exterior. The carrier substrate complex diffuses rapidly across the WO 01/28523 PCTUSOD/41 225 membrane with release of the substrate at the interior surface. Active transport requires an energy expenditure by the cell and appears to be limited to agents with structural similarities to normal body constituents. These agents are usually absorbed from specific sites in the small intestines. Pinocytosis refers to the engulfing of particulars or fluid by a cell. It is believed to play a minor role in drug transport. Merck Manual, 16th Edition, pp. 2598-2599.

In determining the efficacy of a drug and the effectiveness of the use of a drug to treat a disease, drug absorption is a critical concern. Drug absorption refers to the process of drug movement from the site of administration toward the systemic circulation.

Oral administration of drugs is by far the most common method. When administered orally, drug absorption usually occurs due to the transport of cells across the membranes of the epithelial cells within the gastrointestinal tract. Absorption after oral administration is confounded by numerous factors. These factors include differences down the alimentary canniel in: the luminal pH; surface area per luminal volume; perfusion of tissue, bile, and mucus flow; and the epithelial membranes. See Merck Manual at page 2599.

A fuirther issue effecting the absorption of orally administered drugs is the form of the drug. Most orally administered drugs are in the form of tablets or capsules. This is primarily for convenience, economy, stability, and patient acceptance. Accordingly, these capsules or tablets must be disintegrated or dissolved before absorption can occur.

There are a variety of factors capable of varying or retarding disintegration of solid dosage forms. Further, there are a variety of factors that effect the dissolution rate and therefore determine the availability of the drug for absorption. See Merck Manual at page 2600.

Parental administration allows for the direct placement of the drug into the blood stream. This usually insures complete delivery of the dose to the general circulation.

However, administration by a route that requires drug transfer through one or more biologic membranes to reach the blood stream precludes a guarantee that all of the drug will eventually be absorbed. Even with parental administr-ation, because capillaries tend to be highly porous, the perfusion (blood flow/gram of tissue) is a major factor in the rate WO 01/28523 PCT/US00/41225 of absorption. Thus, the injection site can markedly influence a drug's absorption rate; the absorption rate of diazepam injected IM into a site with poor blood flow can be much slower than following an oral dose. See Merck Manual at page 2601.

Not only is drug absorption an issue in drug delivery, but, also the bioavailability of the drug is also critical. Bioavailability is defined as the rate at which and the extent to which the active moiety (drug or metabolite) enters the general circulation, thereby gaining access to the site of action. Bioavailability depends upon a number of factors, including how a drug product is designed and manufactured, its physicochemical properties, and factors that relate to the physiology and pathology of the patient. See Merck Manual at page 2602.

When a drug rapidly dissolves from a drug product and readily passes across membranes, absorption from most site administration tends to be complete. This is not always the case for drugs given orally. Before reaching the vena cava, the drug must move down the alimentary cannel and pass through the gut wall and liver, which are common sites of drug metabolism. Thus, the drug may be metabolized before it can be measured in the general circulation. This causes a decrease in drug input that is called the first pass effect. A large number of drugs show low hioabilities owing to an extensive first pass metabolism. The two other most frequent causes of low bioavailability are insufficient time in the GI tract and the presence of competing reactions. See Merck Manual at page 2602.

Bioavailability considerations are most often encountered for orally administered drugs. Differences in bioavailability can have profound clinical significance.

Although parental administration does provide a method for eliminating a number of the variables that are present with oral administration, parental administration is not a preferable route. Typically, parental administration requires the use of medical personnel and isjust not warranted nor practical for the administration of most agents and drugs, analgesics. Even when required parenteral administration is not preferred due to patient concerns including comfort, infection, etc., as well as the equipment and costs involved. However, despite best efforts certain therapies require parenterally injected drugs. For example, research for decades has focused on an attempt to deliver insulin to an individual through a non-parental means. Despite such efforts today insulin is still only administered intravenously.

A limited number of medicaments have been administered in the form of a powder.

For example, headache powders have been used to provide an enteral method for the delivery of aspirin and other analgesics. Examples of such headache powders are marketed under the brand names BG and Dr. Goodys. These powders are very bitter and typically are not the desired method to enterally ingest an analgesic.

There is therefore a need for an improved method of delivering drugs and agents to an individual.

