WO2000035295A1 - Controlling release of active agents from a chewing gum coating - Google Patents

Abstract

A method for producing a coated chewing gum with a controlled release of an active agent, as well as the chewing gum so produced, is obtained by physically modifying an active agent's properties by coating and drying. An active agent is coated by encapsulation, partially coated by agglomeration, entrapped by absorption, or treated by multiple steps of encapsulation, agglomeration, and absorption. The coated active agent is then co-dried and particle sized to produce a release-modified active agent. When incorporated into a chewing gum coating, these particles release into the mouth but mask bitter and other off-tastes in the mouth, and are readily ingested.

Description

CONTROLLING RELEASE OF ACTIVE AGENTS FROM A CHEWING GUM COATING

The present invention claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application 60/112,389 filed December 15, 1998. The entire text of the referenced application is incorporated herein by reference without prejudice or disclaimer.

BACKGROUND OF THE INVENTION

The present invention relates to methods for producing chewing gum. More particularly the invention relates to producing chewing gum containing an effective amount of an active ingredient or ingredients, including a stimulant known as caffeine. The caffeine or other active ingredient that is added to the chewing gum has been treated to control its rate of release from chewing gum by adding the treated active agent to a gum coating.

In recent years, efforts have been devoted to controlling release characteristics of various ingredients in chewing gum. Most notably, attempts have been made to delay the release of sweeteners and flavors in various chewing gum formulations to thereby lengthen the satisfactory chewing time of the gum. Delaying the release of sweeteners and flavors can also avoid an undesirable overpowering burst of sweetness or flavor during the initial chewing period. On the other hand, some ingredients have been treated so as to increase their rate of release in chewing gum.

Besides sweeteners, other ingredients may require a controlled release from chewing gum. In certain embodiments, it is contemplated that the active agent that is added to the gum may be a stimulant such as caffeine. However, stimulants are not generally released very readily. An active stimulant such as caffeine may be encapsulated in a water soluble matrix such that, during the chewing period, the caffeine may be released quickly, resulting in a fast release of stimulant as in a beverage. This would allow chewing gum to be a carrier for an active agent such as caffeine and, with these fast release characteristics the gum may be used as an effective stimulant. In some instances serious taste problems may arise because of the bitter nature of many active agents A prolonged or delayed release of an active agent(s) would allow for the use of the active ageπt(s) in gum but the low level of release of such an agent may keep the level of that agent below the taste threshold of the active agent and not give chewing gum a bitter taste quality In addition active agents may also have other unpleasant tastes that may be overcome by reducing the release rate of active agent from a chewing gum

Another aspect of the present invention contemplates the use of encapsulation techniques For example it may be that active agents may also be unstable in a chewing gum environment In such cases various methods of encapsulation may be needed to improve stability of the active agent In other circumstances active agents may not be readily released from the chewing gum matrix and their effect may be considerably reduced In such a situation, a fast release encapsulation may be needed to release active agent(s) from the gum matrix

Other methods contemplated are method of controlling release of active agent(s) from gum These methods would be useful in not releasing the active agent in the oral cavity during gum chewing, but allowing the active agent to be ingested during chewing This will keep the active agent from becoming effective until after it enters the digestive track

Thus there are specific advantages to adding active agent(s) to chewing gum by controlled release mechanisms

The use of caffeine in chewing gum is disclosed in U S Patent No 1 ,298,670 The controlled release of caffeine in chewing gum is disclosed in

PCT Patent Publication No WO 98/23165

Chewing gum containing caffeine as a stimulant and to combat fatigue and migraine headaches is disclosed in French Patent No 2 345 938 and in West Germany Patent No 43 42 568 Also two Japanese Patent Publications Nos JP 1991 -1 12450 and JP

1991 -251533 disclose the use of caffeine in chewing gum to reduce drowsiness In Japanese Patent Publication No JP 1996-019370 caffeine is added to chewing gum as an after meal chewing gum to replace tooth brushing

Caffeine is a well known stimulant from coffee and tea and several patents disclose the use of coffee or tea in gum, such as Japanese Patent Publication No JP 1994-303911 South Korea Patent Publication No 94-

002868 and PCT Patent Publication No WO 95/00038

SUMMARY OF THE INVENTION

The present invention provides a method of producing chewing gum with physically modified active agents such as caffeine to control their release Such active agents are added to a gum coating to deliver the active agents systemically without unpleasant tastes The present invention also relates to the chewing gum so produced Physically modified active agents such as caffeine may be added to sucrose-type gum formulations and sucrose-type coatings The formulation may be a low or high moisture formulation containing low or high amounts of moisture containing syrup Physically modified active agents such as caffeine may also be used in low or non-sugar gum formulations and coatings that use sorbitol, mannitol, other polyols or carbohydrates Non-sugar formulations may include low or high moisture sugar-free chewing gums Active agents such as caffeine and the other active agents described herein may be combined or co-dried with bulk sweeteners typically used in chewing gum before the active agent(s) are physically modified Such bulk sweeteners are sucrose, dextrose, fructose and maltodextπns, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates

The modified release rate noted above may be a fast release or a delayed release The modified release of active agents such as caffeine may be obtained by encapsulation, partial encapsulation or partial coating, entrapment or absorption with high or low water soluble materials or water insoluble materials The procedures for modifying the active agent include spray drying, spray chilling, fluid bed coating coacervation extrusion and 5295

other agglomerating and standard encapsulating techniques The active agents also may be absorbed onto an inert or water-insoluble material Active agents may be modified in a multiple step process comprising any of the processes or a combination of the processes noted Prior to encapsulation, active agents may also be combined with bulk sweeteners including sucrose, dextrose fructose maltodextππ or other bulk sweeteners, as well as sugar alcohols such as sorbitol mannitol xylitol maltito! lactitol hydrogenated isomaltuiose and hydrogenated starch hydrolyzates

Prior to encapsulation active agents such as caffeine may be combined with high-intensity sweeteners including but not limited to thaumatm, aspartame alitame, acesulfame K, saccharin acid and its salts, glycyrrhizin cyclamate and its salts stevioside and dihydrochalcones Co- encapsulation of active agents along with a high-intensity sweetener may reduce the poor taste qualities of active agents and control the sweetener release with active agents This can improve the quality of the gum product and increase consumer acceptability

Preferably, the physically modified active agents such as caffeine are mixed with a panning syrup and then applied as a chewing gum coating The coating is applied by panning techniques that may use sugars for a sugar panned product or may use sorbitol, xylitol, or other polyols to make either a soft or hard shell sugarless panned product By adding physically modified active agents to a gum coating, the active agents will not be available in the mouth for tasting, but carried with the carbohydrate used in the coating and ingested into the digestive system, where the active agents can be absorbed systemically for its effect This technique significantly reduces the overall poor quality taste of active agents as it is masked by the encapsulant in the mouth during chewing and results in a gum product having increased consumer acceptability

BRIEF DESCRIPTION OF THE DRAWING Figure 1 shows the results of a bitterness time-intensity sensory test for two gum samples with a coating containing caffeine with one sample containing encapsulated caffeine and the other containing unencapsulated caffeine.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Caffeine is a natural chemical found in a variety of food products such as coffee, tea. cocoa, chocolate, and various other beverages. Caffeine is known as an effective stimulant to increase energy and reduce drowsiness. Caffeine has a naturally bitter taste. The bitterness, however, actually improves the flavor perception of some beverages such as coffee and carbonated beverages. When caffeine is added to stick chewing gum at a level of about 0.2% to about 5%. caffeine imparts an intense bitterness to the chewing gum that lasts throughout the chewing period. The higher the level used, the stronger the bitterness. At about 0.2%, which is about 5 mg per 2.7 gram stick, the bitterness is below the threshold limit and is not readily discernible. Taste limits in stick chewing gum are generally about 0.4% (10 mg) to about 4%

(100 mg) of caffeine in a stick of gum. The 60-80 mg level of caffeine is about the level of caffeine found in a conventional cup of coffee. The target level of caffeine in stick gum is about 40 mg per stick, with a range of about 25-60 mg, so that a five stick package of gum would contain about 200 mg of caffeine, or the equivalent of caffeine in two strong cups of coffee However at this level caffeine bitterness overwhelms the flavor initially and lasts throughout the chewing period.

For coated pellet gum, piece weight is generally about 1.5 grams per piece. However, one coated piece of gum is about equal to 1/2 piece of stick gum Two pellets are equivalent to a stick of gum, and together weigh about

3 grams The above-noted target level of 40 mg per stick is equivalent to 20 mg per coated piece, or a range of about 12 to 30 mg caffeine per piece This is about 0 8% to about 2% caffeine in a piece of coated gum, or a target level of 1.3% Caffeine is not a highly water soluble substance and. therefore, has a moderately slow release from stick chewing gum Caffeine is 2.1 % soluble in water at room temperature, 15% soluble in water at 80°C and 40% soluble in boiling water. This gives caffeine a moderately slow release as shown below:

Chewinq Time % Caffeine Release

0 min

5 min 56

10 min 73

20 min 88

40 min 97

Generally, highly water soluble ingredients in stick gum are about 80- 90% released after only five minutes of chewing. For caffeine, only about 50% is released, while the other 50% remains in the gum after five minutes of chewing. After 20 minutes almost 90% of caffeine is released. Even if caffeine is dissolved in hot water and mixed in the stick gum, when the gum is cooled or kept at room temperature, caffeine may return to its normal crystalline state and release at the same rate as shown above.

