A short Curriculum Vitae of the authors
Chewing Gum as a Drug Delivery System
Biradar S S1 Bhagavti S T1 Hukkeri V I 1 Rao K P 2 Gadad A P1
Introduction: Man has a habit of chewing the chewing gum since ancient times. Today it is one of the most popular dosage form, used for delivering the many active components.
The first medical chewing gum was introduced in market in 1928 consisting of aspirin an analgesic drug. However, chewing gum did not gain acceptance as a reliable drug delivery system until 1978, when nicotine chewing gum became available in 1980,
Most of the chewing gum were used for smoking cessation (containing the nicotine) and also used for oral and dental hygiene (consisting of fluoride and carbamide etc).
Chewing gum can be used as drug delivery for many active components. With the inclusion of medical chewing gum in the European Pharmacopoeia in 1998, have further contributed to the acceptance of this method of drug delivery.
Today, medical chewing gum meets the same high-quality standards as tablets and can be formulated to obtain different release profiles of active substances, thus enabling distinct patient group targeting.
What are the ingredients in chewing gum?
Active substances and additives sweeteners like
sorbitol mannitol and suitable fruity flavours and nonsticky Gum Base The gum base is the insoluble part left in
the mouth while chewing and it is a polymer. The gum base is made of
resins from trees, latexs or the milky juices from plants, and manmade
polymers. If the gum base is chicle from the sapodilla tree, this product
is being harvested in
Cuts on the sapodilla tree let the sap run into a collection bucket.
Chicle is boiled over an open fire in the rainforest to evaporate some of the excess water. Once it is thick and taffy-looking, it is packed into wooded forms to make blocks. These blocks are shipped to some American chewing gum manufacturers. Chicle is a rubbery latex or polyterpene. Polyterpenes are composed of thousands of C5H8 isoprene subunits.
Today, the gum base could also be made from styrene butadiene, poly (vinyl acetate) or polyethylene. The sugar is for sweetening the product. The corn syrup keeps the gum fresh and flexible. Softeners or fillers such as vegetable oils help to blend the ingredients and retain moisture. Sugar free gum has sorbitol, mannitol, aspartame or saccharin instead of sugar. The gum base determines the basic characteristics of the product example texture whether it is soft? Does it crumble? Does it stick to the teeth?
Why we use chewing gum as a drug delivery system?
There are many reasons for selecting the chewing as a drug delivery system, the following are the some reasons highlighted.
1) Easy for administration without water promotes higher patient compliance.
2) Children and for patients who find swallowing tablets difficult are obvious.
3) Local effect
4) Systemic Effect
5) Fast onset of action
6) Less side effects
7) Less risk of overdosing
8) Effective on Dry mouth
High acceptance in children
Many children find it difficult to swallow tablets. To overcome this problem, liquid formulations have been developed, however, administering liquid formulations may be difficult and circumstantial as well. A chewing gum formulation is an obvious alternative. In a chewing gum formulation, it is most often possible to disguise the bitter/bad taste of the active substance, making it a pleasant experience for the child. However, it is important that the child chews the chewing gum for the prescribed period of time. Compared to a liquid formulation, chewing gum also provides easier Storage as there is no risk of microbial contamination.
Prevention and cure of oral diseases are obvious targets for chewing gum formulations. Chewing gum can release an active substance at a controlled. Sugar-free chewing gum is known to be beneficial to dental health. It has been shown that use of sugar-free chewing gum after meals re-elevates plaque pH 1
Indications for fluoride chewing gum are prevention of dental carries in Children in fluoride-deficient areas, in adults with a high incidence of carries, and in patients with xerostomia. The carries-preventive effect of fluoride chewing gum has been compared with the effect of placebo chewing gum in oral infections caused by bacteria or fungi are often seen, especially in patients with impaired immune system. Chlorhexidine Chewing gum can be used for treatment of gingivitis, peridontitis and other oral and pharyngeal infections4 it can also be used for inhibition of plaque growth and has shown Successful treatment of minor pains, headaches, pains of cold, muscular aches, etc. requires rapid absorption of therapeutic doses of the active substance. Chewing gum as a drug delivery system could be beneficial in minor pain treatment, when buccal absorption results in fast onset of action and reduces the risk of gastrointestinal side effects. The bioavailability of acetylsalicylic acid in a chewing gum formulation relative to an unbuffered tablet formulation has been determined8.
A chewing gum formulation may also be useful in the treatment of acute, strong pain. Bioavailability of methadione from a chewing gum formulation has been compared to a tablet formulation. There was no significant difference in the bioavailability of the two formulations9.
As no water is required, taking medication in chewing gum is very convenient and therefore suitable for acute treatment. The medication may be taken without regard to time and place, thus promoting compliance. Chewing gum does not draw attention to the medication, it is discrete and does not Stigmatize the patient.
Today, there is a trend towards higher patient involvement in drug administration and handling. Chewing gum is in line with this trend as it allows easy self-administration and does not prevent patients from living an active life. Further Clinical trials involving patients with oral candidosis have shown that miconazole chewing gum is at least as efficient as miconazole oral gel in the treatment of fungal infections in the mouth6,7.
Fewer side effects
Active substances absorbed buccally bypass the hepatic first pass metabolism, which may result in a higher bioavailability of the active substance. Thus, the equivalent efficacy may be obtained with a lower dosage, and consequently less side effects are expected. Further, a lower dosage may reduce the risks of interactions with other active substances. The controlled release rate also reduces the risk of side effects, as high plasma peak concentrations are avoided.