Summary of the Invention The present invention provides improved methods for delivering a powder medicament or agent to an individual. Improved powder formulations including medicaments and agents are also provided by the present invention. To this end, powders are provided including medicaments or agents. The medicament or agent is present in a powder form mixed with at least a masking agent. It has been found that the masking agent and medicament in powder form have a greater ability to cover up bitter and bad flavors produced by the medicament or agent.

S•According to a first embodiment of the present invention there is provided a method for delivering a medicament in a powder form to an individual comprising the steps of: providing a powder formation that includes a medicament in powder form and S" 20 a sufficient amount of a masking agent to provide acceptable organoleptic properties; and allowing at least a proportion of the powder formulation to dissolve in a mouth of an individual to cause the medicament to be released from the formulation into a S buccal cavity of the individual.

According to a second embodiment of the present invention there is provided a method for reducing the amount of agent necessary to achieve an effect in an individual as compared a typical agent that is swallowed comprising the steps of: •i providing a powder formulation including an agent that is typically swallowed by an individual to achieve a specific effect, the powder formulation including less than the typical amount of agent that is swallowed by the individual to achieve the effect and a sufficient amount of a masking agent to provide acceptable organoleptic properties to the powder formulation; and placing the powder formulation in the buccal cavity of the individual and allows at least a portion of the powder formulation to dissolve in the mouth of the individual and thereby causing the agent to be released into the saliva of the individual.

[R:LIBVV]03413spcci doc.njc 18. NOV. 2004 11:45 SPRUSON FERGUSON NO. 8651 P. 12/19 According to a third embodiment of the present invention there is provided a powder formulation that is designed to dissolve in a mouth of a consumer comprising: a medicament having an offensive taste; and a sufficient amount of a masking agent to provide acceptable organoleptic properties as the medicament dissolves in the mouth and passes through the oral mucosa into the buccal cavity of the consumer.

JIL'd.I8 tiuo a Ltuan embodiment of the present invention there is provided a method of enhancing an individual's performance comprising the steps of: providing a powder formulation including a performance enhancing amount to of caffeine in powder form and a masking agent; and allowing at least a portion of the powder formulation to dissolve in the mouth of the individual not more than ten minutes before the performance.

According to a fifth embodiment of the present invention there is provided a method of delivering a inedicament comprising the steps of: 1s providing a powder formulation including a medicament in powder form and a sufficient amount of a masking agent to mask any offensive tastes that are associated with the medicament; and 0 lw placing the powder formulation in a buccal cavity of an individual and allowing same to dissolve therein.

0 According to a sixth embodiment of the present invention there is provided a 0@ method of increasing the stimulatory effect of a stimulant that has been previously "swallowed by an individual comprising the steps of-, providing a powder formulation that contains the stimulant and a masking agent; and *00 25 placing the powder formulation into the buccal cavity causing the stimulant to be released by the powder formulation into an oral mucosa located in a buccal cavity of the individual, According to a seventh embodiment of the present invention there is provided use of an enhancing amount of caffeine in powder form and a masking agent for the 30 manufacture of a powder formulation to enhance an individual's performance.

According to an eighth embodiment of the present invention there is provided use of a stimulant and masking agent for the manufacture of a powder fbrmulation to increase the stimulatory effect of a stimulant that has been previously swallowed by an individual.

[R:\LIBUU]02986.doc:HIC COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 18. NOV. 2004 11:46 SPRUSON FERGUSON NO. 8651 P. 13/19 According to a ninth embodiment of the present invention there is provided a powder formulation comprising a medicament and a masking agent when used to enhance an individual's performance.

s According to a tenth embodiment of the present invention there is provided a powder formulation comprising a medicament and a masking agent when used to increase the stimuiatory effect of a stimulant that has been previously swallowed by an individual.

The present invention allows a variety of medicaments and agents to be delivered directly into the systemic system of the individual through the oral mucosa contained in the buccal cavity. Such a method can greatly enhance the absorption of the drug into the systemic system as well as the bioavailability of the drug within the system. Absorption of the drug is further enhanced by allowing the consumer to hold the dissolved powder in the mouth for 1 or 2 minutes or longer if comfortable.

To this end, in an embodiment, the present invention provides a powder medicament that is designed to dissolve in the mouth of user. The powder medicament includes a sufficient amount of a masking agent to improve the organoleptic properties of the powdered formula.

In an embodiment, the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antihistamines; decongestants; antacids; antiinflammatories; antibiotics; antivirals; stimulants; psychotherapeutic agents; and cardiovascular agents.

