CONTROLLING RELEASE OF ACTIVE AGENTS FROM A CHEWING GUM COATING

LIBERATION PROLONGEE DE PRINCIPES ACTIFS D'UN ENROBAGE DE GOMME A MACHER

English 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.

French Abstract

L'invention concerne un procédé permettant de produire une gomme à mâcher enrobée renfermant un principe actif à libération prolongée. Cette invention concerne également la gomme à mâcher ainsi produite, que l'on obtient en modifiant physiquement les propriétés dudit principe actif en soumettant celui-ci à un enrobage et à un séchage. Selon ce procédé, un principe actif est enrobé par encapsulation, partiellement enrobé par agglomération, piégé par absorption, ou traité par une succession d'étapes d'encapsulation, d'agglomération, et d'absorption. Ce principe actif enrobé est ensuite séché en compagnie d'autres ingrédients puis ramené à une taille particulaire, de manière à produire un principe actif à libération modifiée. Enfin, une fois incorporées dans un enrobage de gomme à mâcher, les particules se diffusent dans la bouche pour masquer l'amertume ou tout autre goût désagréable, tout en étant rapidement ingérées.

Claims

47



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 maltodextrin, gum arabic, 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.




48



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.
12. 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.



49



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
pseudoephedrine.
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;



50



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.

Description

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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.


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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 agents) would allow for the use of the active agentls) 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 agents) from the gum matrix.
Other methods contemplated are method of controlling release of
active agents) 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 agents) 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 1991-112450 and JP
1991-251533, disclose the use of caffeine in chewing gum to reduce
drowsiness.


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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 agents) are physically modified. Such bulk
sweeteners are sucrose, dextrose, fructose and maltodextrins, as well as
sugar alcohols such as sorbitol, mannitol, xylitol, maltitof, 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


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4
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. maltodextrin or other bulk sweeteners, as well as sugar
alcohols such as sorbitof, mannitol, xylitol. maftitol, lactitol, hydrogenated
isomaltulose and hydrogenated starch hydrolyzates.
Prior to encapsulation, active agents such as caffeine may be
combined with high-intensity sweeteners, including but not limited to
thaumatin, 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


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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
5 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 '! .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


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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:
Chewing Time % Caffeine Release


0 min --


min 56


min 73


min 88


40 min 97


5
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.
10 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
15 mouth, wilt 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
20 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,


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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 andlor metabolized. The
therapeutic effect may be one which decreases the growth of a xenobiotic or
other gut flora or fauna, afters 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. decongestants. anesthetics,


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antitussives. diuretics, anti-inflammatories, antibiotics. antivirals,
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,
riboflavin. nicotinic acid, pyridoxine, 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), procarbazine, mechlorethamine, cyclophosphamide,
camptothecin. ifosfamide, melphalan. chlorambucil, bisulfan. nitrosurea.
dactinomycin. daunorubicin, doxorubicin, bleomycin, piicomycin, mitomycin,
etoposide (VP16), tamoxifen, taxol, transplatinum, 5-fluorouracil, vincristin,
vinblastin and methotrexate or any analog or derivative variant thereof.
Antimicrobial agents that may be used include but are not limited to
naficillin, oxaciflin, vancomycin, cfindamycin, erythromycin, trimethoprim-
sulphamethoxazole, rifampin, ciprofloxacin, broad spectrum penicillin,
amoxicillin, gentamicin, ceftriazoxone, cefotaxime, chloramphenicol,
clavunate, sulbactam, probenecid, doxycycline, spectinomycin, cefixime,
penicillin G. minocycline. ~-lactamase inhibitors: mezlocillin. piperaciliin,
aztreonam. norfloxacin. trimethoprim. ceftazidime, dapsone.
Antifungal agents that may be delivered include but are not limited to
ketoconazole. fluconazole, nystatin, itraconazole, clomitrazole, and
amphotericin B. Antiviral agents that may be used include but are not limited
to acyclovir, trifluridine, idoxorudine. foscarnet, ganciclovir, zidovudine.
dideoxycytosine. dideoxyinosine, stavudine. famciclovir. didanosine,
zaicitabine, rifimantadine, and cytokines.
Antacids include cimetidine. ranitidine. nizatidine. famotidine.
omeprazole. bismuth antacids. metronidazoie antacids. tetracylcine antacids.
clarthromycin antacids. hydroxides of aluminum, magnesium. sodium
bicarbonates. calcium bicarbonate and other carbonates. silicates. and
phosphates.


