A Comprehensive Review on Medicated Chewing Gum (MCG): A Novel Drug Delivery System

Medicated chewing gum represents a novel and patient-centric approach to drug delivery that has garnered increasing interest in the pharmaceutical industry. This unique dosage form provides a combination of therapeutic efficacy and convenience, making it an appealing alternative to conventional drug delivery methods such as tablets, capsules, and syrups. Unlike traditional oral formulations that require swallowing and digestion, medicated chewing gum is designed to release the active pharmaceutical ingredient during the process of mastication, allowing for absorption through the oral mucosa, gastrointestinal tract, or both. This dual absorption mechanism enhances drug bioavailability and offers potential pharmacokinetic advantages, particularly for drugs susceptible to extensive first-pass metabolism.^1-3 The development of medicated chewing gum has been largely driven by the need for more patient-friendly dosage forms that promote adherence and compliance, particularly among populations that may struggle with swallowing solid oral medications, such as pediatric, geriatric, and dysphagic patients. By offering an easy-to-administer, palatable, and non-invasive method of drug delivery, this system has demonstrated promising applications across various therapeutic categories, including pain management, smoking cessation, oral healthcare, central nervous system disorders, and systemic drug administration. The act of chewing itself may also provide added benefits, such as enhanced cognitive function, improved salivary flow, and mechanical cleaning of the oral cavity, making it a multifunctional delivery platform.^4-5 The formulation of medicated chewing gum is a complex process that involves selecting appropriate ingredients to ensure stability, efficacy, and patient acceptability. A typical formulation comprises a gum base, active pharmaceutical ingredients, sweeteners, flavoring agents, plasticizers, and other excipients that facilitate controlled drug release. The gum base serves as the primary structural component, dictating the texture, elasticity, and mechanical properties of the product. Additionally, the composition of the formulation influences the release kinetics of the drug, which can be tailored for immediate, sustained, or modified release depending on the therapeutic requirement.⁶ One of the most significant advantages of medicated chewing gum is its ability to bypass first-pass metabolism when the drug is absorbed through the buccal mucosa. This mode of absorption not only enhances bioavailability but also ensures a more rapid onset of action, making it particularly suitable for conditions requiring quick symptom relief. Moreover, medicated chewing gum offers a discreet and portable option for drug administration, allowing patients to take their medication without the need for water or additional aids. This feature is especially beneficial for individuals with active lifestyles who require on-the-go medication solutions. Despite its numerous benefits, the development of medicated chewing gum as a drug delivery system presents certain challenges. The physical and chemical stability of the drug within the gum matrix must be carefully evaluated to prevent degradation and ensure consistent dosing. Furthermore, the mechanical properties of the gum, including its chewability and texture, play a crucial role in patient compliance and drug release kinetics. Regulatory considerations also influence the development and commercialization of medicated chewing gum, as variations in chewing habits among individuals may impact the uniformity of drug release and overall therapeutic effectiveness.⁷ This comprehensive review aims to explore the potential of medicated chewing gum as an innovative drug delivery system by examining its formulation strategies, pharmacokinetic properties, therapeutic applications, advantages, limitations, and regulatory landscape. With advancements in pharmaceutical technologies and consumer preferences shifting toward more convenient and enjoyable medication formats, medicated chewing gum represents a promising frontier in drug delivery that warrants further research and development.

Advantages of Medicated Chewing Gum

1. Medicated chewing gum does not require water for administration, making it a convenient option that can be taken anytime and anywhere.
2. This drug delivery system ensures precise dosing, allowing for accurate and consistent medication intake.
3. By stimulating saliva production, medicated chewing gum helps to counteract dry mouth, prevent oral infections such as candidiasis, and reduce the risk of dental caries. Additionally, it aids in teeth whitening by minimizing and preventing stains.
4. The pleasant taste and ease of administration make medicated chewing gum highly acceptable among children, improving adherence to treatment.
5. This formulation bypasses significant first-pass metabolism, leading to enhanced drug bioavailability and improved therapeutic effectiveness.
6. Since the gum is not swallowed, the gastrointestinal tract is less exposed to excipients, reducing the likelihood of irritation or adverse effects associated with conventional oral medications.
7. The direct exposure of the gastric mucosa to high drug concentrations is avoided, thereby lowering the risk of gastric intolerance or irritation.
8. The fraction of the drug that reaches the stomach is gradually conveyed through saliva, ensuring a continuous and prolonged release that extends the duration of action.
9. Treatment can be easily discontinued at any time by simply discarding the chewing gum, providing better control over drug administration.
10. Certain drugs, such as aspirin, dimenhydrinate, and caffeine, demonstrate faster absorption when delivered through medicated chewing gum compared to traditional tablet formulations.
11. By stimulating salivary flow, medicated chewing gum helps maintain oral hygiene and provides a soothing effect for individuals suffering from dry mouth.
12. The increased saliva production induced by medicated chewing gum aids in neutralizing plaque acids that form in the mouth after consuming fermentable carbohydrates, contributing to better dental health.^8-11

