www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______INTERNATIONAL JOURNAL OF ADVANCES IN PHARMACY, BIOLOGY AND CHEMISTRY Review Article

An Updated Review on Medicated Gum Pramod Kumar Biswal* and Anantkumar R.K.D.F School of Pharmaceutical Sciences, Bhopal, Madhya Pradesh, India.

ABSTRACT Chewing gums are mobile systems. It is a potentially useful means of administering drugs either locally or systemically via, the oral cavity. The medicated chewing gum has through the years gained increasing acceptance as a drug delivery system. Several ingredients are now incorporated in medicated chewing gum, e.g. Fluoride for prophylaxis of dental caries, chlorhexidine as local disinfectant, nicotine for cessation, aspirin as an analgesic, and caffeine as a stay alert preparation. In addition, a large number of chewing gum intended for prevention of caries, alleviation, and vitamin/ mineral supplementation are currently available. Today improved technology and extended know how have made it possible to develop and manufacture medicated chewing gum with predefined properties. MCGs (Medicated chewing gums) are solid, single dose preparations with a base consisting mainly of gums that are intended to be chewed but not swallowed. They contain one or more active substances which are released by chewing and are intended to be used for local treatment of mouth diseases or systemic delivery after absorption through buccal mucosa. The present review article is nicely discussed advantages, disadvantages, formulation, manufacturing process, limitation of manufacturing process, factors affecting release of active substance, quality control tests for chewing gum, significance, stability study and future trends in chewing gum drug delivery system.

Keywords: Chewing , gum, medicated gum, elastomer, Novel Dissolution apparatus, dental caries.

INTRODUCTION and contains acetylsalicylic acid. Another Chewing gum is being used worldwide since ancient commercially available medicated chewing gum is times after man experienced the pleasure of chewing dimenhydrinate – containing chewing gum for a variety of substance. One thousand years ago the . However, chewing gum did not gain Mayan Indians chewed from the sapodilla acceptance as a reliable drug delivery system until tree in order to clean their teeth and freshen their 1978, when nicotine chewing gum became available. breath. Shortage of bases during World Today improved technology and extended know how War II enhanced development of the synthetic gum have made it possible to develop and manufacture bases that are used today. Chewing gum can be used medicated chewing gum with pre-defined properties. as a convenient modified release drug delivery Consequently, today chewing gum is aconvenient system. Medicated chewing gums are currently drug delivery system, which is appropriate for a wide available for pain relief, smoking cessation, travel range of active substances. Medicated chewing gum illness, and freshening of breath. In addition, a large offers advantages in comparison to conventional oral number of chewing gum intended for prevention of mucosal and oral dosage forms both for (a) local caries, xerostomia alleviation and vitamin / mineral treatment (b) systemic effect after absorption through supplementation are currently available. The first the buccal and sublingual mucosal and from the commercial chewing gum “State of Maine pure . Chewing gum can be retained gum” was marketed in 1948 in the U.S.A. The in the oral cavity for a long period and, if the drug is first patent was filed in 1869. The gum was intended readily absorbed across oral mucosa, chewing gum as dentifrices but it has never been marketed. The can provide a fast onset time for a systemic effect and first Medicated chewing gum “Aspergum” was the potential for avoidance of gastrointestinaland launched in 1928. This chewing gum is still available hepatic first – pass metabolism of susceptible drugs.