In an embodiment, the masking agent is chosen from the group consisting of: zinc gluconate; ethyl maltol; glycine; acesulfame-K; aspartame, saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; sodium gluconate; glucono delta-lactone; vanillin; normal and high-potency sweeteners; and a variety of appropriate flavors.

In an embodiment, the formation creates a saliva content of medicament of at least to about 66% medicament by weight in the saliva, depending on the medicament.

In another embodiment, the present specification describes a method of enhancing .an individual's performance comprising the steps of: providing a powder formulation S" 30 including a performance enhancing amount of caffeine and a sufficient amount of a masking agent to provide a powder formula with acceptable organoleptic properties; and placing the powder formulation into the buccal cavity not more than ten minutes before the performance.

In an embodiment, the performance to be enhanced is athletic.

In an embodiment, the performance to be enhanced is cognitive.

(R:\LISUUJ02SS6.dac5jU

I

COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 18. NOV. 2004 11:46 SPRUSON FERGUSON NO. 8651 P. 14/19 In an embodiment, the performance to be enhanced is alertness, In an embodiment, the powder formulation is placed in the buccal cavity not more than 5 minutes before the performance.

s Yet further, the present specification describes a method of increasing the stimulatory effect of a stimulant that has been previously ingested by an individual comprising the steps of: providing a powder formulation that contains a powder stimulant and a masking agent; and placing the powder formulation into the buccal cavity causing the stimulant to be released by the powdered formulation. into the oral mucosa of the individual.

In another embodiment, the present specification describes a powder formulation comprising a powder medicament and a sufficient amount of a masking agent to provide a powder formulation having acceptable organoleptic properties.

In a fiurther embodiment of the present invention, a method of delivering a medicament is described. The method comprising the steps of: providing a powder formulation including a powder medicament and a masking agent; and placing the powder formulation in a buccal cavity of an individual and allowing same to dissolve.

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

*5 S S S S [R\LIBUU]0288.doC;1JO 0 COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 WO 01/28523 PCT/US00/41225 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.

Further, an advantage of the present invention is to provide a method of administering a medicament or agent to an individual at a level that is lower than is typically administered orally while still achieving the same effect.

Furthermore, an advantage of the present invention is to provide a method for administering drugs or agents to an individual that heretofore were administered parentally.

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

Another advantage of the present invention is to provide a method for enhancing the performance of an individual through the administration of an agent.

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

Still, an advantage of the present invention is to provide a method for creating a triggering effect that creates a synergistic effect with an agent that is present in the systemic circulation of the individual.

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

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS The present invention provides improved methods for delivering medicaments and other agents to an individual as well as improved formulations including such medicaments and agents. Pursuant to the present invention, a medicament or agent is contained in a powder formulation that includes a masking agent. As used herein, the term "masking agent" includes compounds and agents that alter or disguise the taste of a product that is ingested or placed in the mouth. As such, the term masking agent includes sweeteners and flavors.

WO 01/28523 PCT/US00/41225 It has been found that by adding a masking agent to the powder formulation, that a much more palatable formulation, including a powder medicament, can be provided.

In this regard, even though the medicament in its powder form may be bitter or have an offensive taste, the powder matrix of the present invention, including the masking agent, will afford a product having acceptable organoleptic properties. It has been surprisingly found that by solubilizing a powdered matrix of medicament and masking agent, this increases the ability of the masking agent to cover up bitter and bad flavors produced by the medicament or agent. By selecting specific masking agents based on the bad or off taste produced by the medicament, one can provide a palatable powder formulation.

For example, if one is attempting to cover an astringent flavor such as aspirin, one would use masking agents found to be effective against astringency such as fructose and macro sweeteners, e.g. saccharin, aspartame, and acesulfame-k. In the case of a moderately bitter active ingredient, such as caffeine, one would use ingredients such as glycine, ethyl maltol, zinc gluconate, licorice root powder, micro sweeteners, etc. In the case of a very bad tasking active ingredient such as acetaminophen, combinations of these masking agents or larger quantities may have to be used in order to combat the undesirable bitterness.

The masking agents, in an embodiment, are selected from the group consisting of: zinc gluconate; ethyl maltol; glycine; acesulfame-k; aspartame; saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; sodium gluconate; glucono delta-lactone; and vanillin.

