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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 31  |  Issue : 1  |  Page : 62-65

Medicated chewing gums - A novel targeted drug delivery


1 Department of Oral Medicine and Radiology, College of Dental Sciences, Rau, Indore, Madhya Pradesh, India
2 Private Practitioner, Oral Medicine and Radiology, Dombivali, Maharashtra, India
3 Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere, Karnataka, India
4 Private Practitioner, Oral Medicine and Radiology, Referral Hospital and Community Health Centre, Lodhika, Rajkot, Gujarat, India

Date of Submission29-Jun-2018
Date of Acceptance14-Oct-2018
Date of Web Publication23-Apr-2019

Correspondence Address:
Dr. Nimesh Jain
194, Alok Nagar, Kanadia Road, Indore - 452 016, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_111_18

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   Abstract 


The potential of medicated chewing gum (MCG) for buccal delivery, fast onset of action makes it an attractive delivery form. It is considered as vehicle or a drug delivery system to administer active principles that can improve health and nutrition. Chewable tablets and chewing gum (CG) permit more rapid therapeutic action compared to per-oral dosage forms. Chewable tablets and CGs have been very well received by the parents for use in children with full dentition. MCG is feasible in local treatment of diseases of oral cavity as well as treatment of systemic conditions. This newer drug delivery system could be a boon in treating oral diseases as it is a non-invasive mode of drug delivery.

Keywords: Drug delivery, medicate chewing gum, noninvasive


How to cite this article:
Jain N, Jadhav M, Annigeri RG, Pipaliya PR. Medicated chewing gums - A novel targeted drug delivery. J Indian Acad Oral Med Radiol 2019;31:62-5

How to cite this URL:
Jain N, Jadhav M, Annigeri RG, Pipaliya PR. Medicated chewing gums - A novel targeted drug delivery. J Indian Acad Oral Med Radiol [serial online] 2019 [cited 2019 Sep 17];31:62-5. Available from: http://www.jiaomr.in/text.asp?2019/31/1/62/256887



Medicated chewing gum (MCG) is a novel drug delivery system containing masticatory gum base with pharmacologically active ingredient and intended to use for local treatment of mouth diseases or systemic absorption through oral mucosa. MCG is considered as vehicle or a drug delivery system to administer active principles that can improve health and nutrition.

Pharmacological active agents or drugs are formulated into variety of dosage form such as tablets, capsules, injectables, inhalers, ointments, etc., considering physicochemical, pharmacokinetic, pharmacodynamic parameters, and biopharmaceutical aspects of drugs. In addition to its confectionary role, chewing gum (CG) also has proven value as a delivery vehicle for pharmaceutical and nutraceutical ingredients.[1]

Chewable tablets and CGs have been very well received by the parents for use in children with full dentition. Children in particular may consider CG as a more preferred method of drug administration compared with oral liquids and tablets. The use of MCG is feasible in local treatment of diseases of oral cavity as well as treatment of systemic conditions.


   Medicated Chewing Gum Top


CG has been used for centuries to clean the mouth and freshen the breath.[2] The first patent for the production of CG was filed in 1869 and was issued to Mr. W. F. Semple in Ohio under U. S. Patent No. 98,304. A MCG containing acetyl salicylic acid was commercially introduced in 1928.[3]

In 1991, CG was approved as a term for pharmaceutical dosage form by the commission of European council.

MCGs are solid, single dose preparations with a base consisting mainly of gum that is intended to be chewed but not swallowed. They contain one or more active substances that are released by chewing and are intended to be used for local treatment of mouth diseases or systemic delivery after absorption through the buccal mucosa.[4]


   Components of Medicated Chewing Gum Top


CG is a mixture of natural or synthetic gums and resins, sweetened with sugar, corn syrup, artificial sweeteners, and may also contain coloring agents and flavor. The basic raw material for all CG is natural gum chicle, obtained from the sapodilla tree. Chicle is very expensive and difficult to procure therefore other natural gum or synthetic materials such as polyvinyl acetate and similar polymers can be used as gum base.

Typically CG comprises two parts[5]

  1. Water insoluble chewable gum base portion
  2. Water-soluble bulk portion.



   Manufacturing Processes Top


Different methods employed for the manufacturing of CG[6],[7] can be broadly classified into three main classes namely

  1. Conventional/traditional method (Melting)
  2. Freezing, grinding, and tableting method
  3. Direct compression method.