351 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______Generally, medicated chewing gum has a good 10. The active compounds absorbed at oral level stability, the medicine can be taken easily and avoid the hepatic circulation andthe directly without the prerequisite of water, and if associated metabolism. required, prompt discontinuation of medication is 11. The product is rapidly released from the possible. Physiochemical properties of the drug like gum after a short period mastication;some aqueous stability, pKa value, distribution between absorption takes place by directly through gum/ saliva, product properties like, composition, the oral mucosa depending onthe active mass, manufacturing process and the process of ingredient. Importantly not being swallowed chewing i.e. chewing time, chewingrate, affects the the gum does not reachthe . release of drugs from the medicated chewing gum. Moreover, the stomach does not suffer from Varying the formulation and manufacturing process, direct contact withhigh concentrations of chewing gum as a drug delivery system can be active principle, this reducing the risk of formulated for an extended period of time. intolerance ofthe gastric mucosa. 12. The fraction of product reaching the CHEWING GUM FOR stomach is conveyed by the saliva BUCCAL DELIVERY anddelivered continuously and regularly. Dosage forms such as , erodible/ Active substances are released frommedical chewable buccal tablets, and chewing gums allow chewing gum during chewing and are release of drugs for only a short period and thus the dissolved in saliva. The releaserate can be reproducibility of drugs absorption is comparatively carefully controlled through the formulation poor. Application of semisolid of the chewing gumallowing creates considerable technical problems in the buccal extendedexposure in the oral cavity. Active absorption. Although medicated chewing gums pose substances that areabsorbed through the difficulties in regulating the dose administered, they buccal mucosa pass via the jugular veins still have some advantages as drug delivery devices, directly into thesystemic circulation. Due to particularly in the treatment of diseases in the oral the rich vascular supply of the buccal cavity and in nicotine replacement therapy. Some mucosa,measurable concentrations of active commercially available chewing gums are Caffeine substances may be in the blood after onlya chewing gum, (Stay Alert®,) and Nicotine chewing few minutes of chewing and fast onset of gums(e.g. Nicorette ® and Nicotinell®). The action is thus likely to be permeability of nicotine across the Buccal mucosa is attained.Furthermore, bioavailability may be faster than across the skin. However, chewing gum increased, as hepatic first passmetabolism slowly generates a steady plasma level of nicotine and gastrointestinal tract degradation are rather than a sharp peak as experienced when tract degradation areavoided for buccal- smoking. Possible swallowing of considerable absorbed substances. amount of nicotine during chewing may lead to 13. Consequently, a lower dosage of substance decreased effectiveness of the chewing gum due to may be therapeutically sufficient,possibly first pass metabolism and gastrointestinal discomfort. resulting in a fewer side effects, and It is a major challenge to optimize the dose-response promote fast absorption. Activesubstances relationship of nicotine administered in a chewing released from chewing gum are dissolved in gum. saliva whenswallowed and are, therefore, readily accessible for absorption in ADVANTAGES thegastrointestinal tract. 1. Convenient – promoting higher compliance 2. Discreet- less stigmatization MANUFACTURING 3. Administration without water can be taken 1. -Gum base is an inert and anywhere insoluble nonnutritive product used as 4. Excellent for acute medication asupport for the edible and soluble of the 5. Advantageous for patients with difficulty in chewing gum (, glucose, polyoils and swallowing tablets flavors) other raw materials are generally 6. Pleasant taste grouped in the followingclasses: 7. Counteracts dry mouth: Through stimulation 2. Elastomers: including natural and synthetic of the salivary secretion thereby preventing. rubbers. The gum basecomposition may 8. Candidacies and caries. contain conventional elastomer solvents to 9. Highly acceptable by children aid in softeningthe elastomer base component. Such elastomer solvents may