In use, the powder formulation is placed in the mouth of the user. Due to the present invention, the powder formulation has acceptable organoleptic properties allowing the consumer to maintain the powder in his mouth for a sufficient time to allow as much as possible of the powder to dissolve. As the powder formulation dissolves, the powder medicament or agent is released into the saliva. The medicament or agent in the saliva can then pass through the oral mucosa in the buccal cavity. 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 mucous, if the powder is allowed to dissolve in the mouth, an increase in the absorption of the drug is achieved as WO 01/28523 PCTIUS00141225 well as an increase in the bioavailability of the drug as compared to typical oral administration. It has been found that the drug or agent is absorbed much quicker when it is allowed to dissolve in the mouth of the consumer than if it was swallowed as in a typical oral administration.

It is believed that less powder medicament or agent can be placed in the powder formulation than is typically orally administered to an individual to achieve an effect and the same bioequivalence can be achieved.

For example, caffeine is commonly used as a stimulant to alleviate the effects of sleep deprivation. It is almost completely metabolized in the liver and therefore classified as a low clearance, flow independent drug. This means its rate of inactivation is unaffected by delivery to the liver and can only be modified by a change in the hepatic enzyme activity.

The pharmacokinetics of caffeine have been well documented and there is no significant difference between oral and intravenous administration. However, data set forth in detail below, suggests that the absorption rate constant (Ka) is significantly increased when caffeine is administered through chewing gum. This means that the caffeine is moving into the systemic circulation at a significantly faster rate. A similar change in the onset of dynamic response has also been noted, alertness and performance.

It is believed that for at least certain agents that placing the agent in a powder formulation that is placed in the mouth can have a triggering effect on the agent that may be in the systemic circulation. For example, it has been found that with respect to caffeine that is ingested orally, that after the ingestion of a certain amount of caffeine, and the elapse of a certain period of time, that further ingestion of caffeine has a negligible effect on the individual. However, it is believed that if caffeine is placed in a powdered formulation with caffeine there has been observed a triggering effect that appears to create a synergistic effect with the caffeine that is in the systemic circulation.

It is believed that this triggering effect will also be. present with other agents, e.g., analgesics.

It is envisioned, that a variety of different powder medicaments and agents can be used in the powder formulation. For example, such agents include, inter alia, WO 01/28523 PCT/US00/41225 stimulants such as caffeine. Generally, such medicaments include, inter alia, analgesics, antibiotics, antivirals, antihistamines, anti-inflammatories, decongestants, antacids, muscle relaxants, psychotherapeutic agents, insulin, and cardiovascular agents. It is envisioned, that depending on the medicament, the resultant powder formulation 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 iimitation: caffeine; aspirin; acetaminophen; ibuprofen; hydroxycitric acid; chromium picolinate; phosphatidylserine; nicotine; insulin; Echinacea purpurea; zinc; vitamin C; ginseng; kola nut; kaua kaua; and chamomile.

Preferably, the agents or medicaments are contained in the powder formulation at levels of approximately 50 micrograms to 1000 milligrams. The specific levels will depend on the active ingredient. For example, if chromium picolinate is the active ingredient in an embodiment, it would be present at a level of approximately 20 to about 50 micrograms per dosage; aspirin would be preset at a level of approximately 50 to about 650 milligrams per dosage; caffeine would be preset at a level of approximately to about 600 milligrams per dosage; and acetaminophen would be preset at a level of approximately 87 to about 1000 milligrams per dosage.

The level of medicament or agent in the powdered formulation is selected so as to create, when the powder formulation is placed in the mouth, a sufficiently high concentration of the medicament or agent in the saliva.

For example, when the agent is a stimulant such as caffeine, the level of the stimulant in the powder formulation should be such that it creates a saliva content of stimulant of approximately 1% to about 66% after the formulation is placed in the mouth.