When unmodified caffeine is added to a coating of a coated gum piece, the coating, which is very water soluble and is very easily dissolved in the mouth, will dissipate in the mouth very quickly. This will give a fast release of caffeine into the mouth, giving a very strong bitter taste. This bitter taste from the caffeine will remain in the mouth even after the caffeine has been ingested. However, when an encapsulated caffeine is employed in the gum coating, upon dissipation of the encapsulated caffeine in the mouth the encapsulating agent masks or shields the caffeine from the taste receptors of the mouth, thus reducing the bitterness experienced by the chewer. After being ingested into the digestive tract, the caffeine will be released from its encapsulating agent and will be absorbed and effective as a stimulant. Accordingly, the employment of encapsulated caffeine in a chewing gum coating allows for the delivery of caffeine to a user in a manner which does not result in the user experiencing significant bitterness, and at a minimum results in the user experiencing significantly less bitterness than would be experienced utilizing unencapsulated caffeine in the coating. Furthermore, the use of encapsulated caffeine in a gum coating allows for significantly higher levels of caffeine to be provided in a given piece of coated gum without the chewer experiencing the bitterness associated with the caffeine than would otherwise be achievable in the absence of caffeine encapsulation This would allow for delivery of caffeine levels on the order of that found in a cup of coffee to be provided in only two or possibly even only one, piece of coated gum, without the chewer experiencing the bitterness which would otherwise result in the absence of encapsulating the caffeine Additionally, the encapsulating agent may be selected to provide a time delay of release of the caffeine or two or more encapsulating agents may be utilized having different release rates to provide a selectively controlled time release of the caffeine subsequent to ingestion of the caffeine

Caffeine salt compounds such as caffeine citrate, caffeine sodium benzoate caffeine sodium salicylate, which may be more water soluble and less bitter than caffeine, may also be encapsulated or entrapped for use in a chewing gum coating in accordance with the present invention

Other active agents or medicaments that may have a bitter or unpleasant off-taste may be included in the present invention By the terms "active agent" the present invention refers to a compound that has a desired therapeutic or physiological effect once ingested and/or metabolized The therapeutic effect may be one which decreases the growth of a xenobiotic or other gut flora or fauna alters the activity of an enzyme, provides the physical relief from a malady (e g , diminishes pain acid reflux or other discomfort), has an effect on the brain chemistry of molecules that determine mood and behavior Of course these are just examples of what is intended by therapeutic effect Those of skill in the art will readily recognize that a particular agent has or is associated with a given therapeutic effect

The active agent may be any agent that is traditionally used as a medicament and lends itself to being administered through the oral cavity Such active agents may be vitamins chemotherapeutics antimycotics oral contraceptives nicotine or nicotine replacement agents minerals analgesics antacids muscle relaxants antihistamines decoπgestants anesthetics, antitussives diuretics anti-inflammatoπes antibiotics, aπtivirals, psychotherapeutic agents anti-diabetic agents and cardiovascular agents, nutraceuticals and nutritional supplements

Vitamins and co-enzymes that may be delivered using this invention include but are not limited to water or fat soluble vitamins such as thiamin, πboflavin nicotinic acid, pyπdoxine pantothenic acid, biotin, flavin, choline, inositol and paraminobenzoic acid, carnitine, vitamin C vitamin D and its analogs, vitamin A and the carotenoids, retinoic acid vitamin E and vitamin K Examples of chemotherapeutics agents include but are not limited to cisplatin (CDDP), procarbazme, mechlorethamine, cyclophosphamide, camptothecin ifosfamide, melphalan chlorambucil, bisuifan nitrosurea, dactinomycin daunorubiciπ doxorubicin bleomycin, plicomycin, mitomycin, etoposide (VP16), tamoxifen, taxol, transplatinum, 5-fluorouracιl, vincnstin, vinblastin and methotrexate or any analog or derivative variant thereof Antimicrobial agents that may be used include but are not limited to naficillin, oxacillin, vancomycin, clindamycin, erythromycin, tπmethopπm- sulphamethoxazole, πfampin, ciprofloxacin, broad spectrum penicillin, amoxicillin, gentamicin, ceftπazoxone, cefotaxime, chloramphenicol, clavunate, sulbactam, probenecid, doxycycline, spectinomycin, cefixime, penicillin G minocycline β-lactamase inhibitors, mezlocillin piperacilhn, aztreonam norfloxacin tπmethopπm ceftazidime dapsone

Antifungal agents that may be delivered include but are not limited to ketoconazole flucoπazole, nystatm itraconazole, clomitrazole, and amphotencin B Antiviral agents that may be used include but are not limited to acyclovir tπfluπdine idoxorudine foscamet, ganciciovir zidovudine, dideoxycytosine dideoxyinosine, stavudine famciclovir didanosine, zalcitabine, πfimantadine and cytokines

Antacids include cimetidine ranitidine nizatidine famotidine omeprazole bismuth antacids metronidazole antacids tetracylcine antacids clarthromycin antacids hydroxides of aluminum magnesium sodium bicarbonates calcium bicarbonate and other carbonates silicates and phosphates Antihistamines are represented by but are not limited to cimetidine ranitidine diphenydramine prylamine promethazine chlorpheniramine chlorcyc zine terfenadine carbinoxamine maleate clemastine fumarate diphenhydramine hydrochloride dimenhydπnate pπlamine maleate tπpelennamine hydrochloride tπpelennamine citrate chlorpheniramine maleate brompheniramine maleate hydroxyzine pamoate hydroxyzine hydrochloride cyclizine lactate cyc ziπe hydrochloride, meclizine hydrochloride acnvastine cetiπzine hydrochloride astemizole levocabastine hydrochloride and loratadine Decongestants and antitussives include agents such as dextromethorphan levopropoxyphene napsylate noscapine carbetapentane caramiphen chlophedianol pseudoephednne hydrochloride diphenhydramine, glaucine pholcodine and benzonatate

Anesthetics include etomidate ketamine propofol and benodiazapines (e g , chlordiazepoxide diazepame clorezepate, halazepam flurazepam quazepam estazolam, tπazoiam alprozolm, midazolam temazepam oxazepam lorazepam), benzocame dyclonine, bupivacaine, etidocaine, lidocaine mepivacaine, promoxine pπlocaine procaine proparcaine, ropivacaine tetracaine Other useful agents may include amobartital aprobarbital butabarbital butalbital mephobarbital methohexital pentobarbital phenobarbital secobarbital thiopental paral chloral hydrate ethchlorvynol clutethimide methpryloπ ethinamate and meprobamate

Analgesics include opioids such as morphine mepidine dentanyl sufentranil alfentanil aspirin acetaminophen ibuprofen indomethacine naproxen atπn isocome midπn axotal fiπnal phrenilin ergot and ergot derivatives (wigraine cafergot ergostat ergomar dihydroergotamine) imitrex

Diuretics include but are not limited to acetazolamide dichlorphenamide methazolamide furosemide bumetanide ethacrynic acid torseimde azosemide muzolimine piretanide tπpamide bendroflumethiazide benzthiazide chlorothiazide hydrochlorothiazide hydroflumethiazide methyclothiaz'de polythiazide tnchlormethiazide indapamide metolazone quinethazone amiloπde tπamterene spnonolactone canrenone and potassium canrenoate

Anti-inflammatoπes include but are not limited to salicylic acid derivatives (e g aspirin) paraminophenol derivative (e g acetaminophen) indole and indene acetic acids (mdomethacin, sulindac and etodalac) heteroaryl acetic acids (tolmetin diclofenac and ketorolac) aryl propionic acid derivatives (ibuprofen naproxen ketoprofen fenopren oxaprozine), anthranilic acids (mefenamic acid, meclofenamic acid) enolic acids (piroxicam tenoxicam, phenylbutazone and oxyphenthatrazone) Psychotherapeutic agents include thorazine, serentil mellaπl, millazine, tindal permitil prolixin tnlafon stelazine suprazine taractan navan clozaπl, haldol halperon loxitane moban orap, πsperdal alprazolam chlordiaepoxide clonezepam clorezepate diazepam, halazepam lorazepam, oxazepam, prazepam, buspirone elvavil, anafranil, adapin, sinequan, tofranil, surmontil, asendin, norpramin, pertofrane, ludiomil, pamelor vivactil, prozac, luvox, paxil, zoloft, effexor, wellbutnn, serzone, desyrel, nardil, parnate, eldepryl

Cardiovascular agents include but are not limited to nitroglycenn, isosorbide dinitrate, sodium nitropnsside, captopnl, enalapπl enalapnlat, quinapnl lisinopnl ramipnl, losartan amnnone, linnone, vesnennone, hydralazine nicorandil prozasin doxazosm bunazosin tamulosin yohimbine propanolol metoprolol nadolol atenolol timolol esmolol pindolol, acebutolol labetalol phentolamine carvedilol bucindolol verapamil nifedipine amlodipine and dobutamine It is envisioned that depending on the active agent or medicament, the resultant chewing gum can be used to treat inter alia coughs colds motion sickness allergies fevers, pain inflammation sore throats cold sores, migraines sinus problems diarrhea diabetes gastritis depression anxiety, hypertension angina and other maladies and symptoms Also these gums may be useful in ameliorating cravings in substance abuse withdrawal

Specific active agents or medicaments include by way of example and limitation caffeine aspirin acetaminophen ibuprofen cimetidine ranitidine, famotidine dramamine, omeprazole, dyclonine chlorpheniramine maleate, pseudoephedπne hydrochloride dextromethorphan benzocaine. naproxen, and nicotine

Compositions that may be formulated into a suitable chewing gum formulation are described in for examples U S Patent No 5,858,423, U S