352 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______compriseterpinene such as mixtures there of, may be included of alpha-pinene or beta-pinene, asantioxidants. methyl,glycerol or pentaerythritol esters of 6. Compression adjutants: Suitable resins or modified resins and gums, suchas compression adjuvant such as hydrogenated, dimerized or polymerized silicondioxide, magnesium stearate, calcium resins or mixtures. The elastomersolvents stearate and talc can be used inmedicated may be employed in amounts from 5.0% to chewing gum for ease of compression. The 75.0%, by weight of thegum base, and alkaline earth metalphosphates and alkali preferably from 45.0% to 70.0%, by weight metal phosphates prevent caking and balling of the gum base.Synthetic elastomers such of “High”i.e. 2 to 8% moisture- containing as , styrene copolymers, chewing gum compositions during polyisobutylene,isobutylene isoprene grinding.Additionally, it has been copolymers, polyethylene mixtures, and discovered that maltodextrin enhances the non-toxic vinylpolymer, such as polyvinyl grindingof “high” moisture-containing alcohol are widely used bases. The chewing gum compositions by molecularweight of the vinyl may absorbingmoisture to allow lubrication in range from 3,000 to 94,000. The amount the gum as it separates into granules. If ofgum base employed varies greatly oillubricants are used, it is preferred to be depending upon various factors such as 0.4% to 1% by weight of the thetype of base used, the consistency of the tabletedchewing gum composition. The gum desired and the othercomponents used amount of glidant present in the in the composition to make the final tabletedchewing gum composition is from chewing gum product.In general, the gum 0.5% to 5% by weight of the base willbepresent in amount from 5% to tabletedchewing gum composition. Those 94%, by weightof the final chewing gum glidants useful are selected from the composition. Preferably, the gum base is groupconsisting of alkali metal salts, talc, used inamounts from 15% to 45% and more starch, polyhydric alcohols and preferably in amounts from 15% to 35%by mixtures.Antiadherents function to prevent weight of the final chewing gum tablet granulations from sticking to the composition. facesof the punches and the die walls, but 3. : , vegetable oils, most importantly, prevent adherence glycerides. Plasticizers or softeners suchas ofchewing gum granules from adhering to lanolin, palmitic acid, oleic acid, stearic one another, a phenomenon known acid, sodium stearate, potassiumstearate, asblocking. Anti- adherents may be added to glyceryl triacetate, glyceryl lecithin, the chewing gum compositionwhile the glycerylmonostearate,propylene glycol composition is in the hoppers, or subsequent monostearate, acetylated monoglyceride, to grinding and areselected from the group glycerine, naturaland synthetic waxes, consisting of silicates, silicon dioxide, talc hydrogenated vegetable oils, polyurethane andmixtures thereof present in amount of waxes,paraffin waxes, microcrystalline 0.2% to 1% by weight of the waxes, fatty waxes, tabletedchewing gum composition and sorbitalmonostearate,propylene glycol, may preferably about 0.3 to about 0.6% by be incorporated into the gum base to obtain weight.Generally anti-adherent is a finely a variety ofdesirable textures and divided low bulk density , which consistency properties. ispreferably water insoluble. The preferred 4. Adjuvants: calcium carbonate, talc, or other anti-adherents are fumed silica andtalc. The charging agents are used.Mineral adjuvant term-fumed silica is meant to include such as calcium carbonate, magnesium pyrogenic silicas, micron sizedsilicas and carbonate, aluminumhydroxide, aluminum hydrated silicas. silicate, talc, tricalcium phosphate, 7. Sweeteners dicalcium phosphateserve as fillers and a) Water-soluble sweetening agents: textural agents. xylose, ribulose, glucose,mannose, 5. Antioxidants: An anti- oxidant such as galactose, , sucrose, maltose, invert butylatedhydroxytoluene, sugar partiallyhydrolyzed starch, butylatedhydroxyanisole, propyl gallate and dihyrochalcones, monellin, steviosides,glycyrrhizin, and sugar alcohols

353 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______such as , ,hydrogenated mass. Additional components (such starch hydrolsates. asflavors or active ingredients) then are b) Water-soluble artificial sweeteners: blended into gum base. Finally, themixture soluble saccharin salts, i.e.sodium or is cooled, pressed and cut to produce the calcium saccharin salts,cyclamate salts. final product. c) Dipeptide based sweeteners: L- aspartic 2. Alternatively, various components are acid derived sweeteners suchas Aspartame, blended in gum slurry that is Alitame, methyl esters of L-aspartyl-L coagulatedbefore pressing into the final phyenylglycerineand Laspartyl- L 2,5- product form. dihyrophenylglycine, L-aspartyl 2,5- 3. To avoid the degradation of the active dihydro-L phenylalanine – L aspartyl – L (1- agents, coldproduced chewing gum bydirect cyclohexen) alanine. compression of the ingredients has been d) Water-soluble sweeteners: derived from tried so as to retard or controlthe release rate naturally occurring watersolublesweeteners, of active agents along