   Factors Affecting Release of Active Ingredient Top


  1. Contact Time: The local or systemic effect is dependent on time of contact of MCG in oral cavity. In clinical trial, chewing time of 30 min was considered close to ordinary use
  2. Physicochemical properties of active ingredient: 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 that affect the drug release from MCG may vary from person to person. In-vitro study prescribed by European Pharmacopoeia suggests 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.[4]



   Therapeutic Uses of Medicated Chewing Gum Top


  1. The use of sugar free gum to counteract dental caries by stimulation of saliva secretion has led to a more widespread use and acceptance of gums. It has been proved that chewing non-MCGs increases plaque pH, stimulates saliva flow, and decrease decay. Prevention and cure of oral disease are obvious targets for CG formulations. It can control the release rate of active substances providing a prolonged local effect[8],[9],[10]
  2. Fluoride containing gums have been useful in preventing dental caries in children and in adults with xerostomia[11]
  3. MCGs containing chlorhexidine (CHX) for treatment of gingivitis and plaque have been available. The use of MCG in the treatment of oral infections has also been reported. CHX CG offers numerous flexibility in its formulation as it gives less staining of the teeth and is distributed evenly in the oral cavity. The bitter taste of CHX can be masked quite well in a CG formulation[9],[12]
  4. For systemic effect in conditions such as Vitamin C deficiency, pain and fever alertness, motion sickness, as well as for local effect in the conditions such as plaque acid neutralization, fresh breath, disinfection, anticaries, antiplaque, antifungal, and antibacterial are available[13],[14]
  5. Obesity- Active substances such as chromium, guaran, and caffeine are proved to be efficient in treating obesity. Chromium is claimed to reduce craving for food because of an improved blood-glucose balance. Caffeine and guaran stimulate lipolysis and have a thermogenic effect (increased energy expenditure) and reduce feeling of hunger[15],[16]
  6. In addition, gums are available for smoking cessation.[17]



   Merits Of Medicated Chewing Gum Top


  1. Excellent for acute medication
  2. Water is not required to take this medication. Therefore, it can be taken anywhere, and hence, high patient compliance[18]
  3. It need not be swallowed. Therefore, it can be a boon for patient with dysphagia[3]
  4. Helps preventing dry mouth candidiasis and caries[18]
  5. Highly acceptable by children
  6. Increases the bioavailability of drugs by avoiding first pass metabolism[3]
  7. Fast onset because of the rapid release of active ingredients in buccal cavity and subsequent absorption in systemic circulation[18]
  8. Gum does not reach the stomach. Hence, gastro intestinal tract (GIT) suffers less from the effects of excipients
  9. Stomach does not suffer from direct contact with high concentrations of active principles, thus reducing the risk of intolerance of gastric mucosa[3]
  10. Fraction of product reaching the stomach is conveyed by saliva delivered continuously and regularly. Therefore, duration of action is increased
  11. Aspirin, dimenhydrinate, and caffeine show faster absorption through MCG than tablets
  12. Gives local effect
  13. Increase the rate of saliva secretion. Stimulated saliva has a buffering capacity. Therefore, may help in reducing acidity of gastric fluid.



   Demerits of Medicated Chewing Gums Top


  1. Control over drug dosage is not sufficient. The risk of over dosage with MCGs compared with chewable tablets or lozenges that can be consumed in a considerable number and within much shorter period of time[2]
  2. Sorbitol present in MCG formulation may cause flatulence and diarrhea
  3. Additives in gum such as flavoring agent, cinnamon, can cause ulcers in oral cavity and licorice causes hypertension
  4. CHX oromucosal application is limited to short-term use because of its unpleasant taste and staining properties to teeth and tongue[19]
  5. CGs have been shown to adhere to different degrees to enamel dentures and fillers[20]
  6. Prolong chewing on gum may result in pain in facial muscles and earache in children.[21]



   Literature Overview Top


Literature shows few studies conducted in designing and testing the properties of these MCGs.

A study was conducted to assess the anti-plaque effect of CHX in CG on 12 dental hygiene students. Three types of CG were used; each CG measured 0.80gm. One containing 5 mg CHX acetate, one containing 5 mg CHX acetate in addition with hydrogen peroxide (H2O2) and third one was used as control with neither CHX acetate and H2O2 and only flavouring agent as base. During the 4-day test periods, no other oral hygiene measures were allowed than chewing 2 pieces of gum at the time for approximately 10 min, 5 times daily.[22]

At the beginning and at the end of each test period, the quantity of plaque was assessed using the plaque index, plaque wet weight, and the area of plaque on the tooth surface as criteria. It was concluded that use of both the CHX gum and the gum-containing CHX in addition to the H2O2 releasing agent had an excellent plaque growth inhibiting effect during the 4-day test periods but also that the CHX gum had unpleasant taste.