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Antihistamines are represented by but are not limited to cimetidine.
ranitidine, diphenydramine, prylamine, promethazine. chlorpheniramine,
chlorcyclizine. terfenadine, carbinoxamine maleate. clemastine fumarate.
diphenhydramine hydrochloride. dimenhydrinate, prilamine maleate.
tripelennamine hydrochloride, tripelennamine citrate, chlorpheniramine
maleate. brompheniramine maieate. hydroxyzine pamoate. hydroxyzine
hydrochloride, cyciizine lactate, cyclizine hydrochloride, meclizine
hydrochloride. acrivastine, cetirizine hydrochloride, astemizole,
levocabastine
hydrochloride, and loratadine.
Decongestants and antitussives include agents such as
dextromethorphan. levopropoxyphene napsylate, noscapine, carbetapentane,
caramiphen. chlophedianol. pseudoephedrine hydrochloride,
diphenhydramine, glaucine, pholcodine, and benzonatate.
Anesthetics include etomidate. ketamine, propofol, and benodiazapines
(e.g., chlordiazepoxide, diazepame. clorezepate, halazepam, flurazepam,
quazepam, estazolam, triazolam, alprozolm, midazolam, temazepam,
oxazepam, lorazepam), benzocaine, dyclonine, bupivacaine, etidocaine,
lidocaine. mepivacaine, promoxine. prilocaine, procaine, proparcaine,
ropivacaine, tetracaine. Other useful agents may include amobartital.
aprobarbital, butabarbital. butalbital mephobarbital. methohexital,
pentobarbital. phenobarbital. secobarbital, thiopental, paral. chloral
hydrate,
ethchlorvynol, clutethimide. methprylon, ethinamate, and meprobamate.
Analgesics. include opioids such as morphine, mepidine, dentanyl,
sufentranil, alfentanil, aspirin. acetaminophen. ibuprofen, indomethacine.
naproxen, atrin, isocome, midrin, axotal, firinal. 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, tripamide.
bendroflumethiazide. benzthiazide. chlorothiazide. hydrochlorothiazide.
hydroflumethiazide. methyclothiazide. polythiazide. trichlormethiazide.


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indapamide. metolazone. quinethazone. amiloride. triamterene.
sprionolactone. canrenone. and potassium canrenoate.
Anti-inflammatories include but are not limited to salicylic acid
derivatives (e.g. aspirin) paraminophenol derivative (e.g. acetaminophen)
5 indole and indene acetic acids (indomethacin, 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).
10 Psychotherapeutic agents include thorazine, serentil. mellaril, miilazine,
tindal. permitii. prolixin. trilafon, stelazine, suprazine. taractan. navan,
clozaril,
haldol. halperon. loxitane. moban, orap, risperdal, alprazoiam.
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, wellbutrin, serzone, desyrel, nardii, parnate,
eldepryl.
Cardiovascular agents include but are not limited to nitroglycerin,
isosorbide dinitrate, sodium nitroprisside, captopril, enalapril. enalapritat,
quinapril. lisinoprif, ramipril, losartan, amrinone, lirinone, vesnerinone,
hydralazine. nicorandil, prozasin, doxazosin. 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 alias 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,


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famotidine. dramamine, omeprazole, dyclonine. chlorpheniramine maleate,
pseudoephedrine 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
formulations) 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-oligosaccharides, glucosamine, grapeseed extract. guarana, inulin,
phytosterols, phytochemicals. isoflavones. lecithin. lycopene. oligofructose,
polyphenoi and psyllium as well as weight loss agents such as chromium
picolinate and phenylpropionylamine.


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12
Preferably, the active agents or medicaments are contained in the
chewing gum formuiation at levels of approximately 50 micrograms to 500
milligrams. The specific levels will depend on the active ingredient. For
example, if chromium picofinate 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


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13
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, acesuffame 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


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14
acacia or maltodextrin can also encapsulate active agents) 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.


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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
5 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
10 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/aggiomerated/caffeine or other active agent
product that could be used in chewing gum to give a delayed release of the
15 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


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16
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 encapsulationlentrapment 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


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17
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 coatinglpanning 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
pelletslballs can then be sugar coated or panned by conventional panning
techniques to make a unique sugar coated pellet gum. Treated active
agents) can be easily dispersed in a sugar solution prepared for sugar
panning. Preferably, treated active agents) 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 arabic. gum talha. maltodextrins, 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


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18
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


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19
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 saccharide-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,
maltitoi 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.