with the chlorinated derivatives of ordinary sugar microencapsulated activeagents. (sucrose,known as Sucralose) e) Protein based sweeteners: such as PROBLEMS ASSOCIATED WITH ABOVE thaumaoccousdanielli (ThaumatinI and II) In METHODS general an effective amount of sweetener is 1. Many pharmaceutically active agents utilized toprovide the level of sweetness possess unpleasant taste or odor thatresults desired, and this amount will vary withthe in the undesirable chewing gum products. sweetener selected and are present in Many active agents also tendto irritate the amounts from 0.0025% to mucosa and few others degrade rapidly, 90% by weight of the gum composition. making impractical toinclude them in 8. Coloring Agents: The coloring agents chewing gum. include pigments, which may 2. Another problem associated with the above beincorporated in amounts up to about 6% methods is that the gum base isheated to a by weight of the gum composition,titanium fluid mass to facilitate mixing of other dioxide may be incorporated in amounts up ingredients. Such elevatedtemperatures can to about 2%. Thecolorants may also include cause degradation of heatsensitive natural colors and dyes suitable for compounds, includingactive agents and food drugand cosmetic applications. flavors. 9. Flavoring Agents: Flavoring agents suitable 3. Further, medicated gum preparations often for use are essential oils andsynthetic flavors utilize organic solvents to dissolvethe active such as citrus oils, fruit essences, agents, it is difficult to eliminate these oil, spearmintoil, clove oil organic solvents from thefinal product and oil, and anise oil. may present certain health risks if even trace amounts remainin the final dosage forms. PROCESS FOR PREPARATION 4. Additionally use of organic solvents in Different authors have reported various processes of connection with industrial processes preparation of medicatedchewing gum, that are isbecoming increasingly unpopular due to mentioned as under: health and environmentalconsiderations (e.g. 1. Formation of a inclusion complex, which is risks attendant to exposure of personnel and dried and mixed granulated gumbase problems ineffecting proper disposal of without adding water or other solvents. The waste solvents). process is carried out atcontrolled 5. Water can also be utilized in gum temperature and humidity and the blended preparations but it is difficult to components are coldpressed to produce a eliminate,especially at the relatively low final gum product. Attempts have been temperatures that are desirable for made toincorporate pharmaceutically active productionof chewing gum. Heating the gum agents into chewing gum as means mass to eliminate water is not ofadministering the active agent to the advisable,because the gum will then become subject. Traditionally, these efforts stickier which makes handling difficult haveemployed common chewing gum andinterferes with large scale, semi-or production techniques wherein a gum base totally automated production. isheated until it becomes viscous or fluid Conventionalchewing gum compositions are

354 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______difficult to form into chewing gum accentuated. In addition thistechnique provides an tabletsbecause of their moisture content. excellent means of masking the unpleasant Traditional chewing gum organolepticcharacteristics of many active agents. compositionscontain 2% to 8% by weight of One or more well-known chewing gumexcipients can water. be added to the gum base before or after combining it 6. Generally the chewing gum will jam the with theinclusion complex. The powder containing grinding machine, sticking to blades,screens the inclusion complexes ofcyclodextrin and active and other surfaces if moisture level is not agent is mixed with the processed gum base in controlled. Traditionalmoisture levels can theabsence of water or organic solvents. The ratio cause caking and balling of the gum during between the inclusion complexand the processed gum granulationprocess thereby preventing the based can vary widely depending on the amount formation of gum granules that are ofactive agent that should be delivered. The necessaryfor . Alternatively, if medicament is added to the gumgranules along with moisture content is greater than 2% by the compression aid, pharmaceutical drugs or other weight,various other problems can occur, activeagents are added in a number of formsincluding e.g. adherence to the punch encapsulated, but they arepreferably added in a dry press,compaction in the punch press hopper, state. Active agents may themselves be granulatedand poor low in the feeder section anddifficulties added in this form to the tableted chewing gum with compressibility. Thus the problems of composition. Liquidwater-soluble drugs can be added realizing a medicatedchewing