Later in a study in 2008, the researchers prepared a new formulation of CHX gluconate CG that gave both anti-plaque effectiveness and an acceptable taste.[23]

A systematic review was conducted by Keukenmeester RS et al. from MEDLINE-PubMed, Cochrane-CENTRAL, and EMBASE databases to check the effect of sugar-free CG on plaque and clinical parameters of gingival inflammation. It was concluded that the use of sugar-free CG as an adjunct to tooth brushing provides a small but significant reduction in plaque scores. Chewing sugar-free gum showed no significant effect on gingivitis scores. In the absence of brushing, no effect on plaque and gingivitis scores could be established.[24]

In another study, the researchers proved that the use of CHX CG significantly reduced dental plaque formation compared to the use of similar xylitol and sorbitol products in a double-blind three-treatment crossover design employing a 6-day trial period without mechanical oral hygiene measures.

Further, studies are under progress to check if the use of xylitol CG in mothers may delay the transmission of  Streptococcus mutans Scientific Name Search  infants.[25]


   Smoking Cessation Top


CG formulation containing nicotine, lobeline, and silver acetate has been clinically tested as aids to smoking cessation.[26] It is a therapeutic agent intended to help smokers break the psychological habit of smoking by reducing the nicotine withdrawal symptoms normally experienced when smoking is stopped.

The optimal dosage form is selected according to the following table:

Directions for use:

  1. One piece of gum should be chewed until the taste becomes strong
  2. The CG should be rested between the gum and cheek
  3. When the taste fades, chewing should commence again
  4. The chewing routine should be repeated for 30 min.


Normally, treatment should continue for at least for 3 months. After three months, the user should gradually cut down the number of pieces chewed each day until they have stopped using the product. Treatment should be discontinued when the dose has been reduced to 1–2 pieces of gum per day. Nicotine gum is sugar free.


   Oral Candidiasis Top


Fungal infections have become major causes of morbidity and mortality among immunocompromised patients.[27] Oral candidiasis is a fungal infection caused by the opportunistic pathogen named Candida albicans. Conventional available treatments for oral candidiasis include topical antifungal azoles such as miconazole. Although increase of resistant microorganisms to conventional treatment is becoming a challenge, researchers are trying to identify potential drugs and alternatives treatments with better and improved therapeutic effects and fewer adverse effects. Studies are being done to develop a MCG with a combination of essential oils as active substances for the effective treatment of oral candidiasis.


   Other Oromucosal Lesions and Conditions Top


Studies are being conducted to formulate aloe vera CGs to treat oromucosal lesions such as oral lichen planus, ulcers, and abscesses caused by cancer chemotherapy and mucositis caused by radiotherapy.[28]


   Safety Aspect Top


Over usage of the CGs can lead to pain in the masticatory muscles, and if overused over a longer period of time can lead to hypertrophy of the muscles. MCG like other drugs should be carefully taken under the supervision of the physician and kept away from the reach of children.


   Conclusion Top


CG not only offers clinical benefits but also is an attractive, discrete, and efficient drug delivery system. A few decades ago, the only treatment for some disease was surgical procedure but now more and more disease can be treated with novel drug delivery systems. In general, it takes time for a new drug delivery system to establish itself in the market and gain acceptance by patients. However, CG is believed to manifest its position as a convenient and advantageous drug delivery system as it meets the high quality standards of pharmaceutical industry and can be formulated to obtain different release profiles of active substances.

The potential of MCG for buccal delivery, fast onset of action, and the opportunity for product-line extension makes it an attractive delivery form. Reformulation of an existing product is required for patent protection, additional patient benefits, and conservation of revenues.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Morjaria Y, Irwin WJ, Barnett PX, Chan RS, Conway BR.In vitro release of nicotine from chewing gum formulations. Dissolution Technol, 12-15, May 2004.  Back to cited text no. 1
    
2.
Jacobsen J, Christrup LL, Jensen N-H. Medicated chewing gum: Pros and cons. Am J Drug Deliv 2004;2:75-88.  Back to cited text no. 2
    
3.
Conway B. Chewing gum as a drug delivery system. The drug delivery companies report Autumn/Winter, 2003. p. 33-5.  Back to cited text no. 3
    
4.
European Pharmacopoeia. Strasbourg: European directorate for the quality of medicines. Chewing Gums: Medicated. 5th ed. 2004. p. 260 and 601.  Back to cited text no. 4
    
5.
Zyck DJ, Greenberg MJ, Barkalow DG, Marske SW, Schnell PG, Mazzone P. Method of making coated chewing gum products containing various antacids. US Patent 2003;6:645,535.  Back to cited text no. 5
    