Patent No 5,858 413 U S Patent No 5,858,412 and U S Patent No 5,858.383 Additionally, Goodman and Gilman's "The Pharmaceutical Basis of Therapeutics" (Eds Hardman et al , Publ. McGraw Hill, NY) provides comprehensive guidance of useful drugs and their mechanisms of action Medicated chewing gums have been particularly effective in the delivery of agents such as nicotine as described in for example, U S. Patent No 5,866.179 and U S Patent No 5,889,028 U S Patent No 5,846,557 describes general chewing gum compositions containing cough suppressing agents These patents are incorporated herein by reference as providing a teaching of the incorporation of medicinal agents into oral chewable formulations It should be understood that the present chewing gum formulatιon(s) are not limited to the agents listed herein above, indeed any medicinal or other active agent that lends itself to ingestion may be formulated into the chewing gum formulations of the present invention Nutraceuticals and nutritional supplements may also be added to chewing gums as active agents Among these are herbs and botanicals that include, but are not limited to capsicum, chamomile, cat's claw, echinacea, garlic ginger, ginko, various ginseng, green tea. golden seal, kava kava, nettle, passion flower saw palmetto, St John's wort, and valerian Also included are mineral supplements such as calcium copper iodine iron, magnesium manganese molybdenum, phosphorous and selenium Other nutraceuticals that also can be added to chewing gum as active agents are fructo-oligosacchaπdes glucosamine, grapeseed extract guarana, mulin, phytosterols, phytochemicals isoflavones lecithin lycopene oligofructose, polyphenol and psyl um as well as weight loss agents such as chromium picolinate and phenylpropionylamine Preferably, the active agents or medicaments are contained in the chewing gum formulation at levels of approximately 50 micrograms to 500 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 50 micrograms per serving (3.0 grams/two pieces of gum), aspirin would be preset at a level up to 325 milligrams per 3.0/gram serving (two pieces) To obtain the higher levels, additional coatings in the gum will be needed This will increase piece size for a two piece serving size. If the agent is a stimulant, such as caffeine, to be used to enhance performance then the chewing gum would be chewed, in a preferred embodiment ten minutes or less before the performance. It has been surprisingly found that with an extra five minutes of chewing a caffeine- containing chewing gum a high level of alertness is achieved. The medicament or active agent can be contained in a variety of different chewing gum compositions. Referring now to the chewing gum, pursuant to the present invention, the chewing gum including the medicament or active agent may be based on a variety of different chewing gums that are known. For example, the chewing gums 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.

Pursuant to the present invention, depending on the active agent or 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 two pieces every four hours and not more often than four to five times a day

Physical modifications of the active agent such as caffeine by encapsulation with a highly water soluble substrate will increase its release in stick chewing gum as well as from the gum coating by increasing the solubility or dissolution rate of caffeine. However preferably the active agent such as caffeine may also be encapsulated or entrapped to give a delayed release from stick chewing gum and from a gum coating. Any standard technique which gives partial or full encapsulation of the active agent can be used. These techniques include, but are not limited to, spray drying, spray chilling, fluid-bed coating and coacervation. These encapsulation techniques may be used individually in a single step process or in any combination in a multiple step process.

Active agents such as caffeine may be encapsulated with sweeteners, more specifically high-intensity sweeteners such as thaumatin, dihydrochalcones, acesulfame K, aspartame, sucralose, alitame, saccharin and cyclamates. These can also have the effect of reducing unpleasant tastes such as bitterness. Additional bitterness inhibitors or taste maskers can also be combined with active agents and sweeteners to give a reduced unpleasant taste such as bitterness with delayed release active agent(s). The encapsulation techniques described herein are standard coating techniques and generally give varying degrees of coating from partial to full coating, depending on the coating composition used in the process. Generally, compositions that have high organic solubility, good film-forming properties and low water solubility give better delayed release of active agents such as caffeine, while compositions that have high water solubility give better fast release. Such low water-solubility compositions include acrylic polymers and copolymers, carboxyvinyl polymer, polyamides, polystyrene, polyvinyl acetate, polyvinyl acetate phthalate, polyvinylpyrrolidone and waxes. Although all of these materials are possible for encapsulation of active agents such as caffeine, only food-grade materials should be considered. Two standard food-grade coating materials that are good film formers but not water soluble are shellac and Zein. Others which are more water soluble, but good film formers, are materials like agar, alginates, a wide range of cellulose derivatives like ethyl cellulose, methyl cellulose, sodium hydroxymethyl cellulose, and hydroxypropylmethyl cellulose, dextrin, gelatin, and modified starches. These ingredients, which are generally approved for food use. may give a fast release when used as an encapsulant. Other encapsulants like acacia or maltodextπn can also encapsulate active agent(s) and give a fast release rate in gum

The amount of coating or encapsulating material on the active agent also may control the length of time for its release from chewing gum Generally, the higher the level of coating and the lower the amount of active agent the slower the release during mastication with low water soluble compositions The release rate is generally not instantaneous, but gradual over an extended period of time for stick gum When used in a coating, delayed release allows the active agent to be masked in the mouth before being ingested thus reducing bitterness or other unpleasant tastes To obtain the delayed release the encapsulant should be a minimum of about 20% of the coated active Preferably the encapsulant should be a minimum of about 30% of the coated active and most preferably should be a minimum of about 40% of the coated active Another method of giving a modified release of active agents such as caffeine and the other agents described herein is agglomeration with an agglomerating agent which partially coats the active agents This method includes the step of mixing active agents and an agglomerating agent with a small amount of water or solvent The mixture is prepared in such a way as to have individual wet particles in contact with each other so that a partial coating can be applied After the water or other solvent is removed the mixture is ground and used as a powdered active agent

Materials that can be used as the agglomerating agent are the same as those used in encapsulation mentioned previously Some of the better agglomerating agents for delayed release are the organic polymers like acrylic polymers and copolymers polyvinyl acetate polyvinylpyrrolidone waxes, shellac and Zein Other agglomerating agents are not as effective in giving a delayed release as are the polymers waxes shellac and Zein but can be used to give some delayed release Other agglomerating agents include but are not limited to agar alginates a wide range of water soluble cellulose derivatives like ethyl cellulose methyl cellulose sodium hydroxymethyl cellulose hydroxypropylmethyl cellulose dextrin gelatin modified starches and vegetable gums like guar gum locust bean gum and carrageenan Even though the agglomerated active agent such as caffeine is only partially coated when the quantity of coating is increased compared to the quantity of the active agent the release can also be modified The level of coating used in the agglomerated product is a minimum of about 5% Preferably, the coating level is a minimum of about 15% and more preferably about 20% Depending on the agglomerating agent a higher or lower amount of agent may be needed to give the desired release of the active agent

Caffeine or other active agents may be coated in a two-step process or a multiple step process Caffeine or other active agents may be encapsulated with any of the materials as described previously and then the encapsulated caffeine or other active agents can be agglomerated as previously described to obtain an encapsulated/agglomerated/caffeine or other active agent product that could be used in chewing gum to give a delayed release of the caffeine or other active agent

In another embodiment of this invention, caffeine or other active agent may be absorbed onto another component which is porous and become entrapped in the matrix of the porous component Common materials used for absorbing caffeine or other active agent include, but are not limited to, silicas silicates pharmasorb clay, sponge-like beads or microbeads, amorphous carbonates and hydroxides including aluminum and calcium lakes, all of which result in a delayed release of caffeine or other active agent Depending on the type of absorbent materials and how it is prepared, the amount of caffeine or other active agent that can be loaded onto the absorbent will vary Generally materials like polymers or sponge-like beads or microbeads amorphous sugars and alditols and amorphous carbonates and hydroxides absorb about 10% to about 40% of the weight of the absorbent Other materials like silicas and pharmasorb clays may be able to absorb about 20% to about 80% of the weight of the absorbent The general procedure for absorbing caffeine or other active agent onto the absorbent is as follows An absorbent like fumed silica powder can be mixed in a powder blender and a solution of caffeine or other active agent can be sprayed onto the powder as mixing continues The aqueous solution can be about 1 to 2% solids and higher solid levels to 15-30% may be used if temperatures up to 90°C are used Generally water is the solvent but other solvents like alcohol could also be used if approved As the powder mixes the liquid is sprayed onto the powder Spraying is stopped before the mix becomes damp The still free-flowing powder is removed from the mixer and dried to remove the water or other solvent, and is then ground to a specific particle size

After the caffeine or other active agent is absorbed or fixed onto an absorbent, the fixative/active agent can be coated by encapsulation Either full or partial encapsulation may be used depending on the coating composition used in the process Full encapsulation may be obtained by coating with a polymer as in spray drying, spray chilling, fluid-bed coating, coacervation or any other standard technique A partial encapsulation or coating can be obtained by agglomeration of the fixative/active agent mixture using any of the materials discussed above

Another form of encapsulation is by entrapment of an ingredient by fiber extrusion or fiber spinning into a polymer Polymers that can be used for extrusion are PVAC hydroxypropyl cellulose, polyethylene and other types of plastic polymers A process of encapsulation by fiber extrusion is disclosed in

U S Patent No 4 978 537 which is hereby incorporated by reference The water insoluble polymer may be preblended with caffeine or other active agents prior to fiber extrusion or may be added after the polymer is melted As the extrudate is extruded it results in small fibers that are cooled and ground This type of encapsulation/entrapment generally gives a very long, delayed release of an active ingredient

The four primary methods to obtain a treated caffeine or other active agent are (1 ) encapsulation by spray drying fluid-bed coating spray chilling and coacervation to give full or partial encapsulation (2) agglomeration to give partial encapsulation (3) fixation or absorption which also gives partial encapsulation and (4) entrapment into an extruded compound These four methods combined in any usable manner which physically modifies caffeine or other active agents dissolvability or modifies the release of caffeine or other active agents are included in this invention

After the active agent is treated it is used in the coating/panning of a pellet chewing gum Pellet or ball gum is prepared as conventional chewing gum but formed into pellets that are pillow shaped or into balls The pellets/balls can then be sugar coated or panned by conventional panning techniques to make a unique sugar coated pellet gum Treated active agent(s) can be easily dispersed in a sugar solution prepared for sugar panning Preferably, treated active agent(s) can be added as a powder blended with other powders often used in some types of conventional panning procedures often called dry charging The weight of the coating may be about 20% to about 50% of the weight of the finished gum product but higher levels of coating may be used when high doses of active agents are needed