gum produced to a of modified malt dextrin andspray dried. by direct compression with immediate or , oil soluble drugs and active agents can be rapid releaseof the active agent and efficient blended withthe compression aid components prior to masking of unpleasant mixing with the gum granules, theliquid drug or organolepticcharacteristics of active agents active agent should not exceed more than 30% by remain unsolved. In view of the deficiencies weight. Theadvantage of the tableted gum ofthe prior methods of producing medicated composition as a means for dispensing chewing gum containing activeagents a drugsmedicaments and other active agents is that the process has been reported that overcomes component is trapped betweengranules and not these various shortcomingsand provide a within the gum composition. Hence, it is readily novel process for producing medicated bioavailableand nearly completely released upon chewing gum containinginclusion chewing of the gum. complexes of cyclodextrins and active agents. This process avoidsthe use of STABILITY organic solvents and water and is especially The stability of chewing gum is comparable to that of adapted for use withheat sensitive active most other soliddelivery systems. Chewing gum agents. Further, it avoids the heated gum normally contains little water (2.5%). If thewater base and slurriestoo. The novel method that content is very critical for the stability of drug, the has been patented includes cooling the gum chewing gum can bemanufactured without water basegrinding it into granules, which are then (less 0.2%). This will however, often make dry-mixed with optional excipients inthe theproduct hygroscopic and will affect the texture. absence of water and solvents at controlled The low water content alsoinhibits microbial growth temperature and humidity,cold- pressing the in the chewing gum during storage. Furthermore, mixed gum and components into the final theproduct can be protected against oxidation by a product. Thehydro-soluble and lipid soluble sealed coat and by anappropriate packing. For every active agent are encapsulated in temperature-labile component, e.g. enzymes,the cyclodextrinsand are liberated in the mouth process temperature of 50-600 C during mixing may by saliva amylases. By inclusion create a stabilityproblem. It is however possible to incyclodextrins, the active agents are operate the process at a lower temperatureto avoid stabilized and are made more soluble. this issue. Thewell-developed technology used for generating the inclusion complexes QUALITY CONTROL issimpler and advantageous when compared As per specifications given in European to that of micro encapsulation. Pharmacopoeia. Furthermore, through the use of the inclusion 1. Test for Uniformity of Content: Unless complexes, the bioavailability ofthe otherwise prescribed or justified cyclodextrinencapsulated active agents is andauthorized medicated chewing gum with

355 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______content of 2 mg or less than 2 percentof the complex bound to acation exchange resin leading to a total mass of gum comply with test. prolonged release. This ion exchange principlecould 2. Uniformity of mass: Uncoated medicated of course, also be used for other ionic substances. It chewing gum and unless otherwisejustified is also possible to granulatethe active substance with and authorized coated medicated chewing hydrophilic components, melted lipids, or to mix the gum comply with the testfor uniformity of activesubstance with a melted polymer. mass of single- dose preparations. 6. The active substance: The release rate of an 3. Drug release from medicated chewing active substance depends on thesolubility of the gum: It has been reportedcommercially that active substance in water and saliva. Highly the drug release from medicated chewing hydrophilic substancewill be almost completely gum as per thespecification given in released within 10 to 15 minutes. Substances European Pharmacopoeia and is determined withsolubility in water or less than 0.1 – lg/100ml by applyinga mechanical kneading are lipophilic components of the gumbase and procedure to a piece of gum placed in a thereby show a slow and incomplete release. small chewingchamber containing a known Active substances may befound in the form of volume of buffer solution. salts or compounds with different , e.g. pro-drugs,thus the compound offering the best FACTORS AFFECTING RELEASE properties for achieving optimal release may The release rate of an active substance is determined beselected. Chlorhexidine can serve as an not only by the formulation ofthe chewing gum but example apart from pure also by the properties of the active substance and of chlorexidine,chlorhexidine is available as theindividual chewing the gum. The chewing gum – different salts with different . A The water content of gum base isvery low and the specialcompound or pro-drug may be obtained by gum binds lipophilic substances very firmly. In order formulating a complex with an activelipophilic to obtain theoptional formulation it is possible to substance, e.g. by using cyclodextrines. This will 1. Decrease the release rate of highly result in a compound withhigher water solubility hydrophilic substances and consequently increased release. It is also 2. Increase the release rate of lipophilic possible toincrease or delay the release of an substances active substance by changing the physical 3. Achieve a more complete release of formthrough a variety of coating and lipophilic substances encapsulating techniques of the substance 4. Prolong the release particles.A hydrophilic or a hydrophobic coating 5. Changing the water solubility of the active may encapsulate the active substance. Toreduce substance will increase or delay therelease. the release rate a coating with ethyl cellulose can Asimilar effect may be obtained by changing the be used. hydrophilic/lipophilic balance of thechewing gum 7. The individual: For medical chewing gum as for formulation. The simplest way of achieving this is to other pharmaceutical products isan inter-patient increase ordecrease the amount of gum base. An variance. Additional to conventional increase in the gum base will make theformulation pharmaceutical formulations,other inter-patient more lipophilic and thus reduce the release rate of a variations apply for a chewing gum formulation. given active substance. In principle, it is possible to When theindividual is chewing the gum it may be manufacture products with a very low gumbase regarded as an extraction process.Consequently, content, but in practice a portion of chewing gum the release is related to the time the gum is being containing less than 20% gumbase will have inferior chewed to thefrequency and intensity by which chewing properties and may not be considered a the individual is chewing, and it depends on viableformulation. Instead of changing the gum base theamount and composition of the individual’s content, it is far more effective tochange the release saliva. properties by adding solubilizers to the formulation. This methodenables release from the chewing gum of PHARMACEUTICAL SIGNIFICANCE OF even highly insoluble substances, e.g.Miconazole. MEDICATED CHEWINGGUMS However using solubilizers requires specially Prevention and cure of oral disease are obvious designed gum bases as thesolubilizer affect the targets for chewing gum formulations.Chewing gum texture of chewing gum. This may result in residual can release an active substance at a controlled rate productbecoming soft to an unacceptable degree after over an extendedperiod of time providing a a very short period of chewing. Othermethods are prolonged local effect. available for instance nicotine can be formulated as

356 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______1. Sugar free chewing gum is known to be action and lead directly in to systematic beneficial to dental health. It has been circulation. Chewing gumpromotes buccal shownthat use of sugarfree chewing gum absorption by releasing active substances at after meals re-elevates plaque. pH plays carefully controlledrates, thus allowing for animportant role in the development of extended exposure in the oral cavity. dental caries. Therefore, in caries 6. A study of pharmacokinetics of nicotine preventionprograms, sugar-free chewing chewing gum indicated that some of gum is recommended after meals and snacks thenicotine was not absorbed through route as asupplement to tooth brushing. but was swallowed and underwent first- 2. Indications for fluoride chewing are passmetabolism. It was estimated that prevention of dental caries in children approximately 80% of the nicotine released influoride deficient areas, in adults with a fromthe chewing gum was absorbed through high incidence of caries and in patients buccal route. withxerostomia. 7. Successful treatment of minor pains, 3. Chlorhexidine chewing gum can be used for headaches, pains of colds, muscular ache, alleviations of gingivitis, periodontitisand etc.requires rapid absorption of therapeutic other oral and pharyngeal infections. It can doses of active substance. Chewing gum as also be used for inhibition of plaque growth adrug delivery system could be beneficial in and has proven valuable in oral health care minor pain treatment, when of the elderly. Furthermore,chlorhexidine in Buccalabsorption results in fast onset of a chewing gum formulation gives less action and reduces the risk of staining of the teeth and ismore convenient gastrointestinal sideeffects. to use than a chlorhexidine mouth rinse. The 8. The bioavailability of acetylsalicylic acid in chlorhexidine releasedby chewing is a chewing