Disadvantages of medicated chewing gum

1. Prolonged chewing of medicated gum can lead to discomfort, causing pain in the facial muscles and, in some cases, earache, especially in children.
2. There is a higher risk of overdose with medicated chewing gum compared to chewable tablets or lozenges, as patients may unintentionally chew multiple pieces.
3. The presence of sorbitol as a sweetening agent in medicated chewing gum can cause gastrointestinal issues such as flatulence and diarrhea, particularly in individuals with sorbitol sensitivity.
4. Medicated chewing gum may adhere to dental restorations, including enamel, dentures, and fillings, potentially causing discomfort or damage.
5. Certain additives, such as flavoring agents and cinnamon, can contribute to the development of oral ulcers, while ingredients like licorice may lead to an increase in blood pressure.
6. The use of chlorhexidine in medicated chewing gum is limited to short-term applications due to its unpleasant taste and tendency to stain the teeth and tongue.^8-14

Types of Chewing Gum

Chewing gum can be classified into different types based on its formulation, texture, and method of preparation. Each type requires specific gum base properties to ensure optimal flexibility, stability, and ease of consumption. Below is a detailed explanation of the different types of chewing gum:¹⁵

1. Cut and Wrap Chewing Gum

Cut and wrap chewing gum is designed to endure significant stretching during the manufacturing process. The gum base used in this type must be highly flexible to withstand the cooling process without breaking. Since this variety typically has larger pieces than traditional gum, the formulation is softer. This is achieved by incorporating higher amounts of liquid ingredients such as glucose syrup and sweeteners, which enhance the gum's texture and chewability.^16-17

2. Stick and Tab Chewing Gum

Stick and tab chewing gum is produced using a lamination process, which requires a gum base that is both flexible enough for rolling and firm enough to maintain its shape after curing. Unlike cut and wrap gum, this type contains a lower percentage of gum base. Proper glucose content regulation is essential to ensure the right balance of elasticity and hardness, preventing breakage during bending and ensuring smooth packaging.^18-20

3. Pellet or Pillow Chewing Gum

Pellet or pillow-shaped chewing gum is a popular format that resembles small stick-like pieces. The gum base for this type must be pliable enough to undergo rolling while also being sufficiently firm to harden and retain its shape after the curing and cooling processes. This ensures durability and a pleasant chewing experience.^21-23

Figure 01: Pellets/pillows chewing gum

4. Hollow Ball Chewing Gum

Hollow ball chewing gum, often filled with flavoring agents or liquid centers, requires a gum base with a precise balance of elasticity and plasticity. The base must be strong enough to maintain its spherical structure and prevent leakage of the filling. Additionally, the outer shell should be resilient enough to endure the coating process without cracking or losing its shape.

5. Liquid-Filled Chewing Gum

This variety contains a liquid center encased within the gum. The gum base must have sufficient elasticity to withstand stretching during production while also possessing the plasticity required to be shaped efficiently by the molding dies. Maintaining an optimal gum base percentage is crucial; if the content is too high or too low, the product may lose its structure, resulting in leakage or deformation.²²

6. Gum-Filled Candy

Gum-filled candy consists of a chewing gum center encased in a hard candy shell. The gum base in this type must have a lower viscosity to ensure smooth processing. However, handling can be challenging, as the gum may become too fluid when exposed to the high temperatures used in confectionery manufacturing. Precise control over formulation and processing conditions is necessary to achieve the desired texture and stability.²³