Conventional panning procedures generally coat with sucrose, but recent advances in panning have allowed the use of other carbohydrate materials to be used in the place of sucrose Some of these components include, but are not limited to, dextrose, maltose, palatinose, xylitol, lactitol, maltitol, hydrogenated isomaltulose and other new alditols or a combination thereof These materials may be blended with panning modifiers including, but not limited to, gum arable gum talha maltodextπns, corn syrup, gelatin cellulose type materials like carboxymethyl cellulose or hydroxymethyl cellulose, starch and modified starches vegetable gums like alginates locust bean gum, guar gum and gum tragacanth, insoluble carbonates like calcium carbonate or magnesium carbonate and talc Antitack agents may also be added as panning modifiers which allow for the use of a variety of carbohydrates and sugar alcohols in the development of new panned or coated gum products Flavors sweeteners and cooling agents may also be added with the coating and with treated active agents to yield unique product characteristics The previously described encapsulated agglomerated or absorbed active agent may readily be coated onto a chewing gum composition The remainder of the chewing gum ingredients are non-critical to the present invention That is the treated particles of active agent can be coated onto conventional chewing gum formulations in a conventional manner Treated active agent may be coated onto a sugar chewing gum or a sugarless chewing gum In general a chewing gum composition typically comprises a water- soluble bulk portion a water-insoluble chewable gum base portion and typically water-insoluble flavoring agents The water-soluble portion dissipates with a portion of the flavoring agent 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 waxes softeners and inorganic fillers Elastomers may include polyisobutylene isobutylene-isoprene copolymer and styrene butadiene rubber as well as natural latexes such as chicle Resins include polyvinylacetate and terpene resins Fats and oils may also be included in the gum base, including tallow, hydrogenated and partially hydrogenated vegetable oils, and cocoa butter Commonly employed waxes include paraffin, microcrystalline and natural waxes such as beeswax and carnauba According to the preferred embodiment of the present invention, the insoluble gum base constitutes between about 5% and about 95% by weight of the gum More preferably the insoluble gum base comprises between about 10% and about 50% by weight of the gum, and most preferably between about 20% and about 45% by weight of the gum When high levels of gum coatings are needed gum base may comprise up to 95% of the gum center formula The gum base typically also includes a filler component The filler component may be calcium carbonate, magnesium carbonate, talc, dicalcium phosphate or the like The filler may constitute between about 5% and about 60% by weight of the gum base Preferably the filler comprises about 5% to about 50% by weight of the gum base

Gum bases typically also contain softeners including glycerol monostearate and glycerol triacetate Further gum bases may also contain optional ingredients such as antioxidants colors and emulsifiers The present invention contemplates employing any commercially acceptable gum base

The water-soluble portion of the chewing gum may further comprise softeners sweeteners flavoring agents and combinations thereof Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum Softeners also known in the art as plasticizers or plasticizing agents generally constitute between about 0 5% and about 15% by weight of the chewing gum Softeners contemplated by the present invention include glycerin, lecithin and combinations thereof Further, aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolyzates, corn syrup and combinations thereof may be used as softeners and binding agents in gum

As mentioned above, the treated active agent of the present invention may be used in sugar or sugarless gum formulations Sugar sweeteners generally include saccha de-containing components commonly known in the chewing gum art which comprise, but are not limited to, sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, galactose, corn syrup solids and the like, alone or in any combination Sugarless sweeteners include components with sweetening characteristics but which are devoid of the commonly known sugars and comprise but are not limited to sugar alcohols such as sorbitol mannitol xylitol, hydrogenated starch hydrolyzates, maltitol and the like alone or in any combination

Depending on the particular active agent release profile, the treated active agent of the present invention can also be used in combination with uncoated high-potency sweeteners or with high-potency sweeteners coated with other materials and by other techniques Also, untreated active agents could be added to the coating

A flavoring agent may also be present in the chewing gum in an amount within the range of from about 0 1 % to about 10% preferably from about 0 5% to about 5% by weight of the gum The flavoring agents may comprise 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 clove oil oil of wintergreen anise and the like Artificial flavoring components are also contemplated for use in gums of the present invention Those skilled in the art will recognize that natural and artificial flavoring agents may be combined in any sensorally acceptable blend All such flavors and flavor blends are contemplated by the present invention

Optional ingredients such as colors emulsifiers and other pharmaceutical agents may be added to the chewing gum

In general chewing gum is manufactured by sequentially adding the various chewing gum ingredients to a commercially available mixer known in the art After the ingredients have been thoroughly mixed, the gum mass is discharged from the mixer and shaped into the desired form such as extruding into chunks or casting into pellets which are then coated or panned

Generally, the ingredients are mixed by first melting the gum base and adding it to the running mixer The base may also be melted in the mixer itself Color or emulsifiers may also be added at this time A softener such as glycerin may also be added at this time, along with syrup and a portion of the bulking agent Other optional ingredients are added to the batch in a typical fashion well known to those of ordinary skill in the art The entire mixing procedure typically takes from five to fifteen minutes, but longer mixing times may sometimes be required Those skilled in the art will recognize that many variations of the above described procedure may be followed

As noted above the coating may contain ingredients such as flavoring agents as well as artificial sweeteners and dispersing agents coloring agents film formers and binding agents Flavoring agents contemplated by the present invention include those commonly known in the art such as 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 The flavoring agents may be used in an amount such that the coating will contain from about 0 2% to about 3% flavoring agent, and preferably from about 0 7% to about 2 0% flavoring agent

Artificial sweeteners contemplated for use in the coating include but are not limited to synthetic substances saccharin thaumatin alitame saccharin salts, aspartame sucralose and acesulfame-K The artificial sweetener may be added to the coating syrup in an amount such that the coating will contain from about 0 05% to about 0 5% and preferably from about 0 10% to about 0 3% artificial sweetener

Dispersing agents are often added to syrup coatings for the purpose of whitening and tack reduction Dispersing agents contemplated by the present invention to be employed in the coating syrup include titanium dioxide, talc, or any other antistick compound Titanium dioxide is a presently preferred dispersing agent of the present invention The dispersing agent may be added to the coating syrup in amounts such that the coating will contain from about 0. 1 % to about 1 0%, and preferably from about 0 3% to about 0 6% of the agent

Coloring agents are preferably added directly to the syrup in the dye or lake form Coloring agents contemplated by the present invention include food quality dyes Film formers preferably added to the syrup include methyl cellulose gelatins hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose carboxymethyl cellulose and the like and combinations thereof Binding agents may be added either as an initial coating on the chewing gum center or may be added directly into the syrup Binding agents contemplated by the present invention include gum arable, gum talha (another type of acacia) alginate, celiulosics, vegetable gums and the like

The coating is initially present as a liquid syrup which contains from about 30% to about 80% or 85% of the coating ingredients previously described herein, and from about 15% or 20% to about 70% of a solvent such as water In general, the coating process is carried out in a rotating pan Sugar or sugarless gum center tablets to be coated are placed into the rotating pan to form a moving mass The material or syrup which will eventually form the coating is applied or distributed over the gum center tablets Flavoring agents may be added before during and after applying the syrup to the gum centers Once the coating has dried to form a hard surface, additional syrup additions can be made to produce a plurality of coatings or multiple layers of hard coating

In a hard coating panning procedure, syrup is added to the gum center tablets at a temperature range of from about 100°F to about 240°F Preferably, the syrup temperature is from about 130°F to about 200°F throughout the process in order to prevent the poiyol or sugar in the syrup from crystallizing The syrup may be mixed with, sprayed upon, poured over, or added to the gum center tablets in any way known to those skilled in the art

In general, a plurality of layers is obtained by applying single coats, allowing the layers to dry, and then repeating the process The amount of solids added by each coating step depends chiefly on the concentration of the coating syrup Any number of coats may be applied to the gum center tablet. Preferably, no more than about 75 coats are applied to the gum center tablets More preferably, less than about 60 coats are applied and most preferably, about 30 to about 60 coats are applied In any event, the present invention contemplates applying an amount of syrup sufficient to yield a coated comestible containing about 10% to about 65% coating Preferably, the final product will contain from about 20% to about 50% coating Where higher dosage of an active agent is needed, the final product may be higher than 50% coating Those skilled in the art will recognize that in order to obtain a plurality of coated layers a plurality of premeasured aliquots of coating syrup may be applied to the gum center tablets It is contemplated however, that the volume of aliquots of syrup applied to the gum center tablets may vary throughout the coating procedure Once a coating of syrup is applied to the gum center tablets, the present invention contemplates drying the wet syrup in an inert medium A preferred drying medium comprises air Preferably forced drying air contacts the wet syrup coating in a temperature range of from about 70° to about 1 15°F More preferably the drying air is in the temperature range of from about 80° to about 100°F The invention also contemplates that the drying air possess a relative humidity of less than about 15 percent Preferably, the relative humidity of the drying air is less than about 8 percent

The drying air may be passed over and admixed with the syrup coated gum centers in any way commonly known in the art Preferably, the drying air is blown over and around or through the bed of the syrup coated gum centers at a flow rate, for large scale operations, of about 2800 cubic feet per minute If lower quantities of material are being processed, or if smaller equipment is used lower flow rates would be used