At this level, a sufficient amount of stimulant will be delivered to the user to create the effects set forth in the application. If a medicament is used such as a medicinal analgesics), sufficient medicinal should be present in the powder formulation to create a salvia content of approximately 1% to about 66%. For botanicals chamomile, kava, kola, nut, ginseng, and Echinacea), the agent should be present in a sufficient amount to create a saliva content of approximately 1% to about 66%. For a metabolizer, for example, chromium picolineate and hydroxi-chitic acid, the agents should be present WO 01/28523 PC1I7US00/41225 in an amount to create a saliva content of approximately 1% to about 66%. If the agent is a vitamin or mineral phosphatidy serine, vitamin C, and zinc), the agent should be present in the amount to create a saliva content of the vitamin or mineral of approximately 2%to about Pursuant to the present invention, depending on the agent or medicament, the dosing regiment will change. For example, if the medicament is an analgesic, the powdered formulation would be taken on an as needed basis. Of course, similar to the oral administration of an analgesic, there would be restrictions on the doses taken, for example, not more often than one powdered formulation every four hours and not more often than four to five times a day.

If the agent is a stimulant, such as caffeine, to be used to enhance performance than the powdered formulation would be ingested, in a preferred embodiment ten minutes or less before the performance.

Sufficient masking agent will be used to improve and provide acceptable organoleptic properties to the powder product. As used herein to provide "acceptable organoleptic properties" means that the powder formulation will have a sufficiently pleasant, or at least non-offensive taste, to allow the consumer to allow at least a majority of the powder formulation to dissolve in his mouth. The amount of masking agent will thereby vary depending on medicament or agent. Of course, more than one masking agent can be used, zinc gluconate and a sweetener or flavor.

Generally, it is believed that the masking agent will comprise approximately to about 99+% by weight of the powder formulation. For example, if the agent is caffeine, approximately 10 to about 50 milligrams of masking agent should be present per milligram of caffeine; for aspirin, approximately 4 to about 32 milligrams of masking agent should be present per milligram of aspirin; and for acetaminophen, approximately 4 to about 32 milligrams of masking agent should be present per milligram of acetaminophen. Of course, more than one masking agent can be used.

The medicament or agent can be contained in a variety of different powder formulation compositions. For example, the formulation can be low or high moisture, sugar or sugarless, and/or low calorie.

The formulation can include a water soluble bulk portion and one or more WO 01/28523 PCT/US00/41225 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.

Bulk sweeteners, which also can function as the masking agent, include both sugar and sugarless components. Bulk sweeteners, if present, will typically constitute about 50% to about 98% by weight of the formulation. Sugar sweeteners generally include saccharide-containing components commonly known in the confectionary 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 the formulation. Additionally, the softener may also provide additional sweetness such as with aqueous sugar or alditol solutions. As noted above, depending on the powder agent or medicament, sweeteners can comprise a part of, or the entire masking agent.

If a low calorie formulation 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. If present, the flavor 12 can be used in amounts of about 0.5 to about 10 weight percent of the formulation. As noted above, depending on the medicament or agent, flavor can comprise a part of, or the entire masking agent. 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 flavouring agents and components may also be used. Natural and artificial flavoring agents may be combined in any sensorially acceptable fashion.

There are a variety of methods for constructing powder formulations. Generally, the formulations would be constructed by blending a medicament in powder form with a powder masking agent and other components as desired. The blend powder formulation would thus be placed in a package.

Examples By way of example, and not limitation, examples of some powdered formulations including a medicament or agent are as follows: Example 1 Caffeine Powder Formula .Dextrose 95.50% 93.75% 90.75% Flow Agent 1.00% 1.00% 1.00% Zinc Gluconate 0.15% 0.15% 0.15% Caffeine 2.00% 2.00% 5.00% Flavors 1.35% 1.35% 1.35% Macro Sweetener 0.00% 1.75% 1.75% 100.00% 100.00% 100.00% Example 2 Acetaminophen Powder Formula Dextrose 90.50% 88.50% 78.80% Flow Agent 1.00% 1.00% 1.00% Zinc Gluconate 0.15% 0.15% 0.15% Acetaminophen 7.00% 7.00% 16.70% Flavors 1.35% 1.35% 1.35% Macro Sweetener 0.00% 2.00% 2.00% 100.00% 100.00% 100.00% It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such [RALIBVV]03413speci doc.njc 12a changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. It is therefore intended that such changes and modifications be covered by the appended claims.