gum formulation relative toan distributed evenly in the oral cavity and is unbuffered tablet formulation has been present there for aprolonged time. The bitter determined. Absorption from the taste of chlorhexidine can be masked quite chewinggum formulation was shown to be well inachieving gum formulation. faster than absorption from the tablet, 4. Clinical trials involving patients with oral andconsequently, a chewing gum candidia sis have shown that formulation may provide faster pain relief. miconazolechewing gum is at least as 9. Several chewing gum formulations efficient as miconazole oral in the containing caffeine, guarana or chromium treatment of fungalinfections in the mouth. areavailable. Caffeine and guarana are Furthermore, patients preferred chewing central stimulating anorectic agents that gum to oral gel dueto convenience and havebeen proved to increase the metabolic fewer side effects. rate. Moreover, they stimulate lipolysis, 5. Chewing gum as a drug delivery system also have athermogenic effect (increase energy provides benefits to systemic drugdelivery, expenditure) and reduce the feeling of especially if the active substance is absorbed hunger. through the buccal mucosa,fast and acute 10. Chromium is claimed to reduce the carving treatment, convenience, no need for water for food due to an improved bloodglucose and thereby easyadministration – anytime balance. Chewing gum has been proven anywhere – reduced risk of gastrointestinal efficient in the treatment involvinginstant side effects.These benefits apply not only to raving and “oral habits”. Hence there is a the treatment of adults, but also to the rationale for administering weightreducing treatment ofchildren and adolescents. active substance in a chewing gum Systemic effect of active substances released formulation. from chewinggum can be achieved in two 11. Allergy, nausea, motion sickness, diabetes, ways. In the “traditional” way by anxiety, dyspepsia, osteoporosis, andcough swallowing the activesubstances, or via and cold are all indications for which absorption through the oral mucosa. The chewing gum as a drug delivery latter is of specialinterest, as buccal systemcould be beneficial. absorption avoids first-pass hepatic 12. Chewing gum containing antacids or metabolism of the activesubstance, it could mucolytics also presents advantages provide better bioavailability. Buccal forpatients. absorption may also lead tofast onset of the

357 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______13. Chewing gum as a drug delivery system treatment for somedisease was surgical procedure but offers convenience in now more and more disease can be treated withNovel thetreatment/prevention of motion sickness Drug Delivery Systems. Generally, it takes time for a and nausea. Medicated chewing new drug delivery systemto establish itself in the gumcontaining dimenhydtinate for motion market and gain acceptance by patients, however sickness is already on the market, chewinggum is believed to manifest its position as a however,active substances like scopolamine, convenient and advantageous drug metoclopramide, ondansetron and delivery system as it meets the high quality standards dolasetronmay be candidates for a chewing of pharmaceutical industry andcan be formulated to gum formulation for the obtain different release profiles of active substances. treatment/prevention ofmotion sickness and Thepotential of MCG for buccal delivery, fast onset nausea. of action and the opportunity forproductline 14. Several chewing gum formulations extension makes it an attractive delivery form. containing calcium are available on the Reformulation of anexisting product is required for market.Adolescents constitute a potential patent protection, additional patient benefits target group for a calcium chewing gum as andconservation of revenues. thecalcium intake of young people is often very low. Calcium chewing gum with SUMMARY AND CONCLUSION apleasant flavour is an attractive and Thus, it can be concluded that the chewing gum can convenient alternative to tablets. be used, as a carrier for vastcategories of drugs where 15. Miconazole has also been formulated as extended release and the local action is desired. chewing gum and these formulations Chewinggum can be used without water, at any time. havebeen used in clinical trials. Medicated Chewing gums can produceboth local 16. As Propranolol exhibits first-pass effects as well as systemic effects in the oral cavity. metabolism, a chewing gum formulation They can be used forthe purpose of taste masking of was seenas a viable option to obtain buccal certain drugs too. absorption. REFERENCES SAFETY ASPECTS 1. Michael J.R, Jonathan H and Michael S.R, Generally, today it is perfectly safe to chew chewing “Modified- Release Drug gum. Previously, hard chewinggum has caused DeliveryTechnology”, New York: Marcel broken teeth. Extensive chewing for a long period of Dekker, 2002, 419-429. time may causepainful jaws muscle, and extensive 2. Silagy C, Lancaster T, Stead L, Mant D, use of containing chewing gum Fowler G, “Nicotine replacementtherapy for maycause diarrhea. Long term frequent chewing of smoking cessation”, Cochrane Database gum has been reported to causeincreased release of Syst Rev,2001; Vol-3,CD000146. mercury vapors from dental amalgam fillings. 