For many years, flavors have been added to a sugar coating of pellet gum to enhance the overall flavor of gum These flavors include spearmint flavor peppermint flavor, wintergreen flavor, and fruit flavors These flavors are generally preblended with the coating syrup just prior to applying it to the core or added together to the core in one or more coating applications in a revolving pan containing the cores Generally, the coating syrup is very hot, about 150° to 200°F, and the flavor may volatilize if preblended with the coating syrup too early The concentrated coating syrup is applied to the gum cores as a hot liquid the sugar or poiyol allowed to crystallize and the coating then dried with warm, dry air This is repeated in about 30 to 80 applications to obtain a hard shell coated product having an increased weight gain of about 50% A flavor is applied with one, two three or even four or more of these coating applications Each time flavor is added several non-flavored coatings are applied to cover the flavor before the next flavor coat is applied This reduces volatilization of the flavor during the coating process

For mint flavors such spearmint peppermint and wintergreen, some of the flavor components are volatilized but sufficient flavor remains to give a product having a strong, high impact flavor Fruit flavors that may contain esters are more easily volatilized and may be flammable and/or explosive and therefore generally these type of fruit flavors are not used in coatings In a preferred embodiment of this invention, a treated active agent such as caffeine is preblended with a gum arable solution to become a paste and then applied to the cores To reduce stickiness, the preblend may be mixed with a small amount of coating syrup before being applied Forced air drying is then continued as the gum arable binds the treated active agent to the cores Then additional coatings are applied to cover the treated active agent and imbed the treated active agent in the coatings

Gum Formulation Examples

The following examples of the invention and comparative examples are provided by way of explanation and illustration

As noted earlier the gum formulas can be prepared as stick or tab products in the sugar or sugarless type formulations These formulas can also be made in a pellet or pillow shape pellet or a round ball or any other shape of product for coating/panning However, gum formulas for pellet centers are generally adjusted to a higher level of gum base to give a more consumer acceptable size of gum bolus

Keeping this in mind, if a coating of about 25% of the total product is added to a pellet core as sugar or polyols, the gum base in the pellet core should also be increased by 25% Likewise, if a 33% coating is applied, the base levels should also be increased by 33% As a result, gum centers are usually formulated with about 25% to about 40% gum base with a corresponding decrease in the other ingredients except flavor Generally flavors increase with the level of gum base as the base tends to bind flavors into the gum and more flavor is needed to give a good flavorful product However flavors can also be added to the coating to give increased flavor impact and more flavor perception

Some typical sugar type gum center formulations are shown in Table 1 TABLE 1 (WEIGHT PERCENT)

EX 1 EX 2 EX 3 EX 4 EX 5 EX 6

SUGAR 520 490 480 440 410 390

GUM BASE 260 300 350 260 300 350

CORN SYRUP 200 190 150 180 170 140

GLYCERIN 10 10 10 10 10 10

PEPPERMINT 10 10 10 10 10 10

FLAVOR

DEXTROSE - . - 100 100 100

MONOHYDRATE

Encapsulated caffeine can then be used in the coating formula on the various pellet gum formulations The following Table 2 shows some sugar and dextrose type formulas

TABLE 2 (DRY WEIGHT PERCENT)

EX 7 EX 8 EX 9 EX 10 EX 11 EX 12

SUGAR 951 944 931 949 941 926

GUM TALHA 20 30 40 20 30 40

TITANIUM 05 10 10 — — —

DIOXIDE

CALCIUM — — — 05 10 20

CARBONATE

FLAVOR 03 05 08 05 08 03

WAX 01 01 01 01 01 01

ACTIVE 20 10 10 20 10 10

ENCAPSULATED

CAFFEINE

Table 2 (cont.)

EX 13 EX 14 EX 15 EX 16

DEXTROSE 96 6 94 4 96 2 93 5

MONOHYDRATE

GUM TALHA 1 5 3 0 1 5 3 0

TITANIUM 0 5 1 0 — ..

DIOXIDE

CALCIUM — -- 1 0 2 0

CARBONATE

FLAVOR 0 3 0 5 0 2 0 4

WAX 0 1 0 1 0 1 0 1

ACTIVE 1 0 1 0 1 0 1 0

ENCAPSULATED

CAFFEINE

The above formulations are made by making a syrup by dissolving the sugar and gum talha in solution at about 75% solids at boiling, and suspending titanium dioxide or calcium carbonate in this syrup Encapsulated caffeine and flavor are not mixed with the hot syrup, but added at low levels with one or more coats After the final coats are applied and dried, wax is applied to give a smooth polish This process gives a hard shell coating

A dry charge blend of powdered sugar, dextrose monohydrate or gum talha may be used When encapsulated caffeine is added to the coating, it may be preblended with the dry charge material The dry charge powder material is applied to the surface after the liquid syrup to help dry the surface before applying another coating A dry charge may be used to build up a coating but then finished with a straight syrup to obtain a hard shell Table 3 gives these types of formulas

TABLE 3 (DRY WEIGHT PERCENT)

EX 17 EX 18 EX 19 EX 20 EX 21 EX 22

SUGAR 75 5 80 4 — - 85 5 —

DEXTROSE - - 76 5 85 3 - 85 1 MONOHYDRATE

POWDERED 20 0^* 15 0^* - - - - SUGAR

POWDER — — 20 0^* 10 0^* — - DEXTROSE

GUM TALHA 2 0 3 0 2 0 3 0 8 0^* 8 0* POWDER

GUM TALHA - — - — 4 0 4 0 SOLUTION

FLAVOR 0 4 0 5 0 4 0 6 0 4 0 8

WAX 0 1 0 1 0 1 0 1 0 1 0 1

ACTIVE 2 0 1 0 1 0 1 0 2 0 2.0

ENCAPSULATED

CAFFEINE

^*Powder and/or crystalline sugar or gum talha blended with encapsulated caffeine may be used

In Examples 17-20, gum talha is blended in the sugar syrup. In Examples 21 and 22, gum talha powder is dry charged after a gum talha solution is applied in the first stages of coating, then this is followed by a hard shell coating of sugar solution or dextrose solution

Encapsulated caffeine may also be preblended with gum talha solution to form a paste and to assist in drying when mixed with coating syrup. Preferably this should be done when the encapsulant is water insoluble. The gum talha/ encapsulated caffeine should also be applied to the coating immediately after being preblended.

Gum talha may also be used in coating of sugarless gum centers Like sugar gum centers, the base formulation can be increased in proportion to the amount of coating applied to the center Formulations for low and high moisture gum can be used to make gum centers Generally, the base level may be increased to 30-46% with the other ingredients proportionally reduced Some typical gum formulas are in Table 4 TABLE 4 (WEIGHT PERCENT)

EX 23 EX 24 EX 25 EX 26 EX 27 EX. 28 EX. 29

GUM BASE 35.0 35.0 30.0 30.0 30 0 40.0 30 0

CALCIUM - - 5.0 10.0 15.0 - - CARBONATE

SORBITOL 43 3 45 3 46 3 40 3 44 8 41 7 46.5

MANNITOL 10 0 10 0 5.0 10 0 - 8.0 10.0

GLYCERIN - 8 0 2.0 - 8.0 2.0 2.0

SORBITOL 10 0 - 10.0 8.0 - 6.0^a) 10.0^a) LIQUID

FLAVOR 1 5 1.5 1.5 1.5 2.0 2.0 1.3

HIGH 0 2 0.2 0.2 0.2 0.2 0.3 0.2 INTENSITY

a) Lycasin brand hydrogenated starch hydrolyzate used instead of sorbitol liquid

In the above center formulations, the high intensity sweetener used is aspartame. However other high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness

Lycasin and other polyols such as maltitol, xylitol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels. The texture may be adjusted by varying glycerin or sorbitol liquid Sweetness of the center formulation can also be adjusted by varying the level of high intensity sweetener

Gum talha is especially useful in sugarless coatings with xylitol, sorbitol, maltitol lactitol, hydrogenated isomaltulose and erythntol Gum talha acts as a binder film former and hardener of the coated pellet The following table gives formulas for a xylitol coating with encapsulated caffeine TABLE 5

(DRY WEIGHT PERCENT)

EX 30 EX 31 EX 32 EX 33 EX 34 EX 35

XYLITOL 938 914 897 891 889 878

GUM TALHA 40 60 70 85 85 100

FLAVOR 05 05 07 07 09 05

TITANIUM 05 09 - 05 05^** 05^** DIOXIDE

TALC 01 01 01 01 01 01

WAX 01 01 01 01 01 01

COLOR^* - - 14 - - -

ACTIVE 10 10 10 10 10 10

ENCAPSULATED

CAFFEINE

Lake color dispersed in xylitol solution

Calcium carbonate used in place of titanium dioxide

The above formulas are used to coat pellets by applying a xylitol/gum talha solution in multiple coats and air drying Color or whitener is also mixed in the solution After pellets have been coated and dried, talc and wax are added to give a polish

As in sugar coating, some of the gum talha powder may be blended with powder xylitol for dry charging Encapsulated caffeine may be added with the dry charge material Also, a gum talha syrup may be made and used as a separate coating with encapsulated caffeine and dry charged

Like xylitol, erythntol coating also requires a binder, film former, and hardener in the coating to make an acceptable product The following formulations can be made TABLE 6 (DRY WEIGHT PERCENT)

EX 36 EX 37 EX 38 EX 39 EX 40 EX 41

ERYTHRITOL 92 8 90 5 88 2 89 1 87 4 85 8

GUM TALHA 5 0 7 0 8 5 8 5 10 0 12 0

FLAVOR 0 5 0 4 0 7 0 7 0 9 0 5

TITANIUM 0 5 0 9 . 0 5 0 5 0 5

DIOXIDE

TALC 0 1 0 1 0 1 0 1 0 1 0 1

WAX 0 1 0 1 0 1 0 1 0 1 0 1

COLOR - - 1 4^* - - -

ACTIVE 1 0 1 0 1 0 1 0 1 0 1 0

ENCAPSULATED

CAFFEINE

^* Lake color dispersed in erythntol solution

The above formulas are used to coat pellets by applying a erythπtol/gum talha solution in multiple coats and air drying Color or whitener is also mixed in the solution After pellets have been coated and dried, talc and wax are added to give a polish