Figure 02: Gum-Filled Candy

7. Compressed Chewing Gum

Compressed chewing gum is formulated as a dry powder that is pressed into solid gum tablets. This type is widely used in pharmaceutical and functional chewing gum applications, where active ingredients such as vitamins, minerals, or medications can be incorporated. The compressible powder allows for controlled release of the active components while maintaining the gum’s chewable consistency.²² Each of these chewing gum varieties is developed using specific formulations to enhance texture, stability, and consumer experience, ensuring that they meet the intended functional and sensory requirements.²³

Figure 03: Compressed chewing gum

Components Required for Medicated Chewing Gum Formulation:^24-27

Table 01: Water-Insoluble Gum Base Components in Medicated Chewing Gum

The manufacturing process of medicated chewing gum involves various techniques, each tailored to achieve specific texture, taste, and drug-release characteristics. ^28-30

1. Fusion method
2. Cooling, grinding, and tableting method
3. Direct compression process

1. Fusion method

The fusion method is one of the most commonly used techniques. The process begins by melting and softening the gum base at approximately 60°C in a kettle mixer. The softened gum base is then blended with ingredients such as sugar, glycerin, sweeteners, and taste-masking agents. To preserve the volatile nature of flavoring agents, they are incorporated at a lower temperature of around 40°C. Once the mixing process is complete, the gum undergoes cooling and rolling, after which it is cut into the desired shapes and sizes. For coated gum tablets, a coating agent is sprayed over the pieces to create a smooth and uniform surface.

An alternative variation of the fusion method involves a slightly different sequence of ingredient addition. In this approach, a mixer, such as a sigma blade mixer, is prepared. If the formulation includes sugar, corn syrup is added first, followed by powdered sugar, which may include sucrose, dextrose, fructose, or corn syrup solids. To enhance the texture and cohesiveness, plasticizers such as glycerin are introduced. Additional components, including fillers, colorants, and flavoring agents, are incorporated to achieve the desired properties. However, flavorants are typically added at the final stage to prevent the loss of volatile compounds. The composition of the gum base varies depending on the formulation, with powdered sugar often making up the highest proportion. The mixing process is facilitated by mechanical forces such as compression and shear, and in the absence of heat, additional power is required. The mixing phase generally lasts about eight minutes to ensure homogeneity. Another approach involves adding sugar gradually until all other components have been incorporated. The prepared gum base particles are then introduced into the mixture, and mixing continues for an additional 10–20 minutes. Unlike the traditional fusion method, this technique first forms the sweetener matrix before incorporating the gum base pellets. This modification reduces the likelihood of sugar lump formation, enhancing the final product's quality.^21-23

2. Cooling, grinding, and tableting method

Another widely used method in chewing gum manufacturing is the cooling, grinding, and tableting method. In this technique, the gum base is blended with sweeteners, corn syrups, starches, flavoring agents, and colorants. The mixture is then cooled rapidly using a freezer apparatus or a coolant such as carbon dioxide until it reaches a temperature below -15°C. At this point, the solidified mass is crushed and ground into fine particles using a cutter or grinding apparatus. The ground particles are then heated to a temperature that allows them to adhere to one another, forming a uniform bulk with a consistent texture and low specific gravity. If the particles do not self-adhere, low pressure may be applied before warming them to room temperature to facilitate cohesion. The cooling and grinding processes can also be combined by cooling the grinding apparatus itself. Once the grinding step is complete, any residual coolant is allowed to evaporate. The minute particles may be coated with edible substances or pre-mixed with powdered materials to enhance stability and taste. For tableting purposes, compression punches are used, and an anti-adherent agent is applied to prevent sticking to the punch surfaces.^23-24

3. Direct Compression Method

A more advanced method, known as direct compression, is gaining popularity in the production of chewing gum tablets. This technique utilizes high-speed compression machinery to create rapidly dissociable gum tablets. When chewed, the tablet disintegrates within a few seconds before the particles adhere together, forming a uniform mass. The formulation includes a granulating agent, such as sorbitol, which also serves as a sweetener. Lubricants like magnesium stearate, talc, stearic acid, hydrogenated vegetable oils, and sodium stearyl fumarate are added before tableting to improve processing efficiency. The process begins with dry mixing of the gum base, granulating agent, and processing materials. Active ingredients, sweeteners, and other necessary excipients are then incorporated in their free-flowing forms before direct compression into tablets. Throughout the process, the temperature must remain below the melting point of the gum base to maintain structural integrity. After achieving a uniform mass, the temperature is lowered to facilitate the addition of other ingredients. The compressed chewing gum tablet is designed for controlled drug release into the oral cavity. Upon chewing, the active ingredient is released within 2–10 chews, ensuring rapid absorption. This method offers several advantages over traditional techniques, including faster drug release, improved absorption, and high content uniformity. Furthermore, bi-layered compressed chewing gum formulations are now being explored to enhance drug delivery efficiency, providing a novel approach for administering pharmaceutical compounds through medicated gum.^23-24