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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
5 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
10 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
15 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.
20 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


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21
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 acesuffame-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 arabic, gum talha (another type of
acacia), alginate, cellulosics, 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.


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22
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 polyol 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


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23
the wet syrup coating in a temperature range of from about 70° to about
115°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 polyol 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.


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In a preferred embodiment of this invention, a treated active agent such
as caffeine is preblended with a gum arabic 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 arabic 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.

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TABLE 1
(WEIGHT PERCENT)
EX.1 EX.2 EX.3 EX.4 EX.S EX.6


SUGAR 52.0 49.0 48.0 44.0 41.0 39.0


GUM BASE 26.0 30.0 35.0 26.0 30.0 35.0


CORN SYRUP 20.0 19.0 15.0 18.0 17.0 14.0


GLYCERIN 1.0 1.0 1.0 1.0 1.0 1.0


PEPPERMINT 1.0 1.0 1.0 1.0 1.0 10


FLAVOR


DEXTROSE - - - 10.0 10.0 10.0


MONOHYDRATE
Encapsulated caffeine can then be used in the coating formula on the
5 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 95.1 94.4 93.1 94.9 94.1 92.6


GUM TALHA 2.0 3.0 4.0 2.0 3.0 4.0


TITANIUM 0.5 1.0 1.0 -- -- --


DIOXIDE


CALC I U -- -- -- 0.5 1.0 2.0
M


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 2.0 1.0 1.0 2.0 1.0 1.0


ENCAPSULATED
CAFFEINE

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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.

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TABLE 3
(DRY WEIGHT PERCENT)
EX. EX.18 EX.19 EX.20 EX.21 EX.22
17


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


G U M TAL -- -- -- -- 4.0 4.0
HA


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
CAFFEI NE
*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 taiha powder is dry charged after a gum taiha
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


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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.Oa~ 10.Oa~


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
SWEETENER
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 aiitame, 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 erythritol. 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:


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TABLE 5
(DRY WEIGHT PERCENT)
EX.30 EX.31 EX.32 EX.33 EX.34 EX.35


XYLITOL 93.8 91.4 89.7 89.1 88.9 87.8


GUM TALHA 4.0 6.0 7.0 8.5 8.5 10.0


FLAVOR 0.5 0.5 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 xylitol solution
** Calcium carbonate used in place of titanium dioxide
The above formulas are used to coat pellets by applying a xylitollgum
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 xylitoi 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, erythritol coating also requires a binder, film former, and
hardener in the coating to make an acceptable product. The following
formulations can be made:


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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* - - -


ACT1VE 1.0 1.0 1.0 1.0 1.0 1.0


ENCAPSULATED
CAFFEINE
* Lake color dispersed in erythritol solution
5
The above formulas are used to coat pellets by applying a
erythritol/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.
10 As in xylitol coating, some of the gum talha powder may be blended
with powder erythritol 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
15 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 goad smooth hard shell can be made. However, it may be
preferable to add a dry charge to quicken the drying process before the
20 pellets get too sticky. As above, encapsulated caffeine can be added with
the
dry charge. The following formulations may be used.


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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.
fn 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 polyol
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 polyol 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 polyof, 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.


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Some poiyols 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.
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:



Base 29.14


Sugar 47.10 '


Calcium Carbonate ~ 11.48 i


39DE, 43Be Corn Syrup 8.83 '


Glycerin 1.32


Peppermint flavor 1.32


Encapsulated high
intensity sweeteners 0.81


100.0


Comparative Example 48
The following formulas were used to prepare coating syrups for this
example:


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Syrup 1 j Syrup 2


Sugar 4885 grams ~ 3500 grams


Water j 2177 grams 1500 grams


Modified Starch ~ 206 grams ~ ---


Titanium Dioxide i 101 grams ---


Caffeine ~ 131 grams ~ ---


Total 7500 grams 5000 grams


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:
Syrup 3 Syrup 4


Sugar 5015 grams 3500 grams


~ Water 2178 grams 1500 grams


~ Modified Starch 206 grams ---


Titanium Dioxide 101 grams ---



Total ~ 7500 grams 5000 grams


Encapsulated Caffeine 240 grams


The encapsulated caffeine used in Syrup 3 was made by fluid bed
coating caffeine with an alcoholic/Zein mixture to give an 80% active
caffeine120% Zein. This material was blended with a 40% solution of gum


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arabic and some of Syrup 3 at a ratio of 60 parts encapsulated caffeine to 100
parts gum arabic 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

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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 -- --


D10XIDE


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
5 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
10 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
15 gives these types of formulas.