As in xylitol coating, some of the gum talha powder may be blended with powder erythntol for dry charging Encapsulated caffeine may be added with the dry charge material Also, a gum talha syrup may be made and used as a separate coating with encapsulated caffeine and dry charged

For coating formulas based on sorbitol, maltitol, lactitol, and hydrogenated isomaltulose, gum talha can be used as a binder and film former, and a crystallization modifier to help facilitate coating Generally these polyols are more difficult to coat using only a straight syrup, but with proper technique a good smooth hard shell can be made However, it may be preferable to add a dry charge to quicken the drying process before the pellets get too sticky As above encapsulated caffeine can be added with the dry charge The following formulations may be used TABLE 7 (DRY WEIGHT PERCENT)

EX 42 EX 43 EX 44 EX 45 EX 46 EX 47

SORBITOL 93 8 90 9 86 1 85 8 75 1 68 5

SORBITOL 2 0 3 0 5 0 10 0 20 0 25 0

POWDER

GUM TALHA 2 0 4 0 6 0 2 0 3 0 4 0

FLAVOR 0 5 0 4 0 7 0 5 0 3 0 7

TITANIUM 0 5 0 5 1 0 0 5 0 4 0 6

DIOXIDE

TALC 0 1 0 1 0 1 0 1 0 1 0 1

WAX 0 1 0 1 0 1 0 1 0 1 0 1

ACTIVE 1 0 1 0 1 0 1 0 1 0 1 0

ENCAPSULATED

CAFFEINE

Sorbitol powder is used to dry charge in the early stages of coating Sorbitol, gum talha, and whitener is blended into a syrup and applied to pellets After all coating is applied and dried, talc and wax are added to give a polish

In a similar manner, coatings with maltitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 7 by replacing sorbitol with any one of the other polyols and sorbitol powder with the poiyol powder Like sorbitol the other polyols may become sticky during the coating and drying process, so the dry powder charge with encapsulated caffeine may be needed to give the proper drying In the later stages of the coating process less gum talha could be used and a more pure poiyol syrup could be used to give a smooth surface Also, the dry charge would only be used in the early stages of the coating process A gum talha syrup may be made and used as a separate coating with encapsulated caffeine and dry charged

In addition to dry charging with the specific poiyol, other ingredients may be added to the dry charge to help absorb moisture These materials could be inert such as talc, calcium carbonate, magnesium carbonate, starches, gums like gum talha or other moisture absorbing materials Also, powdered sweeteners or flavors could be added with the dry charge Some polyols such as sorbitol, maltitol, lactitol, or hydrogenated isomaltulose are not sufficiently sweet compared to sugar or xylitol, so high intensity sweeteners may be added to the coating such as aspartame, acesulfame K, salts of acesulfame cyclamate and its salts, saccharin and its salts, alitame, sucralose, thaumatin, monelhn, dihydrochalcone, glycyrrhizin, and combinations thereof If a hot syrup is applied heat may degrade the sweetener so only stable sweeteners should be used Generally high intensity sweeteners are added with the polyol/gum talha solution to obtain an even distribution in the coatings

Liquid flavors generally are not added throughout the coating but at specific points throughout the process When flavor is added, less air is used for drying until the flavor coating is covered by the next coatings and dried Flavors may be various spearmint, peppermint, wintergreen, cinnamon, and fruit flavors to yield a wide variety of flavored chewing gum products

For examples 48 and 49, the following sugar gum center formulation was made into pellet gum centers as 1 gram pieces.

Comparative Example 48

The following formulas were used to prepare coating syrups for this example

Free caffeine was dissolved in coating Syrup 1 and applied to about 12,000 grams of gum centers until a coating of about 0.3 grams per piece had been formed. Because of the limited solubility of caffeine in the coating syrup, and the need for higher levels of caffeine in the final product, four applications of an additional 18 grams of caffeine each, mixed with 100 grams of Syrup 1 to form a slurry, were poured into the coating pan. Thus 203 grams of caffeine was applied. Thereafter the coating was finished with Syrup 2 to achieve a 1.5 gram piece weight, with a total yield of 18,000 grams of coated product. The theoretical percentage of caffeine in the final product was about 1.13%.

Example 49

The following formulas were used to prepare coating syrups for this example:

The encapsulated caffeine used in Syrup 3 was made by fluid bed coating caffeine with an alcoholic/Zein mixture to give an 80% active caffeine/20% Zein. This material was blended with a 40% solution of gum arable and some of Syrup 3 at a ratio of 60 parts encapsulated caffeine to 100 parts gum arable solution to 100 parts Syrup 3 to form a slurry, and applied in four stages with coating Syrup 3 to achieve a piece weight of about 1 3 grams The total active caffeine applied was about 192 grams The gum was finished with Syrup 4 to achieve a piece weight of about 1 5 gram The theoretical percentage of caffeine in the final product was about 1 07% An analysis of the product showed an actual caffeine level of 1 13%

Examples 48 and 49 were sensory tested in a time-intensity test by a nine-member panel using a 10 point scale and judged for bitterness intensity, flavor intensity, and sweetness intensity Results for bitterness intensity are shown in Figure 1 Significant difference was found at minutes 1 , 2, 3, 4 and 5 for bitterness intensity, but no difference was found for flavor or sweetness intensity

Using the gum center formulas of Table I, encapsulated ibuprofen can then be used in the coating formula on the various pellet gum formulations

Dosage for 2-5% ibuprofen in coating is 60 to 150 mg per 2-1 5 gram pieces. The following Table 8 shows some sugar and dextrose type formulas

TABLE 8 (DRY WEIGHT PERCENT)

EX 50 EX 51 EX 52 EX 53 EX 54 EX 55

SUGAR 92 1 93 4 92 1 91 9 93 1 91 6

GUM TALHA 2 0 3 0 4 0 2 0 3 0 4 0

TITANIUM 0 5 1 0 1 0 — — —

DIOXIDE

CALCIUM — ~ — 0 5 1 0 2 0

CARBONATE

FLAVOR 0 3 0 5 0 8 0 5 0 8 0 3

WAX 0 1 0 1 0 1 0 1 0 1 0 1

ACTIVE 5 0 2 0 2 0 5 0 2 0 2 0

ENCAPSULATED

IBUPROFEN Table 8 (cont.)

EX 56 EX 57 EX 58 EX 59

DEXTROSE 94 6 92 4 94 2 89 5

MONOHYDRATE

GUM TALHA 1 5 3 0 1 5 3 0

TITANIUM 0 5 1 0 — —

DIOXIDE

CALCIUM — — 1 0 2 0

CARBONATE

FLAVOR 0 3 0 5 0 2 0 4

WAX 0 1 0 1 0 1 0 1

ACTIVE 3 0 3 0 3 0 5 0

ENCAPSULATED

IBUPROFEN

The above formulations are made by making a syrup by dissolving the sugar and gum talha in solution at about 75% solids at boiling, and suspending titanium dioxide or calcium carbonate in this syrup Encapsulated ibuprofen and flavor are not mixed with the hot syrup, but added at low levels with one or more coats After the final coats are applied and dried, wax is applied to give a smooth polish This process gives a hard shell coating

A dry charge blend of powdered sugar, dextrose monohydrate or gum talha may be used When encapsulated ibuprofen is added to the coating, it may be preblended with the dry charge material The dry charge powder material is applied to the surface after the liquid syrup to help dry the surface before applying another coating A dry charge may be used to build up a coating, but then finished with a straight syrup to obtain a hard shell Table 9 gives these types of formulas

TABLE 9 (DRY WEIGHT PERCENT)

EX 60 EX 61 EX 62 EX 63 EX 64 EX 65

SUGAR 72 5 79 4 - - 82 5 —

DEXTROSE — - 75 5 84 3 ~ 84 1 MONOHYDRATE

POWDERED 20 0^* 15 0^* - - - - SUGAR

POWDER ~ - 20 0^* 10 0^* - - DEXTROSE

GUM TALHA 2 0 3 0 2 0 3 0 8 0^* 8 0^* POWDER

GUM TALHA — - - - 4 0 4 0 SOLUTION

FLAVOR 0 4 0 5 0 4 0 6 0 4 0 8

WAX 0 1 0 1 0 1 0 1 0 1 0 1

ACTIVE 5 0 2 0 2 0 2 0 5 0 3 0

ENCAPSULATED

IBUPROFEN

^*Powder and/or crystalline sugar or gum talha blended with encapsulated ibuprofen may be used

In Examples 60-63, gum talha is blended in the sugar syrup In Examples 64 and 65, gum talha powder is dry charged after a gum talha solution is applied in the first stages of coating, then this is followed by a hard shell coating of sugar solution or dextrose solution

Encapsulated ibuprofen may also be preblended with gum talha solution to form a paste, and to assist in drying when mixed with coating syrup Preferably this should be done when the encapsulant is water insoluble The gum talha/ encapsulated ibuprofen should also be applied to the coating immediately after being preblended

Gum talha is especially useful in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythntol Gum talha acts as a binder, film former and hardener of the coated pellet The following table gives formulas for a xylitol coating with encapsulated ibuprofen TABLE 10 (DRY WEIGHT PERCENT)

EX 66 EX 67 EX 68 EX 69 EX 70 EX 71

XYLITOL 918 894 877 871 849 838

GUM TALHA 40 60 70 85 85 100

FLAVOR 05 05 07 07 09 05

TITANIUM 05 09 - 05 05^** 05^** DIOXIDE

TALC 01 01 01 01 01 01

WAX 01 01 01 01 01 01

COLOR* - - 14 - - -

ACTIVE 30 30 30 30 50 50

ENCAPSULATED

IBUPROFEN

Lake color dispersed in xylitol solution

Calcium carbonate used in place of titanium dioxide

The above formulas are used to coat pellets by applying a xylitol/gum talha solution in multiple coats and air drying Color or whitener is also mixed in the solution After pellets have been coated and dried, talc and wax are added to give a polish

