You are hereMedicated Chewing Gum: A Review
Medicated Chewing Gum: A Review
The stability of chewing gum is comparable to that of most other solid delivery systems. Chewing gum normally contains little water (2.5%). If the water content is very critical for the stability of drug, the chewing gum can be manufactured without water (less 0.2%). This will however, often make the product hygroscopic and will affect the texture. The low water content also inhibits microbial growth in the chewing gum during storage. Furthermore, the product can be protected against oxidation by a sealed coat and by an appropriate packing. For every temperature-labile component, e.g. enzymes, the process temperature of 50-600 C during mixing may create a stability problem. It is however possible to operate the process at a lower temperature to avoid this issue.
As per specifications given in European Pharmacopoeia.
1) Test for Uniformity of Content: Unless otherwise prescribed or justified and authorized medicated chewing gum with content of 2 mg or less than 2 percent of the total mass of gum comply with test.
2) Uniformity of mass: Uncoated medicated chewing gum and unless otherwise justified and authorized coated medicated chewing gum comply with the test for uniformity of mass of single- dose preparations.
3) Drug release from medicated chewing gum: It has been reported commercially that the drug release from medicated chewing gum as per the specification given in European Pharmacopoeia and is determined by applying a mechanical kneading procedure to a piece of gum placed in a small chewing chamber containing a known volume of buffer solution.
FACTORS AFFECTING RELEASE
The release rate of an active substance is determined not only by the formulation of the chewing gum but also by the properties of the active substance and of the individual chewing the gum. The chewing gum – The water content of gum base is very low and the gum binds lipophilic substances very firmly. In order to obtain the optional formulation it is possible to
1. Decrease the release rate of highly hydrophilic substances
2. Increase the release rate of lipophilic substances
3. Achieve a more complete release of lipophilic substances
4. 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 minutes was considered close to ordinary use.
5. 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.
6. 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.
7. Changing the water solubility of the active substance will increase or delay the release. A similar effect may be obtained by changing the hydrophilic/lipophilic balance of the chewing gum formulation. The simplest way of achieving this is to increase or decrease the amount of gum base. An increase in the gum base will make the formulation more lipophilic and thus reduce the release rate of a given active substance. In principle, it is possible to manufacture products with a very low gum base content, but in practice a portion of chewing gum containing less than 20% gum base will have inferior chewing properties and may not be considered a viable formulation. Instead of changing the gum base content, it is far more effective to change the release properties by adding solubilizers to the formulation. This method enables release from the chewing gum of even highly insoluble substances, e.g. Miconazole. However using solubilizers requires specially designed gum bases as the solubilizer affect the texture of chewing gum. This may result in residual product becoming soft to an unacceptable degree after a very short period of chewing. Other methods are available for instance nicotine can be formulated as complex bound to a cation exchange resin leading to a prolonged release. This ion exchange principle could of course, also be used for other ionic substances. It is also possible to granulate the active substance with hydrophilic components, melted lipids, or to mix the active substance with a melted polymer.
8. The active substance: The release rate of an active substance depends on the solubility of the active substance in water and saliva. Highly hydrophilic substance will be almost completely released within 10 to 15 minutes. Substances with solubility in water or less than 0.1 – lg/100ml are lipophilic components of the gum base and thereby show a slow and incomplete release. Active substances may be found in the form of salts or compounds with different solubilities, e.g. pro-drugs, thus the compound offering the best properties for achieving optimal release may be selected. Chlorhexidine can serve as an example apart from pure chlorexidine, chlorhexidine is available as different salts with different solubility. A special compound or pro-drug may be obtained by formulating a complex with an active lipophilic substance, e.g. by using cyclodextrines. This will result in a compound with higher water solubility and consequently increased release. It is also possible to increase or delay the release of an active substance by changing the physical form through a variety of coating and encapsulating techniques of the substance particles. A hydrophilic or a hydrophobic coating may encapsulate the active substance. To reduce the release rate a coating with ethyl cellulose can be used.
9. The individual: For medical chewing gum as for other pharmaceutical products is an inter-patient variance. Additional to conventional pharmaceutical formulations, other interpatient variations apply for a chewing gum formulation. When the individual is chewing the gum it may be regarded as an extraction process. Consequently, the release is related to the time the gum is being chewed to the frequency and intensity by which the individual is chewing, and it depends on the amount and composition of the individual’s saliva.
PHARMACEUTICAL SIGNIFICANCE OF MEDICATED CHEWING GUMS
Prevention and cure of oral disease are obvious targets for chewing gum formulations. Chewing gum can release an active substance at a controlled rate over an extended period of time providing a prolonged local effect.
1. 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 plays an important role in the development of dental caries. Therefore, in caries prevention programs, sugar-free chewing gum is recommended after meals and snacks as a supplement to tooth brushing.
