Chewing gum can also offer an advantage for localized delivery of drug in the mouth and it is now being evaluated for these uses⁷.Chewing gum is pleasure that almost everyone enjoys⁸. Chewing gums are mobile drug delivery system. The water content of chewing gum is very low and requires no preservatives⁴.

MEDICATED CHEWING GUM

Medicated chewing gum (MCG) is containing masticatory gum base with pharmacologically active ingredients and intended to use for local treatment of mouth disease or systemic absorption through oral mucosa. Medicated chewing gum is considered as vehicle or drug delivery system to administer active principle and nutrition that can improve health and creates additional patient benefits that will add new competitive advantage for a drug and thus increase revenue. Oral route is most preferred route amongst the patient and clinicians due to various advantages it offers⁹.

Medicated chewing gum is solid, single dose preparation with a base consisting mainly of gum that is intended to be chewed but not swallowed. They contain one or more active substance which are released by chewing and are intended to be used for local treatment of mouth disease or systemic delivery after absorption through the buccal mucosa¹⁰. A drug released from medicated chewing gum has the potential of being absorbed through the epithelium of the oral cavity due to the rich vascularity of the mucosa. The drugs thereby gains direct access to the systemic circulation via the Jugular vein and avoid drug transports and first pass metabolism in the gastrointestinal tract and in the liver, thus, the bioavailability may increase. In addition some of the drug released from chewing gum may be swallowed and enter the stomach, dissolved in saliva thereby becoming easily available for absorption via GI¹¹. The first patent for the production of chewing gum was filed in 1869 and was issued to Mr. W. F. Semple in Ohio under U.S. Patent No. 98,304. A Medicated chewing gum containing Acetyl Salycilic acid was commercially introduced in 1925¹².

ADVANTAGE OF MEDICATED CHEWING GUM

Medicated chewing gum offer a wide range of advantages. They are-

· Does not require water to swallow. Hence can be taken anywhere¹³.

· Advantageous for patient having difficulty in swallowing⁴.

· Excellent for acute medication²⁹.

· Highly acceptable by Children²⁹.

· Avoid first pass metabolism and thus increase the bioavailability of drug¹³.

· Ability to retain in Oral cavity for long period for prolonged drug delivery¹⁴.

· Fast onset time for a systemic effect if the drug is readily absorbed across oral mucosa¹⁴.

· Ability to deliver drugs to the GIT and reduce irritation to the stomach owing to the drug already being dissolved or suspended in saliva before it reaches the stomach¹⁴.

· Easy to incorporate drug and manufacture¹⁴.

· Gum does not reach the stomach. Hence GIT suffers less from the effect of excipients².

· Stomach does not suffer from direct contact with high concentration of active principles, thus reducing the risk of intolerance of gastric mucosa¹².

· Stimulate flow of saliva in mouth¹³.

· Fraction of product reaching the stomach is conveyed by saliva delivered continuously and regularly. Duration of action is increased².

DISADVANTAGE OF MEDICATED CHEWING GUM

· Risk of over dosage with MCG compared with chewable tablet or lozenges that can be consumed in a considerable number and within much shorter period of time¹¹.

· Sorbital present in medicated chewing gum formulation may cause flatulence, diarrhea¹⁵.

· Chewing gum have been shown to adhere to different degree of to enamel denature and fillers¹⁶.

· Prolong chewing on gum may result in pain in facial muscle and earache in children¹⁷.

· Additives in gum like flavoring agent cinnamon can cause ulcers in oral cavity and Liquorice cause hypertension¹⁸.

ORAL MUCOSAL DRUG DELIVERY²

The oral cavity has been investigated as a site for drug delivery for a long period of time. About 60% of total dosage forms are administered by oral route. Solid dosage forms are popular because of ease of administration. Oral route of drug administration have wide acceptance due to ease of ingestion, pain, avoidance, versatility and most importantly patient compliance. Although administration through oral route has disadvantage such as hepatic first pass metabolism and enzymatic degradation with in gastro intestinal tract which prohibits administration on certain class of drug.