As in sugar coating, some of the gum talha powder may be blended with powder xylitol for dry charging Encapsulated ibuprofen may be added with the dry charge material Also, a gum talha syrup may be made and used as a separate coating with encapsulated ibuprofen and dry charged

For coating formulas based on sorbitol, maltitol, lactitol, and hydrogenated isomaltulose, gum talha can be used as a binder and film former, and a crystallization modifier to help facilitate coating Generally these polyols are more difficult to coat using only a straight syrup, but with proper technique a good smooth hard shell can be made However it may be preferable to add a dry charge to quicken the drying process before the pellets get too sticky As above, encapsulated ibuprofen can be added with the dry charge The following formulations may be used TABLE 11 (DRY WEIGHT PERCENT)

EX 72 EX 73 EX 74 EX 75 EX 76 EX 77

SORBITOL 918 889 841 838 731 665

SORBITOL 20 30 50 100 180 230 POWDER

GUM TALHA 20 40 60 20 30 40

FLAVOR 05 04 07 05 03 07

TITANIUM 05 05 10 05 04 06 DIOXIDE

TALC 01 01 01 01 01 01

WAX 01 01 01 01 01 01

ACTIVE 30 30 30 30 50 50

ENCAPSULATED

IBUPROFEN

Sorbitol powder is used to dry charge in the early stages of coating Sorbitol, gum talha, and whitener is blended into a syrup and applied to pellets After all coating is applied and dried, talc and wax are added to give a polish

In a similar manner, coatings with maltitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 11 by replacing sorbitol with any one of the other polyols and sorbitol powder with the poiyol powder Like sorbitol the other polyols may become sticky during the coating and drying process, so the dry powder charge with encapsulated ibuprofen may be needed to give the proper drying In the later stages of the coating process less gum talha could be used and a more pure poiyol syrup could be used to give a smooth surface Also, the dry charge would only be used in the early stages of the coating process A gum talha syrup may be made and used as a separate coating with encapsulated ibuprofen and dry charged In addition to dry charging with the specific poiyol, other ingredients may be added to the dry charge to help absorb moisture These materials could be inert such as talc, calcium carbonate magnesium carbonate, starches, gums like gum talha or other moisture absorbing materials Also, powdered sweeteners or flavors could be added with the dry charge Some polyols such as sorbitol, maltitol lactitol, or hydrogenated isomaltulose are not sufficiently sweet compared to sugar or xylitol, so high intensity sweeteners may be added to the coating such as aspartame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts alitame sucralose, thaumatin, monellin dihydrochalcone glycyrrhizin, and combinations thereof If a hot syrup is applied, heat may degrade the sweetener so only stable sweeteners should be used Generally high intensity sweeteners are added with the polyol/gum talha solution to obtain an even distribution in the coatings

Encapsulation Examples

Although a wide variety of medicaments may be encapsulated, encapsulation of caffeine is demonstrated in the next examples For spray drying, the solids level of an aqueous or alcoholic solution can be about 5- 30%, but preferred levels are indicated in the examples listed Example A - An 80% shellac, 20% active caffeine powder mixture is obtained by spray drying an alcohol/shellac/caffeine solution at total solids of 10%

Example B - A 50% shellac, 50% active caffeine powder mixture is obtained by spray drying an appropriate ratio of alcohol/shellac/caffeine solution at 10% solids

Example C - A 70% Zein, 30% active caffeine powder mixture is obtained by spray drying an alcohol/Zein/caffeine solution at 10% solids

Example D - A 40% shellac, 60% active caffeine powder mixture is obtained by fluid-bed coating caffeine with an alcohol/shellac solution at 30% solids

Example E - A 20% Zein, 80% active caffeine powder mixture is obtained by fluid-bed coating caffeine with an alcohol/Zein solution at 30% solids

Example F - A 40% Zein, 60% active caffeine powder mixture is obtained by fluid-bed coating caffeine with an alcohol/Zein solution at 25% solids Example G - An 85% wax, 15% active caffeine powder mixture is obtained by spray chilling a mixture of molten wax and caffeine

Example H - A 70% wax, 30% active caffeine powder mixture is obtained by spray chilling a mixture of molten wax and caffeine Example J - A 70% Zein, 30% active caffeine powder mixture is obtained by spray drying a hot aqueous mixture of caffeine and Zein dispersed in an aqueous, high-pH (pH of 1 1 6-12 0) media at 10% solids

Example K - A 20% Zein, 80% active caffeine powder mixture is obtained by fluid-bed coating caffeine with an aqueous, high-pH (pH=1 1 6- 12 0) Zein dispersion of 10% solids

Example L - A 20% Zein, 20% shellac, 60% active caffeine powder mixture is obtained by spray drying an alcohol/shellac/caffeine mixture and then fluid-bed coating the spray dried product for a second coating of alcohol

Examples A to L would all give nearly complete encapsulation and would give reduced bitterness in sugar and sugarless gum formulations The higher levels of coating would give more reduced bitterness than the lower levels of coating

Other polymers that are more water soluble and used in coating would give less bitterness of the caffeine in a gum coating

Example M - An 80% gelatin, 20% active caffeine powder mixture is obtained by spray drying a hot gelatin/caffeine solution at 20% solids

Example N - A 30% hydroxypropylmethyl cellulose (HPMC), 70% caffeine powder mixture is obtained by fluid-bed coating caffeine with an aqueous solution of HPMC at 10% solids

Example P - A 50% maltodextπn, 50% active caffeine powder mixture is obtained by spray drying a hot aqueous solution of caffeine and maltodextπn at 30% solids

Example Q - A 40% gum arable, 60% active caffeine powder mixture is obtained by fluid-bed coating caffeine with an aqueous solution of gum arable at 30% solids Caffeine could also be used in gum as an agglomerated caffeine to give some reduced bitterness in a gum coating Agglomerated caffeine can be prepared as in the following examples

Example R - A 15% hydroxypropylmethyl cellulose (HPMC), 85% active caffeine powder mixture is prepared by agglomerating caffeine and

HPMC blended together, with water being added, and the resulting product being dried and ground

Example S - A 15% gelatin, 85% active caffeine powder mixture is made by agglomerating caffeine and gelatin blended together, with water being added, and the resulting product being dried and ground

Example T - A 10% Zein, 90% active caffeine powder mixture is made by agglomerating caffeine with an alcohol solution containing 25% Zein, and drying and grinding the resulting product

Example V - A 15% shellac, 85% active caffeine powder mixture is made by agglomerating caffeine with an alcohol solution containing 25% shellac, and drying and grinding the resulting product

Example W - A 20% HPMC, 80% active caffeine powder mixture is obtained by agglomerating an HPMC and caffeine mixture blended together, with water being added, and the resulting product being dried and ground Example X - A 20% Zein, 80% active caffeine powder mixture is obtained by agglomerating caffeine and Zein dissolved in high-pH water (11 6-12 0) at 15% solids, with the resulting product being dried and ground

Example Y - A 20% wax, 80% active caffeine powder mixture is obtained by agglomerating caffeine and molten wax, and cooling and grinding the resulting product

Example Z - A 15% maltodextπn, 85% active caffeine powder mixture is obtained by agglomerating a blend of caffeine and maltodextπn, then adding water, drying and grinding

Multiple step agglomeration/encapsulation procedures can also be used in making release-modified caffeine for use in the formulations in previous tables Examples of multiple step treatments are here described Example AA - Caffeine is spray dried with maltodextπn at 30% solids to prepare a powder This powder is then agglomerated with a hydroxypropylmethyl cellulose (HPMC) in a ratio of 85/15 powder/HPMC, wetted with water and dried After grinding the resulting powder will contain about 68% active caffeine, 17% maltodextπn and 15% HPMC

Example BB - Caffeine is agglomerated with HPMC in a ratio of 85/15 caffeine/HPMC After drying and grinding, the resulting powder is fluid-bed coated with an alcohol/shellac solution at about 25% solids to give a final product containing about 60% active caffeine, 10% HPMC, and about 30% shellac

Example CC - Caffeine is agglomerated with HPMC in a ratio of 85/15 caffeine/HPMC After drying and grinding, the resulting powder is agglomerated with a 15% solids, high-pH, aqueous solution of Zein to give a final product containing about 60% active caffeine, 10% HPMC, and 30%

Example DD - Caffeine is spray dried with a 25% solution of gelatin The spray dried product is then agglomerated with a 15% solids, high-pH, aqueous solution of Zein The final product will contain about 50% active caffeine, 20% gelatin, and 30% Zein Example EE - Caffeine is agglomerated with molten wax in a ratio of

85/15 caffeine/wax When the mixture cools and is ground, it is fluid-bed coated with a 25% Zein - 75% alcohol solution, giving a final product containing 60% active caffeine, 10% wax and 30% Zein

These examples, when used in any of the formulations noted in previous tables, give caffeine a reduced bitterness These multiple step procedures can actually give more reduced bitterness than the single step processes Multiple step processes of more than two steps may give even more reduced bitterness, but may generally become less cost effective and less efficient Preferably, spray drying can be the first step with additional steps of fluid-bed coating, spray chilling and agglomeration being part of the latter steps For absorption type examples, the reduced bitterness of caffeine is dependent on the type of absorbing material Most materials like silicas, silicates, cellulose, carbonates and hydroxides would be expected to give a more reduced bitterness than amorphous sugar and sugar alcohols Some examples

Example FF - A hot 10% solution of caffeine is sprayed onto a precipitated silica to absorb the caffeine The mixture is ground and the final product is about 50% active caffeine