2. Indications for fluoride chewing are prevention of dental caries in children in fluoride deficient areas, in adults with a high incidence of caries and in patients with xerostomia.
3. Chlorhexidine chewing gum can be used for alleviations of gingivitis, periodontitis and other oral and pharyngeal infections. It can also be used for inhibition of plaque growth and has proven valuable in oral health care of the elderly. Furthermore, chlorhexidine in a chewing gum formulation gives less staining of the teeth and is more convenient to use than a chlorhexidine mouth rinse. The chlorhexidine released by chewing is distributed evenly in the oral cavity and is present there for a prolonged time. The bitter taste of chlorhexidine can be masked quite well in achieving gum formulation.
4. Smoking cessation- Chewing gum formulation containing nicotine49, lobeline and silver acetate have been clinically tested as aids to smoking cessation. Nicotine is a natural alkaloid occurring in the leaves of tobacco plant. 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 formulation nicorette available as mint and classic with different flavor and dosage, is developed with ion- exchange resin, released 90% of drug after 30 min chewing (Russel et.al 1980). The release rate was controlled by the rate and vigour of chewing. Thus the patient can control the drug intake to match his needs. Increasing the pH of the mmedium in which it is dissolved can enhance nicotine absorption.
5. Clinical trials involving patients with oral candidia sis have shown that miconazole chewing gum is at least as efficient as miconazole oral gel in the treatment of fungal infections in the mouth. Furthermore, patients preferred chewing gum to oral gel due to convenience and fewer side effects.
6. Chewing gum as a drug delivery system also provides benefits to systemic drug delivery, especially if the active substance is absorbed through the buccal mucosa, fast and acute treatment, convenience, no need for water and thereby easy administration – anytime anywhere – reduced risk of gastrointestinal side effects. These benefits apply not only to the treatment of adults, but also to the treatment of children and adolescents. Systemic effect of active substances released from chewing gum can be achieved in two ways. In the “traditional” way by swallowing the active substances, or via absorption through the oral mucosa. The latter is of special interest, as buccal absorption avoids first-pass hepatic metabolism of the active substance, it could provide better bioavailability. Buccal absorption may also lead to fast onset of the action and lead directly in to systematic circulation. Chewing gum promotes buccal absorption by releasing active substances at carefully controlled rates, thus allowing for extended exposure in the oral cavity.
7. A study of pharmacokinetics of nicotine chewing gum indicated that some of the nicotine was not absorbed through route but was swallowed and underwent first-pass metabolism. It was estimated that approximately 80% of the nicotine released from the chewing gum was absorbed through buccal route.
8. Successful treatment of minor pains, headaches, pains of colds, muscular ache, etc. requires rapid absorption of therapeutic doses of 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.
9. The bioavailability of acetylsalicylic acid in a chewing gum formulation relative to an unbuffered tablet formulation has been determined. Absorption from the chewing gum formulation was shown to be faster than absorption from the tablet, and consequently, a chewing gum formulation may provide faster pain relief.
10. Several chewing gum formulations containing caffeine, guarana or chromium are available. Caffeine and guarana are central stimulating anorectic agents that have been proved to increase the metabolic rate. Moreover, they stimulate lipolysis, have a thermogenic effect (increase energy expenditure) and reduce the feeling of hunger.
11. Chromium is claimed to reduce the carving for food due to an improved blood glucose balance. Chewing gum has been proven efficient in the treatment involving instant raving and “oral habits”. Hence there is a rationale for administering weight reducing active substance in a chewing gum formulation.
12. Allergy, nausea, motion sickness, diabetes, anxiety, dyspepsia, osteoporosis, and cough and cold are all indications for which chewing gum as a drug delivery system could be beneficial.
13. Chewing gum containing antacids or mucolytics also presents advantages for patients.
14. Chewing gum as a drug delivery system offers convenience in the treatment/prevention of motion sickness and nausea. Medicated chewing gum containing dimenhydtinate for motion sickness is already on the market, however, active substances like scopolamine, metoclopramide, ondansetron and dolasetron may be candidates for a chewing gum formulation for the treatment/prevention of motion sickness and nausea.
15. Several chewing gum formulations containing calcium are available on the market. Adolescents constitute a potential target group for a calcium chewing gum as the calcium intake of young people is often very low. Calcium chewing gum with a pleasant flavour is an attractive and convenient alternative to tablets.
16. Miconazole has also been formulated as chewing gum and these formulations have been used in clinical trails.
17. As Propranolol exhibits first-pass metabolism, a chewing gum formulation was seen as a viable option to obtain buccal absorption.
That was very nice article.
It would be a kind of you to send me the pdf copy of this article