The two sites for oral mucosal delivery of drugs are¹⁴:-

a.) Sublingual route: The drug is placed under the tongue and allowed to dissolve.

b.) Buccal route: The medicament is placed between the cheek and the gum.

The barrier to drug absorption from this route is the epithelium of oral mucosa. Passive diffusion is the major mechanism for absorption of most drugs; nutrients may be absorbed by carrier medicated processes.

Some of the advantages of this route are:

1.) Rapid absorption and higher blood levels due to high vascularisation of the region and therefore particularly useful for administration of anti-anginal drugs.

2.) No first pass hepatic metabolism.

3.) No degradation of drugs such as that encountered in the GIT.

4.) Presence of saliva facilitates both drug dissolution and its subsequent permeation by keeping the oral mucosa.

The buccal or sublingual route appears ideal for lipid soluble drugs that are metabolized in the gastro intestinal tract or liver during absorption because the blood supply draining the buccal cavity empties directly into the systemic circulation and bypass the liver. The pH of saliva is usually about 6. Increasing the pH of fluids in the buccal cavity promote the absorption of weak bases but reduces the absorption of weak acids. A higher degree of lipid solubility may be required for good absorption from the buccal cavity than from the gastrointestinal tract. Drug released from medicated chewing gum which is not absorbed though the oral cavity membranes, will be swallowed and reach the stomach in a diluted or much dispersed form, thus being very easily available with a consequent fast of action¹⁹.

FORMULATION:

A typical formulation for chewing gum: (formula for medicated chewing gum)⁷

Sr. No.	COMPONENT	CONCENTRATION (%W/W)
1.	Drug	0-40
2.	Gum base	20-45
3.	Sweeteners	30-60
4.	Softeners	0-10
5.	Flavors	1-5
6.	Colors	0-1

Chewing gum consists basically of a neutral and tasteless gum base and several non masticatory ingredients such as fillers, softeners, sweetening agent texture regulating agent²⁰. In addition to above ingredient various additives are also used to improve properties of chewing gum, like plasticizer, elastomer, lipid(soya oil), emulsifiers(lecithin), softeners and fillers and texture agent(talc), coating and binding agent, film former, coloring agent etc. Corn syrup keeps the gum flexible and fresh²¹.

COMPONENT OF MEDICATED CHEWING GUM²²

Chewing gum is a mixture of natural and synthetic gum and resins, sweetened with sugar, corn syrup, artificial sweeteners and may also contain coloring agent and flavor. The basic raw material for all chewing gum is natural gum Chicle, obtained from the sapodilla tree¹¹.

Typically chewing gum comprises two parts:-

1.) Water insoluble chewable gum base portion

2.) Water soluble bulk portion

Water insoluble gum base generally comprises- Elastomer, resins, fats and oils and inorganic fillers.

1.) Elastomer:- Elastomer provides elasticity and controls gummy texture.

Natural elastomer: Natural rubber like latex or Natural gum such as Jetulog, Lechi Caspi, Perillo, chicle.

Synthetic rubber: Butadiene, Styrene copolymers, Polyisobutylene, Polyethylene mixture, Polyvinyl alcohol etc.

2.) Plasticizer:- These are softners and are used to regulate cohesiveness of product. It is incorporated to obtain variety of desirable texture and desirable consistency.

Natural Plasticizer: Natural rosin ester like Glycerol like Glycerol ester or partially hydrogenated rosin, Glycerol esters of polymerized esters, Glycerol ester of partially Dimerized rosin and Pentaerythretol ester of rosin.

Synthetic Plasticizer: Terpene resin derived from α- pinene and/or d-limonene.

3.) Fillers or Texturizers: Provide texture, improve chew ability, provide reasonable size of the gum lump with low dose drug.

Commonly used fillers are: Magnesium and calcium carbonate, Ground limestone, Magnesium and Aluminium silicate, Clay, Alumina, Talc, Titanium oxide and Mono/di/tri Calcium phosphate.