Example GG - A hot 10% solution of caffeine is sprayed onto a pharmasorb clay The mixture is dried and ground and gives a final product of about 80% clay and 20% active caffeine

Example HH - A 10% solution of caffeine is sprayed onto a microcrystalline cellulose powder The mixture is dried and ground and gives a product that is about 70% microcrystalline cellulose and 30% active caffeine

The caffeine can also be used with a variety of high-intensity sweeteners and blended together before encapsulation, agglomeration, absorption, and entrapment This can further reduce bitterness associated with caffeine Some examples are Example JJ - Caffeine and aspartame are blended together in a 2/1 ratio as a powder This mixture is then spray chilled with wax in a ratio of 60/40 mixture/wax to obtain a powder containing 40% caffeine, 20% aspartame, and 40% wax

Example KK - Caffeine and thaumatin in a 4/1 ratio are dissolved in water with a 10% solution of gelatin and spray dried This spray dried powder is then agglomerated with a high-pH aqueous 15% Zein solution The mixture is dried and ground and gives a product containing 40% caffeine, 10% thaumatin, 35% gelatin, and 15% Zein

Example LL - Caffeine and alitame in a 7/1 ratio are prepared in a hot 10% solution This solution is sprayed onto a high absorption silica powder

The mixture is dried, ground and fluid-bed coated with an alcohol/shellac mixture, giving a product that contains 35% caffeine 5% alitame 40% silica, and 20% shellac

Example MM - Caffeine and sodium cyclamate in a 1/1 ratio are blended together as a powder and then agglomerated with water and hydroxypropylmethyl cellulose (HPMC) This blend is dried ground and agglomerated further with a high-pH, aqueous 15% solution of Zein to obtain a product containing 34% sodium cyclamate, 34% caffeine, 12% HPMC and

Example NN - Caffeine and glycyrrhizin in a 1/1 ratio are blended together as a powder and fluid-bed coated with a solution of 25% shellac in alcohol The coated product is agglomerated further with water and hydroxypropylmethyl cellulose (HPMC) to obtain a product containing 30% caffeine, 30% glycyrrhizin, 25% shellac, and 15% HPMC

Example PP - Caffeine and sodium saccharin in a ratio of 1/1 are blended together as a powder and fluid bed coated with a solution of 25% shellac in alcohol The coated product is agglomerated further with water and hydroxypropylmethyl cellulose (HPMC) to obtain a product containing 30% caffeine, 30% sodium saccharin, 25% shellac, and 15% HPMC

If the blends of caffeine and other high-intensity sweeteners of above examples are added to gum coatings, a significant reduced caffeine bitterness would be expected This would improve the quality of flavor The following are examples of fiber extruded PVAC/caffeine blends to give a delayed release of caffeine and give reduced bitterness

Example QQ - Medium molecular weight PVAC and caffeine at a ratio of 3/1 are blended together as a powder and extruded The fibers are cooled and ground to give a product containing 75% PVAC and 25% caffeine

Example RR - Medium molecular weight PVAC, caffeine and aspartame at a ratio of 12/4/1 are blended together as a powder and extruded, the resulting fibers are ground and give a product containing 70% PVAC, 24% caffeine and 6% aspartame

Example SS - Medium molecular weight PVAC, caffeine, aspartame, and sodium glueonate at a ratio of 16/4/4/1 are blended together as a powder and extruded The fibers are ground and gives a product containing 64% PVAC, 16% caffeine 16% sodium glueonate, and 4% aspartame

Sodium glueonate is a bitterness inhibitor that can be mixed with caffeine before being encapsulated or entrapped This bitterness inhibitor, along with other bitterness inhibitors such as sodium salts of chloride, ascorbic acid, glutamic acid and citric acid, as well as other various organic compounds, can be added to caffeine to reduce bitterness

Example TT - A 20% hot aqueous solution of maltodextπn is mixed with a 40% hot solution of sodium glueonate Two liters of this mixture is combined with 100 grams of caffeine, dispersed and spray dried A final product containing 50% maltodextπn, 33% sodium glueonate and 17% caffeine is obtained

Example W - A 2400 ml quantity of a 25% hot aqueous solution of maltodextπn is mixed with 50 grams of aspartame to form a suspension To this is added a hot aqueous solution of 400 grams of sodium glueonate, 200 grams of caffeine, 1200 grams of hot water This mixture is spray dried to obtain a powder containing 48% maltodextπn, 32% sodium glueonate, 16% caffeine and 4% aspartame

Example WW - To a 2400 gram quantity of a 25% hot solution of maltodextπn, 200 grams of citric acid and 50 grams of aspartame are added and suspended To this mixture is added a hot aqueous solution of 400 grams of sodium glueonate, 200 grams of caffeine and 1200 grams of hot water This mixture is spray dried to obtain a powder containing 41 % maltodextπn, 28% sodium glueonate, 14% caffeine, 14% citric acid and 3% aspartame

It should be appreciated that the methods and compositions of the present invention are capable of being incorporated in the form of a variety of embodiments, only a few of which have been illustrated and described above The invention may be embodied in other forms without departing from its spirit or essential characteristics It will be appreciated that the addition of some other ingredients, process steps, materials or components not specifically included will have an adverse impact on the present invention The best mode of the invention may therefore exclude ingredients, process steps, materials or components other than those listed above for inclusion or use in the invention However, the described embodiments are to be considered in all respects only as illustrative and not restrictive, and the scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope

Claims

WE CLAIM

1 A method of producing a coated chewing gum containing a physically-modified active agent in order to modify the release of active agent in the mouth comprising the steps of a) mixing a quantity of the active agent with a modifying agent to produce a physically-modified active agent, b) adding a quantity of the physically-modified active agent to a chewing gum coating to provide a active agent level in gum of from about 50 micrograms to about 500 milligrams

2 The method of claim 1 wherein said modifying agent is an encapsulating agent

3 The method of claim 2 wherein the active agent and encapsulating agent are also mixed with a solvent and the resulting mixture is dried prior to being added to the chewing gum coating

4 The method of claim 3 wherein the encapsulating material is selected from the group consisting of maltodextπn, gum arable, Zein and shellac

5 The method of claim 3 wherein the mixture is spray dried and the solvent is selected from the group consisting of alcohol and water

6 The method in claim 3 wherein a high-potency sweetener selected from the group consisting of aspartame, alitame, salts of acesulfame, cyclamate and its salts, saccharine and its salts, thaumatin, monellin, dihydrochalcones and combinations thereof is mixed in the mixture in combination with the active agent

7 A chewing gum made according to the method of claim 3 8 The method according to claim 2 wherein the active agent is fluid-bed coated with a solution of encapsulating agent and solvent in order to modify the release of active agent in a chewing gum coating

9 The method of claim 8 wherein the solvent is selected from the group consisting of alcohol and water

10 The method of claim 8 wherein the encapsulating material is selected from the group consisting of shellac and Zein

11 The method of claim 8 wherein an additional high-potency sweetener selected from the group consisting of aspartame, alitame, salts of acesulfame, cyclamate and its salts, saccharin and its salts, thaumatin, monellin, dihydrochalcones and combinations thereof is mixed in the mixture in combination with the active agent

2 A chewing gum made according to the method of claim 8

13 The method according to claim 2 wherein the caffeine is encapsulated by coacervation in order to modify the release of active agent in chewing gum coating

14 The method of claim 2 wherein the active agent is mixed with a molten encapsulating agent and the active agent is encapsulated by spray chilling in order to modify the release of active agent in a chewing gum coating

15 The method of claim 14 wherein the encapsulating agent comprises wax

16 The method of claim 2 wherein the active agent is mixed with a polymer as the encapsulating agent and the resulting mixture is extruded into fine fibers in such a way as to encapsulate the active agent in order to modify the release of the active agent in the chewing gum coating 17 The method of claim 16 wherein the polymers are selected from the group consisting of PVAC, hydroxypropyl cellulose, polyethylene and plastic polymers

18 The method of claim 1 wherein the active agent is mixed with an absorbent as the modifying agent

19 The method of claim 1 wherein said active agent is selected from the group consisting of vitamins, analgesics, antacids, antihistamines, decongestants, anesthetics and stimulants

20 The method of claim 19 wherein said analgesics are selected from the group consisting of aspirin, acetaminophen, ketoprofen, naproxen, and ibuprofen

21 The method of claim 19 wherein said antacids are selected from the group consisting of cimetidine, ranitidine, omeprazole and famotidine

22 The method of claim 19 wherein said antihistamines are selected from the group consisting of cimetidine, ranitidine famotidine and chlorpheniramine

23 The method of claim 19 wherein said decongestants are selected from the group consisting of dextromethorphan, noscapine, and pseudoephedπne

24 The method of claim 19 wherein said stimulant is caffeine

25 The method of claim 1 wherein said active agent is nicotine or a nicotine susbtitute

26 A method of producing a coated chewing gum containing physically-modified active agent in order to modify the release of active agent comprising the steps of a) mixing a quantity of active agent with an agglomerating agent and a solvent to partially coat the active agent, b) removing the solvent from the mixture of active agent and agglomerating agent to form a dried material; and c) adding a quantity of the dried material to a chewing gum coating to provide a active agent level in gum of from about 50 micrograms to about 500 milligrams.

27. The method of claim 26 wherein the level of coating on the agglomerated active agent is at least about 5%.

28. The method of claim 26 wherein the level of coating on the agglomerated active agent is at least about 15%.

29. The method of claim 26 wherein the level of coating on the agglomerated active agent is at least about 20%.

30. The method of claim 26 wherein the dried material is ground to a powder prior to adding the dried material to the chewing gum.

31. The method of claim 26 wherein the active agent which has not been treated with a modifying agent is also added to the chewing gum coating.