3. European Pharmacopoeia, 3rd ed. However,medicated chewing gum does not normally 4. Morjaria Y, Irwin WJ, Barnett PX, Chan RS require extensive chewing, orconsumption to great and Conway BR “ In Vitro Releaseof extent. Flavors, colour etc. may cause allergic Nicotine From Chewing Gum reactions. Formulations”, Dissolution Technologies, Overdosing by use of chewing gum is unlikely 2004;12-15. because a large amount of gum has tobe chewed in a 5. Conway B, “Chewing Gum as a Drug short period of time to achieve this. Swallowing Delivery System”, The Drug pieces of medicatedchewing gum will only cause DeliveryCompanies, Report minor release of the drug because the drug can only Autumn/Winter, 2003; 33-35. bereleased from the gum base by active chewing. As 6. Lee W. W, “Chewing gum as a delivery a general rule, medicated chewinggum (like other vehicle for pharmaceutical andnutraceutical medicines) should be kept out of reach of children, if substances”, Pharm Tech On-line, 2001; 2: required; drugdelivery may be promptly terminated 1-11. byremoval of the gum. 7. Zyck D.J., Greenberg; M.J., Barkalow D.G., Marske S. W., Schnell P. G.,Mazzone P. FUTURE TRENDS “Method of making coated chewing gum Chewing gum not only offers clinical benefits but products containing variousantacids”. US also is an attractive, discrete andefficient drug Patent 2003; 6645535. delivery system. A few decades ago, the only

358 www.ijapbc.comIJAPBC – Vol. 2(2), Apr- Jun, 2013 ISSN: 2277 - 4688 ______8. Jacobsen J., Christrup L.L., Jensen N-H, Crit Rev Oral Biol Med, 1999; 10(3):405- “Medicated Chewing Gum: Pros andCons”, 19. Am J Drug Deliv, 2004; Vol 2 (2):75-88. 20. 9. Athanikar N. K., Gubler S. A, “Process for hristrup LL, Rasmussen SN, Rassing MR, manufacturing a pharmaceuticalchewing “Chewing gum as a drug deliverysystem”. gum”, US Patent 2001; 6322828. Farmaci. Sci Ed, 1988; 16: 44-47. 10. Mochizuki Keizo, Yokomichi Fumio, 21. “Process for the preparation of oodford DW, LeskoLJ, “Relative chewinggum”, US Patent 1976; 4000321. bioavailability of aspirin gum”, J Pharm 11. http://www.spipharma.com/ProductsFolder/ Scie,1981; 70(12):1341-1343. 120ParmaGum/120Pharmagum.html. 22. 12. CherukuriSubraman R., BikkinaKirshnayya, yrpin HT, Russell MP, Witkewitz DL, “Tabletted chewing gumcomposition and Johnson SS, Ream RL, Corriveau method of preparation”, US Patent 1988; CL,“Caffeine coated chewing gum product 4753805. and process of making”, US Patent: 13. NaikHeema,GuptaStuti, “Medicated 2002;6444241. Chewing Gums- Updated 23. Review”,International Journal of Pharma eibel K, Schaffler K, Reitmeir P, Golly I, “A Research and Development, 2011; 2 (8), 66- randomised, placebo-controlledstudy 76. comparing two formulations of 14. British Pharmacopoeia, 3rd ed., 2001, 1778, dimenhydrinate with respect to efficacy A252.15. Dodds, M.W.J., Hsieh, S.C., inmotion sickness and sedation”. Johnson, D.A., “The effect on Arzneimittelforschung, 2002; 52(7):529-36. increasedmastication by daily gum chewing 24. on salivary gland output and dental ilagy C, Lancaster T, Stead L, Mant D, plaqueacidogenicity”, J. Dent. Res. 1991; Fowler G, “Nicotine replacementtherapy for 70, 1474–1478. smoking cessation”, Cochrane Database 15. Eisenstadt, B., Cash, A.P., Bakal, I.A., Syst Rev, 2001 ; Vol- 3,CD000146. “Chewing gum Containing 25. coughsuppression agent”, U.S. Patent, mith AJ, Moran J, Dangler LV, Leight RS, December 1998; 5846557. Addy M, “The efficacy of an 16. Pedersen M, Rassing MR, “Miconazole antigingivitischewing gum”, J chewing gum as a drug deliverysystem”, ClinPeriodontol, 1996; Vol-23(1):19-23.27. Drug DevInd Pharm, 1991; 17(3), 411-20. Oliveby A, Ekstrand J, Lagerlof F, “Effect 17. Woodford DW, LeskoLJ, “Relative of salivary flow rate on salivaryfluoride bioavailability of aspirin gum”, J clearance after use of a fluoride-containing PharmScie, 1981; 70(12):1341-1343. chewing gum”, Caries Res,1987; 21(5): 393- 18. Tyrpin HT, Russell MP, Witkewitz DL, 401. Johnson SS, Ream RL, Corriveau 26. CL,“Caffeine coated chewing gum product ertalik F, Bonorden R, “Salivary levels of and process of making”, US Patent:2002; antibiotics from use of 6444241. neomycingramicidinchewing troches”, J 19. Imfeld T. “Chewing gum--facts and fiction: Pharm Sci, 1968; 57(3):530-531. a review of gum-chewing and oralhealth”.

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