Water soluble portion contains²²:-

Bulk sweeteners, High intensity sweeteners, Flavoring agent, Softners, Emulsifiers, Colors and Antioxidants.

1.) Softners and Emulsifiers: These are added to the chewing gum in order to optimize the chewability and mouth feel of gum.

Softners include: Glycerin, Lecithin, Tallow, Hydrogenated tallow, Mono/di/tri glycerides, Fatty acid like stearic acid, palmitic acid, oleic acid and linoleic acid.

2.) Colorants and Whiteners: It may include FDandC type dyes and lakes, Fruit and vegetable extracts, Titanium oxide.

3.) Sweeteners: These are of two type:

a.) Aqueous sweeteners: It can be used as softners to blend the ingredients and retain moisture. These include: Sorbitol, Hydrogenated starch, hydrolysates and corn syrup. Corn syrup keeps gum Fresh and flexible.

b.) Bulk sweeteners: It include sugar and sugarless component

Sugar component: include saccharides like Sucrose, Dextrose, Maltose, Dextrin, Fructose, Galactose, Corn syrup.

Sugarless components: include sugar alcohol such as Sorbitol, Manitol, Xylitol, Hydrogenated starch hydrolysates.

High intensity artificial sweeteners can also be include to provide longer lasting sweeteners and flavor perception, eg. Sucralose, Aspartame, Salts of acesulfame, Altitame, Saccharin, Glycerrhizin, dihydrochalcones.

4.) Bulking agent: These are used when low calorie gum is desired. Example of low calorie bulking agent includes Polydextrose, Oligo-fructose, Insulin, Fructo-oligosaccharides, Guar gum hydrolysates and Indigestible dextrin.

5.) Flavoring agent: A variety of flavoring agent are used to improve flavor in chewing gum includes Essential oil such as Citrus oil, Fruit essences, Clove oil and oil of Wintergreen. Artificial Flavoring agent can also be used.

6.) Active component: In medicated chewing gum active pharmacological agent may be present in core or coat or in both. The proportion of which may vary from 0-40% of final gum weight. A small, unionized, lipophilliic and enzymatically stable active agent is likely to be absorbed more rapidly. A saliva soluble ingredient will be completely released within 10-15 minutes of chewing whereas lipid soluble ingredient will dissolve in the gum base and thereafter be slowly and completely absorbed.

Medicated chewing gum consists of masticatory gum core that may be coated. The core is composed of an aqueous insoluble gum base which can be mixed with sweeteners and flavors. The coating can be applied as a film of polymers, waxes, sweeteners, flavors and colors or a thick layer of sugar or sugar alcohol.

METHOD OF MCG PREPARATION

Different method can be employed for the manufacturing of chewing gum, however, these can be broadly classified into three main classes namely:-

1.) Conventional / Traditional method (Melting)

2.) Cooling, Grinding and Tableting method

3.) Direct compression method

Conventional / Traditional method²³:-

Components of gum base are softened or melted and placed in a kettle mixer to which sweeteners, syrups, active ingredients and other excipients are added at a definite time. The gum is then sent through a series of rollers that form into a thin, wide ribbon. During this process, a light coating of finely powdered sugar or sugar substitutes is added to keep the gum away from sticking and to enhance the flavor. In a carefully controlled room, the gum is cooled for up to 48 hours. This allows the gum to set properly. Finally the gum is cut to the desired size and cooled at a carefully controlled temperature and humidity.

However, the conventional methods have several limitations:

1.) Elevated temperature used in melting restricts the use of this method for thermolabile drugs.

2.) Melting and mixing of highly viscous gum mass makes controlling of accuracy and uniformity of drug dose difficult.

3.) Lack of precise form, shape or weight of dosage form.

4.) Technology not so easily adaptable to incorporate the stringent manufacturing condition required for production of pharmaceutical products.

5.) Such a chewing composition is difficult to form into chewing gum tablet because of their moisture content (2-8%). If attempted to grind and tablet such a composition would jam the grinding machine, stick to blades, screens adhere to punches and would be difficult to compress.