oo o:o [R.\LIBVV]03413speci.doc njc

Claims

18. NOV. 2004 11:46 SPRUSON FERGUSON NO.8651 P. 15/19 13 The claims defining the invention are as follows: 1. A method for delivering a medicament in a powder form to an individual comprising the steps of: s providing a powder formulation that includes a medicament in powder form and a sufficient amount of a masking agent to provide acceptable organoleptic properties; and allowing at least a portion of the powder formulation to dissolve in a mouth of an individual to cause the medicament to be released from the formulation into a buccal to cavity of the individual. 2. The method of claim 1, wherein the powder formulation includes a sweetener. 3. The method of claim 1 or 2, wherein the powder formulation creates a temporary saliva content of medicament of approximately 5 ppm to about 66% by weight. 4. The method of any one of claims I to 3, wherein the medicament in a powder form is chosen from the group consisting of: analgesics; muscle relaxants; antibiotics; antivirals; stimulants; antihistamines; decongestants; anti-inflammatories; antacids; psychotherapeutic agents; insulin; vitamins; minerals; and cardiovascular agents. 5. The method of any one of claims 1 to 4, wherein the agent is chosen from the group consisting of: zinc gluconate, ethyl maltol, glycine, acesulfame-k, aspartame; 0 saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; sodium gluconate; gluono delta-lactone; vanillin; and cthyl maltol. 6. The method of any one of claims I to 5, wherein the masking agent comprises approximately 50% to about 99% by weight of the formulation. 7. A method for reducing the amount of agent necessary to achieve an effect in an individual as compared a typical agent that is swallowed comprising the steps of: S..providing a powder formulation including an agent that is typically swallowed by an individual to achieve a specific effect, the powder formulation including less than the typical amount of agent that is swallowed by the individual to achieve the effect and a sufficient amount of a masking agent to provide acceptable organoleptic properties to the s0 powdcr formulation; and placing the powder formulation in the buccal cavity of the individual and allows at least a portion of the powder formulation to dissolve in the mouth of the individual and thereby causing the agent to be released into the saliva of the individual. 8. The method of claim 7, wherein the agent is a medicament. [R:\LIDUU02886,doc;I 1O COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 18. NOV. 2004 11:47 SPRUSON FERGUSON NO.8651 P. 16/19 14 9. The method of claim 8, wherein the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antibiotics; antivirals; stimulants; antihistamines; decongestants; anti-inflanmatories; antacids; psychotherapeutic agents; and cardiovascular agents. s 10. The method of claim 7, 8 and 9, wherein the masking agent comprises approximately 50 to about 99% by weight of the powder formulation. II. The method of any one of claims 7 to 10, wherein the powder formulation creates a saliva content of approximately 5 ppm to about 66% by weight agent. 12. A powder formulation that is designed to dissolve in a mouth of a consumer i0 comprising: a medicament having an offensive taste; and a sufficient amount of a masking agent to provide acceptable organoleptic properties as the medicament dissolves in the mouth and passes through the oral mucosa into the buccal cavity of the consumer. 13. The powder formulation of claim 12, wherein the masking agent is chosen from the group consisting of: zinc gluconate, ethyl maltol, glycine, acesulfame-k, aspartame; saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; sodium gluconate; glucono delta-lactone; and vanillin. el" The powder formulation of claim 12 or 13, including a sweetener. 15. The powder formulation of any one of claims 12 to 14, wherein the agent is a stimulant. 16. The powder formulation of any one of claims 12 to 15, wherein approximately 50% to about 99+0o by weight of the formulation is the masking agent. 17. The powder formulation of any one of claims 12 to 16, wherein the medicament is aspirin and the masking agent is a fructose or macro sweetener. 18. The powder formulation of any one of claims 12 to 17, wherein the medicament is acetaminophen and the masking agent is zinc gluconate.

19. A method of enhancing an individual's performance comprising the steps of. providing a powder formulation including a performance enhancing amount of caffeine in powder form a masking agent; and allowing at least a portion of the powder formulation to dissolve in the mouth of the individual not more than ten minutes before the performance. The method of claim 19, wherein the performance to be enhanced is athletic.

21. The method of claim 19, wherein the performance to be enhanced is cognitive. (RALIBUU]02556.doc:HJG 0 COMS ID No: SBM1-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 18, NOV. 2004 11:47 SPRUSON FERGUSON NO.8651 P, 17/19

22. The method of claim 19, wherein the performance to be enhanced is alertness.

23. The method of any one of claims 19 to 22, wherein the formulation is allowed to dissolve five minutes or less before the performance.