Effect on dry mouth
Dry mouth is a side effect of many types of medication (e.g. antidepressants), and it is also part of the symptomatology of several diseases (e.g. Sjögren’s syndrome). It is well known that chewing gum stimulates salivary secretion1, and a chewing gum formulation therefore partly alleviates this condition. Furthermore, as dry mouth increases the incidence of dental caries, chewing gum may also be beneficial to dental health. It has been shown that long-term activation of the salivary glands by chewing gum several It has been shown that long-term activation of the salivary glands by chewing gum several times per day for two months enhanced resting salivary flow, especially in individuals with low salivary flow1.
Less risk of overdosing
Chewing is required to release the active substance from chewing gum. If the chewing gum is swallowed accidentally, only limited amounts of the active substance will be released over a relatively long period of time, thus reducing the risk of high plasma peak concentrations and overdosing.
The Chewing gum can be used for therapeutic purposes by incorporating the various medicaments especially antiasthamatic and Nonsteroidal anti-inflammatory and antiobsedrugs.
Evaluation of chewing gum: The absorption of active substances through the buccal mucosa can be examined by both in vitro and in vivo methods. The most common in
vitro method involves an Using chamber, in which excised buccal mucosa from either humans or animals is placed as a barrier between two chambers.The transport of active substances across the mucosa is measured by withdrawal of samples from each chamber. Buccal mucosa from domestic pigs is recommended, mainly because of the morphological similarity in mucosa from the human and porcine oral cavities.
Likewise, a human TR146 cell culture model has proven a good in vitro model for investigating permeability, permeability mechanisms, effects of chemical enhancers, and toxic effects18.
The machines are driven by air and are set to a specific number and frequency of chews inside a water bath at 37 degrees Celsius, similar the temperature of saliva in a person's mouth. Once the gum is "chewed" the fluid is tested to see how much of the drug has been released. The results are used to evaluate effectiveness and to develop new gum products25
Buccal absorption of active substances can also be tested by various in vivo methods. Beckett and Triggs introduced a mouth wash procedure in 1967, in which a buffered solution of the active substance is swirled in the oral cavity for a known period of time23.
Subsequently, the solution is expelled and the oral cavity is rinsed with buffer. The difference between the amount of active substance contained in the original solution and the amount recovered is assumed to be the amount of active substance absorbed from the oral cavity. Since the introduction of this method, it has been improved by various modifications, however, the main limitation lies in the fact that the method cannot account for storage of active substances in the mucosa.
Another in vivo method involves a perfusion chamber, which is adhered to the buccal mucosa of the test person. The absorbed amount of active substance perfused through the chamber is calculated as the decrease in active substance24.
Though chewing gum as a drug delivery system has currently gained wide acceptance only within smoking cessation and oral healthcare, vast interest in this mode of drug delivery for a wide variety of other indications exists and continues to grow. Clinical trials have confirmed the advantages to be gained by exploiting the effects of chewing gum, per se, the convenience of the delivery and the possibilities of buccal absorption and local effect. Furthermore, one trial has indicated that chewing gum is possibly a safer drug delivery system for active substances that are susceptible to abuse. As chewing gum as a drug delivery system is to be expanded into additional therapeutic areas, it is important that the delivery form is acceptable to the end-users. Clinical trials and market research have proven this to be the case. In the coming years, new formulations will enter the market and chewing gum will become a much more common drug delivery system. _
Department of pharmaceutics Department of pharmaceutics
1. Imfeld, T. (1999) Crit. Rev. Oral Biol. Med. 10, 405-419.
2. Lamb, W.J. et al. (1993) Caries Res. 27, 111-116.
3. Sjögren, K. et al. (2002) Caries Res., in press.
4. Smith, A.J. et al. (1996) J. Clin. Periodontol. 23, 19-23.
5. Simons, D. et al. (1999) British Dent. J. 187, 612-615.
6. Rindum, J.L. et al. (1993) Scand. J. Dent. Res. 101, 386-390.
7. Rindum, J.L. et al., in preparation.
8. Woodford, D.W., Lesko, L.J. (1981) J. Pharm. Sci. 70, 1341-1343.
9. Christrup, L.L. et al. (1990) Acta Pharm. Nord. 2, 83-88.
10. Rassing, M.R. (1994) Adv. Drug Del. Rev. 13, 89-121.
11. Jensen, E.J. et al. (1991) Psychopharmacol. 104, 470-474.
12. Odusola, F. (1991) The
13. Olsson, H. et al. (1991) Acta Odontol. Scand. 49, 273-279.
14. Rhodus, N.L., Schuh, M.J. (1991) Oral Surg. Oral Med. Oral Pathol. 72, 545-549.
15. Avidan, B. et al. (2001) Aliment Pharmacol. Ther. 15, 151-155.
16. Schönfeld, J.v. et al. (1997) Digestion 58, 111-114.
Marcel Dekker, Inc.,
18. Nielsen, H.M. (2000) Ph.D. thesis, HCØ Tryk,
19. Nielsen, H.M. (2002) In: Lehr C.-M. (Ed.) Cell Culture Models of
Biological Barriers: In vitro Test Systems for Drug Absorption and Delivery,
Harwood Academic Publishers,
20. Collins, L.M.C., Dawes, C. (1987) J. Dent. Res. 66, 1300-1302.
21. Jacobsen, J. et al. (1995) Int. J. Pharm. 125, 165-184.
22. Nielsen, H.M., Rassing, M.R. (2002) Eur. J. Pharm. Sci., submitted.
23. Beckett, A.H., Triggs, E.J. (1967) J. Pharm. Pharmacol. 19, 31S-41S.
24. Rathbone, M.J. et al. (1996) In: Rathbone, M.J. (Ed.) Oral Mucosal
Marcel Dekker, Inc.,
25. Dr. Gord McKay September 2004www.innovationplace.com
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