Cooling, Grinding and Tabletting method^{23, 24}:

This method has been developed with an attempt to lower the moisture content and alleviate the problem faced in conventional method.

Cooling and Grinding

The CG composition (base) is cooled to a temperature at which the composition is sufficiently brittle and would remain brittle during the subsequent grinding step without adhesion to the grinding apparatus. The temperature required for cooling is determined in part by the composition of the CG and is easily determined empirically by observing the properties of the cooled chewing gum composition. Generally the temperatures of the refrigerated mixture are around -15ºC or lower. Amongst the various coolants like liquid nitrogen, hydrocarbon slush use of solid carbon dioxide is preferred as it can give temperatures as low as -78.5ºC, it sublimes readily on warming the mixture, is not absorbed by the chewing gum composition, does not interact adversely with the processing apparatus and does not leave behind any residue which may be undesirable or potentially hazardous.

The refrigerated composition is then crushed or ground to obtain minute fragments of finely ground pieces of the composition. Alternatively, the steps of cooling the chewing gum composition can be combined into a single step. As an example, cooling the grinding apparatus itself which can be done by contacting the grinding apparatus with a coolant or by placing the grinding apparatus in a cooling jacket of liquid nitrogen or other cold liquid. For more efficient cooling, the chewing gum composition can be pre cooled prior to cooling to the refrigeration temperature.

Sometimes a mixture of chewing gum composition, solid carbon dioxide and precipitated silica is ground in a mill grinder in a first grinding step. Additional solid carbon dioxide and silica are added to the ground composition, and the composition is further ground in a second grinding step. This two step grinding process advantageously keeps the chewing gum composition at a very low temperature. The presence of solid carbon dioxide also serves to enhance the efficiency of the grinding process. The same process can be made multiple by adding incorporating additional carbon dioxide and/or precipitated silica at each step. Certain additives can be added to the chewing gum composition to facilitate cooling, grinding and to achieve desired properties of chewing gum. These include use of anti-caking agent and grinding agent. Once the coolant has been removed from the powder, the powder can be mixed with other ingredient such as binders, lubricants, coating agents and sweeteners etc. all of which are compatible with the component of chewing gum base in a suitable blender such as sigma mill or a high shear mixer.

Use of anti-caking agent

An anti-caking agent such as precipitated silicon dioxide can be mixed with chewing gum Composition and solid carbon dioxide prior to grinding. This helps to prevent agglomeration of the subsequently ground chewing gum particles.

Use of grinding agent

To prevent the gum from sticking to the grinding apparatus, 2-8% by weight of grinding aid such as alkaline metal phosphate, an alkaline earth metal phosphate or malto dextrin can be incorporated. However practical use of these substances is limited because these substances are highly alkaline and hence would be incompatible with acidic ionisable therapeutic agents. They also tend to remain in the composition and final chewing gum tablet and thus may be problematic for therapeutic and safety point of view.

Tabletting

Once the coolant has been removed from the powder, the powder can be mixed with other ingredients such as binders, lubricants, coating agents, sweeteners etc, all of which are compatible with the components of the chewing gum base in a suitable blender such as sigma mill or a high shear mixer. Alternatively a Fluidized Bed Reactor (FBR) can be used. The use of FBR is advantageous as it partially rebuilds the powder into granules, as well as coats the powder particles or granules with a coating agent thereby minimizing undesirable particle agglomeration. The granules so obtained can be mixed with anti-adherents like talc. The mixture can be blended in a V type blender, screened and staged for compression. Compression can be carried out by any conventional process like punching.

Direct compression method²⁵

Using directly compressible chewing gum excipients:

The manufacturing process can be accelerated if a directly compressible chewing gum excipient is available. The limitations of melting and freezing can be overcome by the use of these. PHARMAGUM®, is one such compactable gum system developed by SPI Pharma. Pharmagum is a mixture of polyol(s) and or sugars with a chewing gum base. It is available as directly compressible powder, free flowing powder which can be compacted into a gum tablet using conventional tablet press thus enabling rapid and low cost development of a gum delivery system. It is manufactured under CGMP conditions and complies with Food Chemicals Codex specifications as well as with FDA, so they can be considered as "Generally regarded as safe" (GRAS).