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Athanikar NK, Gubler SA. Process for manufacturing a pharmaceutical chewing gum. US Patent 2001;6:322,828.  Back to cited text no. 6
    
7.
Keizo M, Yokomichi Fumio: Process for the preparation of chewing gum. US Patent 1976;4:000,321.  Back to cited text no. 7
    
8.
Pedersen M, Rassing MR. Miconazole chewing gum as a drug delivery system. Drug Dev Ind Pharm 1991;17:411-20.  Back to cited text no. 8
    
9.
Parmar VW, Thosar M. A comprehensive review on: Medicated chewing gum. Int J Res Pharma Biomedical Sci 2012;3:894-907.  Back to cited text no. 9
    
10.
Nikam VK, Kotade KB, Gaware VM, Dolas RT, Dhamak KB, Somwanshi SB, et al. Medicated chewing gum as anovel drug delivery system-A review. Pharmacologyonline 2011;403-13.  Back to cited text no. 10
    
11.
Oliveby A, Ekstrand J, Lagerlof F. Effect of salivary flow rate on salivary fluoride clearance after use of a fluoride-containing chewing gum. Caries Res 1987;21:393-401.  Back to cited text no. 11
    
12.
Christrup LL, Rasmussen SN, Rassing MR. Chewing gum as a drug delivery system. Farmaci Sci Ed 1998;16:44-7.  Back to cited text no. 12
    
13.
Woodford DW, Lesko LJ.: Relative bioavailability of aspirin gum. J Pharm Sci 1981;70:1341-3.  Back to cited text no. 13
    
14.
Seibel K, Schaffler K, Reitmeir P, Golly I. A randomised, placebo-controlled study comparing two formulations of dimenhydrinate with respect to efficacy in motion sickness and sedation. Arzneimittelforschung 2002;52:529-36.  Back to cited text no. 14
    
15.
Imfeld T. Chewing gum--facts and fiction: A review of gum-chewing and oral health. Crit Rev Oral Biol Med 1999;10:405-19.  Back to cited text no. 15
    
16.
Aslani A, Rostami F. Medicated chewing gum: A novel drug delivery system. J Res Med Sci 2015;20:403-11.  Back to cited text no. 16
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17.
Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2001:CD000146.  Back to cited text no. 17
    
18.
Morjaria Y, Irwin WJ, Barnett PX, Chan RS, Conway BR.In vitro release of nicotine from chewing gum formulations. Dissolution Technol 2004;11:12-5.  Back to cited text no. 18
    
19.
Addy M, Roberts WR. Comparison of the bisbiguanide antiseptics alexidine and chlorhexidine. II. Clinical and in vitro staining properties. J Clin Periodontol 1981;8:220-30.  Back to cited text no. 19
    
20.
Munksgaard EC, Nolte J, Kristensen K. Adherence of chewing gum to dental restorative materials. Am J Dent 8:137-9.  Back to cited text no. 20
    
21.
Weil AT. Coca leaf as a therapeutic agent. Am J Drug Alcohol Abuse 1978;5:75-86.  Back to cited text no. 21
    
22.
Ainamo J, Etemadzadeh H. Prevention of plaque growth with chewing gum containing chlorhexidine acetate. J Clin Periodontol 1987;14:524-7.  Back to cited text no. 22
    
23.
Kolahi J, Soolari A, Ghalayani P, Varshosaz J, Fazilaty M. Newly formulated chlorhexidine gluconate chewing gum that gives both anti-plaque effectiveness and an acceptable taste: A double blind, randomized, placebo-controlled trial. J Int Acad Periodontol 2008;10:38-44.  Back to cited text no. 23
    
24.
Keukenmeester RS, Slot DE, Putt MS, Van der Weijden GA. The effect of sugar-free chewing gum on plaque and clinical parameters of gingival inflammation: A systematic review. Int J Dent Hyg 2013;11:2-14.  Back to cited text no. 24
    
25.
O'Connell AC. Use of xylitol chewing gum in mothers may delay transmission of mutans streptococci to their infants. J Evid Based Dent Pract 2011;11:62-4.  Back to cited text no. 25
    
26.
Drugs information online Drugs.com accessed on 27-01-2013.  Back to cited text no. 26
    
27.
Ozokwere J, Olivier E, Gedeon M, Demana P. Formulation of a chewing gum for treating oral candidiasis. J Oral Hyg Health 2017;5:1.  Back to cited text no. 27
    
28.
Aslani A, Ghannadi A, Raddanipour R. Design, formulation and evaluation of Aloe vera chewing gum. Adv Biomed Res 2015;4:175.  Back to cited text no. 28
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