24. A method of delivering a medicament comprising the steps of: s providing a powder formulation including a medicament in powder form and a sufficient amount of a masking agent to mask any offensive tastes that are associated with the medicament; and placing the powder formulation in a buccal cavity of an individual and allowing same to dissolve therein. 1o 25. The method of claim 24, wherein the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antibiotics; antivirals; antihistanines; decongestants; anti-inflammatories; antacids; psychotherapeutic agents; and cardiovascular agents.

26. A method of increasing the stimulatory effect of a stimulant that has been previously swallowed by an individual comprising the steps of: providing a powder formulation that contains the stimulant and a masking agent; and placing the powder formulation into the buccal cavity causing the stimulant to be released by the powder formulation into an oral mucosa located in a buccal cavity of o *20 the individual.

27. The method of claim 26, wherein the stimulant is caffeine.

28. The method of claim 26 or 27, wherein the powder formulation creates a saliva content of medicament of approximately 5 ppm to about 66% by weight.

29. The method of any one of claims 26 to 28, wherein the masking agent is chosen from the group consisting of glycine, ethyl maltol, zinc gluconate, and licorice root powder. A method for delivering a medicament in a powder form to an individual comprising the steps of: providing a powder formulation substantially as herein described with reference to Example 1 or 2.

31. A method for reducing the amount of agent necessary to achieve an effect in an individual as compared a typical agent that is swallowed comprising the steps of: providing a powder formulation substantially as herein described with refcrence to Example 1 or 2. [R:\LIBUU]02886.doc:HIJ COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18 18. NOV. 2004 11:47 SPRUSON FERGUSON NO. 8651 18/19 16

32. A powder formulation that is designed to dissolve in a mouth of a consumer substantially as herein described with reference to Example 1 or 2.

33. A method of enhancing an individual's performance comprising the steps of: providing a powder formulation including a performance enhancing amount of caffeine in powder form and a masking agent; and allowing at least a portion of the powder formation to dissolve in the mouth of the individual not more than ten minutes before the performance, which formulation is substantially as herein described with re-fe-rsnce.#- M pv~le 1 orV2.

34. Use of an enhancing amount of caffeine in powder form and a masking agent io for the manufacture of a powder formulation to enhance an individual's performance. Use of an enhancing amount of caffeine in powder form and a masking agent as claimed in claim 32 for the manufacture of a powder formulation to enhance an individual's performance.

36. A method of delivering a medicament comprising the steps of: is providing a powder formulation substantially as herein described with reference to Example 1 or 2.

37. A method of increasing the stimulatory effect of a stimulant that has a been previously swallowed by an individual comprising the steps of: providing a powder formulation that contains the stimulant and a masking 0O."o 20 agent; and placing the powder formulation into the buccal cavity causing the stimulant to be released by the powder formulation into an oral mucosa located in a buccal cavity of 9e 6 0 0 0the individual, which formulation is substantially as herein described with reference to Example 1 or 2. 25 38. Use of a stimulant and masking agent for the manufacture of a powder 99 4@formulation to increase the stimulatory effect of a stimulant that has been previously swallowed by an individual.

39. Use of a stimulant and masking agent for the manufacture of a powder formnulation to increase the stimulatory effect of a stimulant that has been previously swallowed by an individual, which stimulant and masking agent is substantially as herein described with reference to Example 1 or 2. A powder formulation comprising a medicament and a masking agent when used to enhance an individual's performance. (R:\UJ02880.doc:HJ COMS ID No: SBMI-10031 24 Received by IP Australia: Time 11:53 Date 2004-11-18 18. NOV. 2004 11:48 SPRUSON FERGUSON N0. 8651 P. 19/19

41. A powder formulation comprising a medicament and a masking agent when used to enhance an individual's performance, which formulation is substantially as herein described with reference to Example I or 2. 42, A powder formulation comprising a medicament and a masking agent when used to increase the stimulatory effect of a stimulant that has been previously swallowed by an individual.

43. A powder formulation comprising a medicament and a masking agent when used to increase the stimulatory effect of a stimulant that has been previously swallowed by an individual, which formulation is substantially as herein described with reference to Example 1 or 2. Dated 17 November, 2004 Wm. Wrigley Jr. Company Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON 0 *0 .8*0 6 O.00 *5 S C C a 0 toO0: t a*O0C C C C 0 *800 0 0 0* I ee C **e CO C* C CS 050* 0 [R:\LIBUU]02886,doc:IiJO I COMS ID No: SBMI-01003124 Received by IP Australia: Time 11:53 Date 2004-11-18