Pharmagum® is available in three forms namely S, M and C. Pharmagum® M has 50% greater gum base compared to Pharmagum®S. Pharmagum®S consists primarily of gum base and sorbitol. Pharmagum®M contains gumbase, mannitol and Isomalt. Release of nicotine from directly compressible nicotine gum formulations and from Nicorette® prepared by conventional method have shown that use of Pharmagum in formulation showed a faster release rate. Formulations made with Pharmagum® M and S are similar to tablet in appearance. Gums formed using compressible formulation are 10 times harder and crumble when pressure is applied resulting in faster release than conventional methods. Use of Pharmagum S, M and C enables formulators to utilize a gum delivery system quickly and more cost effectively than by traditional methods.

CHARECTERIZATION OF MEDICATED CHEWING GUM²⁶:

1.) Physical evaluation of MCG :

All Medicated Chewing Gum formulations were visually inspected; various physical properties of gum base were studied on basis of their solubility studies, relative humidity and color and moisture absorption.

Following parameters were studied:

a.) Physical evaluation of MCG: All formulation prepared were physically evaluated for following parameters, appearance, color, stickiness, hardness, weight variation, texture analysis.

b.) Hardness / Plasticity: Due to absence of any reported method, it was decided to use the Monsanto type hardness tester for determination of hardness of all MCG formulation. Texture analysis was used for determining strength and degree of deformation. Values obtained indicate flexibility of sample.

c.) Weight variation: Weight of 10 chewing gum was taken in one batch and then average weight is calculated from that standard deviation is calculated.

d.) Stickiness: Texture analyzer from stable micro system model TA.XT-EXPRESS was used for determining stickiness and degree of deformation. Values obtained indicate uniformity of sample.

2.) Chew out study: Chew out study protocol was formulated based on input from Fertin Pharma Pvt Ltd Denmark, one of the world largest manufacturers of medicated chewing gum. Following scoring pattern was developed from specific input from Fertin Pharma Pvt Ltd, Denmark. Initial phase of chew out study include various parameter like texture, elasticity, smoothness, crankiness, softness, cheesiness, sweetness, cooling effect, hardness, juiciness and lubricating feel.

IN-VITRO DRUG RELEASE TESTING APPARATUS:-

Number of apparatus for studying in-vitro drug release from medicated chewing gum has been developed. An apparatus for in-vitro drug release testing of medicated chewing gum has been developed by Kvist C et al. they have studied the effect chewing surfaces, twisting movement of surfaces and temperature of test medium on release rate of drug from MCG. Another novel dissolution apparatus has been developed for MCG by Rider JN et al. the apparatus consist of conical Teflon base and a rotating, ribbed Teflon plunger suspended in a dissolution vessel. The rotation speed, plunger frequency, medium volume, medium type, medium sampling location, number of plunger ribs and number of gum pieces were studied by them²⁷.

APPARATUS 1:- the chewing gum apparatus for medicated chewing gum was adopted by Ph. Eur. in 2000²⁸. Figure 1 shows the construction of the apparatus. The chewing apparatus comprises a chewing chamber, two horizontal pistons, and a third vertical piston (tongue). The vertical piston operates alternatively with the two horizontal pistons and makes sure the gum stays in the right place between chews. If necessary, it is feasible to construct the machine so that at the end of the chew the horizontal pistons rotate around their own axes in opposite direction to each other to obtain maximum chewing. The working procedure of this apparatus is described in Ph. Eur. Several studies have been carried out using the Ph. Eur. Apparatus and the results indicate the methodology is rugged and reproducible²⁹.