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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 andlor 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
75 the coating immediately after being preblended.
Gum talha is especially useful in sugarless coatings with xylitol,
sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol. 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:


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TABLE 10
(DRY WEIGHT PERCENT)
EX.66 EX.67 EX.68 EX.69 EX.70 EX.71


XYLITOL 91.8 89.4 87.7 87.1 84.9 83.8


GUM TALHA 4.0 6.0 7.0 8.5 8.5 10.0


FLAVOR 0.5 0.5 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


W~( 0.1 0.1 0.1 0.1 0.1 0.1


COLOR* - - 1.4 - - -


ACTIVE 3.0 3.0 3.0 3.0 5.0 5.0


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.


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TABLE 11
(DRY WEIGHT PERCENT)
EX.72 EX.73 EX.74 EX.75 EX.76 EX.77


SORBITOL 91.8 88.9 84.1 83.8 73.1 66.5


SORBITOL 2.0 3.0 5.0 10.0 18.0 23.0


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 3.0 3.0 3.0 3.0 5.0 5.0


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 polyol
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 polyol 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 polyol, 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.


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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 alcohollshellaclcaffeine
solution at 10% solids.
Example C - A 70% Zein, 30% active caffeine powder mixture is
obtained by spray drying an alcohoI/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 alcohollshellac solution at 30%
solids.
Example E - A 20% Zein, 80% active caffeine powder mixture is
obtained by fluid-bed coating caffeine with an alcohoIIZein 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.


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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.
5 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 11.6-12.0) 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=11.6-
10 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
and Zein.
15 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
20 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
25 aqueous solution of HPMC at 10% solids.
Example P - A 50% maftodextrin, 50% active caffeine powder mixture
is obtained by spray drying a hot aqueous solution of caffeine and
maltodextrin at 30% solids.
Example Q - A 40% gum arabic, 60% active caffeine powder mixture is
30 obtained by fluid-bed coating caffeine with an aqueous solution of gum
arabic
at 30% solids.


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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% maltodextrin, 85% active caffeine powder mixture
is obtained by agglomerating a blend of caffeine and maltodextrin, then
adding water, drying and grinding.
Multiple step agglomerationlencapsulation 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:


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Example AA - Caffeine is spray dried with maltodextrin at 30% solids to
prepare a powder. This powder is then agglomerated with a
hydroxypropyimethyl cellulose (HPMC) in a ratio of 85/15 powderlHPMC,
wetted with water and dried. After grinding the resulting powder will contain
about 68% active caffeine, 17% maltodextrin 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%
Zein.
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.


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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 411 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


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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
20% Zein.
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% gfycyrrhizin, 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 gluconate at a ratio of 16/41411 are blended together as a powder


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and extruded. The fibers are ground and gives a product containing 64%
PVAC, 16% caffeine, 16% sodium gluconate, and 4% aspartame.
Sodium gluconate is a bitterness inhibitor that can be mixed with
caffeine before being encapsulated or entrapped. This bitterness inhibitor,
5 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 maltodextrin is mixed with
a 40% hot solution of sodium gluconate. Two liters of this mixture is combined
10 with 100 grams of caffeine, dispersed and spray dried. A final product
containing 50% maltodextrin, 33% sodium gluconate and 17% caffeine is
obtained.
Example W - A 2400 ml quantity of a 25% hot aqueous solution of
maltodextrin is mixed with 50 grams of aspartame to form a suspension. To
15 this is added a hot aqueous solution of 400 grams of sodium gluconate, 200
grams of caffeine, 1200 grams of hot water. This mixture is spray dried to
obtain a powder containing 48% maltodextrin, 32% sodium gluconate, 16%
caffeine and 4% aspartame.
Example WIN - To a 2400 gram quantity of a 25% hot solution of
20 maltodextrin, 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 gluconate, 200 grams of caffeine and 1200 grams of hot
water. This mixture is spray dried to obtain a powder containing 41
maltodextrin, 28% sodium gluconate, 14% caffeine, 14% citric acid and 3%
25 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
30 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


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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.