Figure 1: Apparatus for the determination of drug release from medicated chewing gum²⁸

Figure 2: apparatus for in-vitro dissolution of chewing gum³[adopted fromGavaskar B. et al]

A. Horizontal piston; B. Guide; C. Chewing chamber; D. Funnel; E. Vertical piston

APPARATUS 2: Noncompendial- Wennergren

One of the noncompendial apparatus commercially available was designed by Wennergren. The schematic representation of the Wennergren chewing apparatus is shown in figure 2. The chewing procedure consist of reciprocation of the lower surface in combination with a shearing (twisting ) movement of the upper surface that provides mastication of the chewing gum and at the same time adequate agitation of the test medium. The upper jaw has a flat surface that is parallel to the central part of the lower surface. The small brim of the lower surface is angled upwards (45 degree) so that the lower surface function as a small bowl with a flat bottom. The bowl prevents the chewing from sliding during mastication. Investigations of the performance of the chewing apparatus with multiple drug products were published by Wennergren et al. the influences of different operational parameters of the chewing gum apparatus on drug release have been carefully investigated^30,31.

Figure 2: single module chewing apparatus by Wennergren (adopted from³² Gadhavi et al.)

FACTOR WHICH AFFECT RELEASE OF ACTIVE INGRADIENT³²:-

1. Contact time: The local or systemic effect dependent on time of contact of MCG in oral cavity. In clinical trial chewing time of 30 minutes was considered close to ordinary use.

2. Physicochemical properties of active ingredients: Physicochemical properties of active ingredient plays very important role in release of drug from MCG. The saliva soluble ingredients will be immediately released within few minutes whereas lipid soluble drugs are released first into the gum base and then released slowly.

3. Inter individual variability: The chewing frequency and chewing intensity which affect the drug release from MCG may vary from person to person. In-Vitro study prescribed by European Pharmacopoeia suggest 60 cycles per minute chewing rate for proper release of active ingredient.

4. Formulation factor: Composition and amount of gum base affect rate of release of active ingredient. If lipophilic fraction of gum is increased, the release rate is decreased.

APPLICATION OF MEDICATED CHEWING GUM^33-35:

Today medicated chewing gum is mostly used for the local and systemic effects. Application of MCG is following:

A) Local therapy:

1.) Dental Caries: The main target of medicated chewing gum is to prevent and cure the oral disease. It can control the release rate of active substances and provide a prolonged local effect. It also re-elevates plaque pH which lowers the intensity and frequency of dental caries. Chewing gum which contains Fluoride is used in prevention of dental caries in children and in adult with Xerostomia. Chlorhexidine chewing gum can be used to treat gingivitis, periodontitis, oral and pharyngeal infections and also used for inhibition of plague growth. Chlorhexidine chewing gum offers large flexibility in its formulation as it gives less staining of the teeth and is distributed evenly in the oral cavity. The bitter taste of chlorhexidine can be masked quite well in a chewing gum formulation^{30, 31}.

B) Systemic Therapy:

1.) Pain- Chewing gum is used in the treatment of minor pains, headache and muscular aches. Pharmagum® is available medicated chewing gum which contains Acetylsalicylic acid.

2.) Smoking cessation- Chewing gum formulation containing Nicotine, Lobeline and Silver acetate have been clinically tested as aids to smoking cessation. It is intended to help smokers break the psychological habit of smoking by reducing the nicotine withdrawal symptoms normally experienced when smoking is stopped

3.) Obesity: active substance like chromium, guaran and caffeine are proved to be efficient in treating obesity. Chromium is claimed to reduce craving for food due to an improved blood-glucose balance. Caffeine and Guaran stimulate lipolysis and have a thermogenic effect (increased energy expenditure) and reduce feeling of hunger.

4.) Stimulating activating Effect- it is a well known fact that caffeine has stimulating effect. It could, therefore, be interesting to combine it with chewing gums generally positive effect on memory. The ability of healthy volunteers to stay awake at night was tested in two different experiments.

5.) Other indication: Xerostomia, Allergy, Motion sickness, Acidity, Cold and Cough, Diabetes, Anxiety, etc. are all indications for which chewing gum is a means of drug delivery.

Optimal Properties of Drug¹¹

Physicochemical Properties of Drug	High Salivary Solubility
	pH independent Solubility
	Tasteless
Patient Related Factors	Non-toxic to oromucosa and salivary ducts
	Non-carcinogenic
	Should not cause tooth decay
	Should not cause oro-mucosa and teeth staining
	Should not affect salivary flow rate

PATENTS ON CHEWING GUM

Patents no.	Inventors	Comments
7,078,052	Ream el al. (2006)³⁶	Pharmaceutical chewing gum formulation
6,645,535	Zyck et al. (2003)²⁰	Method of making coated chewing gum products containing various Antacid
6,586,023	Song et al. (2003)³⁷	Process for controlling release of active agents from a chewing coating and product thereof
6,582,738	Gubler (2003)³⁸	Process for preparing chewing gum containing a Nutritional supplement
6,344,222	Cherukuri et al. (2002)³⁹	Medicated chewing gum delivery system for nicotine
6,322,828	Athanikar et al. (2001)²³	Process for manufacturing a pharmaceutical chewing gum
5,866,179	Testa (1999)⁴⁰	Medicated chewing gum and a process for preparation thereof
4,588,592	Elias (1986)⁴¹	Chewing gum products and composition and process for the preparation thereof
4,224,345	Tezuka et al. (1980)⁴²	Chewing gum base and a combination of a chewing gum with fatty matter
4,000,321	Mochizuki et al. (1976)²⁴	Process for the preparation of chewing gum

CONCLUSION:

Finally, It is concluded the that Chewing gum is an excellent delivery system for drugs intended for the treatment of oral diseases, e.g. fungal disease, dental caries as well as social disease such as smoking. Chewing gum is believed to manifest its position as a convenient and advantageous drug delivery system as it meets high quality standards of pharmaceutical industries, alongwith ease in administration, patient compliance and other clinical benefits. Active ingredients with extremely bitter taste and poorly water soluble drugs are not suitable, therefore requires specialized techniques to mask the taste and promote drug release respectively.

Apart from the above benefits medicated chewing gum has not yet been fully exploited due to lack of specific equipments and facilities that are required for formulation, which are rare in pharma industry. Also the therapeutic uncertainties related to delivery method-namely patients mechanical chewing action like chewing force, frequency and time, are the area of concern where result may vary. In the future chewing gums as a drug delivery system will address a bright future for a preparation with a long history.

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Received on 10.10.2012

Modified on 18.10.2012

Accepted on 30.10.2012

Research J. Science and Tech. 4(5): September –October, 2012: 220-228

Trade Mark	Active ingradients	Purpose	Commercially available
Aspergum	Aspirin	Pan relief	North America
Nicorette	Nicotine	Smoking cessation	Worldwide
Nicotinelle	Nicotine	Smoking cessation	Western Europe, Australia, New Zealand
NiQuitin CQ	Nicotine	Smoking cessation
Trawell	Dimenhydrinate	Travel illness	Italy, Switzerland
Superpep	Dimenhydrinate	Travel illness	Germany, Switzerland
Chooz	Calcium carbonate	Stomach acid neutralization	USA
Endekay Vitamin C	Vitamin C	General health	Middle East, United Kingdom
Stamil Vitamin C	Vitamin C	General health	Australia
Source Vitamin C	Vitamin C	General health	Australia
Brain	DHE and CCE	Enhanced brain activity	Japan
Stay Alert	Caffeine	Alertness	USA
Café Coffee	Caffeine	Alertness	Japan
Buzz Gum	Guarana	Alertness	United Kingdom
Go Gum	Guarana	Alertness	Australia
Chroma Slim	CR	Diet	SA
Fluorette	Fluoride	Cariostatic	USA
HEXIT	Chlorhexidine	Prevention of caries
Vitaflo CHX, Advanced plus	Chlorhexidine	Preventing Tooth decay	USA
Travel	Dimenhydrinate	Motion sickness	USA, Australia
V6	Xylitol	Prevention of formation of dental caries	United Kingdom