Evaluation of Medicated Chewing Gum (MCG)^{23-24, 25-39}

Organoleptic Properties

The organoleptic evaluation of the medicated chewing gum (MCG) involves assessing its physical characteristics, including color, odor, surface texture, and overall appearance. These parameters provide an initial qualitative insight into the formulation’s acceptability and stability. The color and texture should be uniform, while the odor should be characteristic of the ingredients used, ensuring that no undesirable changes have occurred due to formulation instability or degradation.

Stickiness Evaluation

To assess the stickiness of the formulated medicated chewing gum base, a specific procedure was followed. The gum was placed on a plain surface, and a mass of 250 grams was hammered on it continuously for a period of 10 minutes. The hammering was conducted at intervals of 30 minutes to ensure uniform application of force. Observations indicated that none of the batches exhibited stickiness, as the gum did not adhere to the hammer or the surface. This characteristic is crucial in ensuring ease of handling, packaging, and patient compliance.

Plasticity and Hardness Measurement

The plasticity and hardness of the chewing gum were evaluated using the Monsanto hardness tester. This instrument is commonly used to determine the mechanical strength of pharmaceutical formulations. The hardness of the gum was measured, and both the average value and standard deviation were calculated. Adequate hardness is essential to maintain the structural integrity of the gum while ensuring that it remains chewable and palatable.

Weight Variation Test

To ensure uniformity in weight, a weight variation test was conducted on 20 individual chewing gum samples from each formulation. Each sample was weighed separately using an electronic balance, and the average weight was calculated. The individual weights were then compared with the average value to determine the degree of variation. This test is essential for ensuring consistency in drug dosage and uniformity in batch production.

Friability Test

Friability testing is conducted to evaluate the resistance of the chewing gum to mechanical stress, particularly during handling and transportation. This parameter is crucial as excessive friability may lead to crumbling, affecting drug content and patient compliance. The test was carried out using a Roche friabilator, which consists of a rotating disc with a diameter of 12 inches, operating at a speed of 100 revolutions per minute (rpm). Ten units of the gum formulation were placed in the disc and subjected to 100 revolutions at 25 rpm.  For the formulation to pass the friability test, the F% must be less than 1%. This ensures the stability of the gum during storage and handling.

Drug Content Analysis

The drug content in the medicated chewing gum was determined by manually dividing the gum into smaller pieces and transferring them into a separating funnel containing 10 mL of phosphate buffer. The mixture was shaken for 10 to 15 minutes to facilitate the dispersion of the chewing mass. To ensure complete dissolution of the drug, an additional 50 mL of phosphate buffer was added, and the solution was further shaken for another 15 minutes. Afterward, the funnel was kept undisturbed for 15 minutes to allow phase separation. The aqueous phase was collected and filtered using Whatman filter paper. The filtrate was appropriately diluted and analyzed using a UV spectrophotometer to quantify the drug content, ensuring accurate dosage delivery.

In-Vitro Drug Release Study

The in-vitro drug release study is performed to assess the dissolution rate of the active pharmaceutical ingredient from the medicated chewing gum. This is achieved through a mechanical kneading process that simulates the chewing mechanism.

Apparatus I: Chewing Simulation Apparatus

The chewing apparatus consists of several components designed to replicate the chewing action:

• One central chewing chamber
• One vertical piston
• Two horizontal pistons equipped with O-rings and sealing rings

The chewing chamber itself is made up of four parts:

1. A central chamber
2. A funnel
3. Two guides with bushes

The funnel and guides are securely attached to the central chamber. The horizontal pistons artificially chew the gum, while the vertical piston ensures that the gum remains positioned correctly throughout the process. The chewing cycle is well-defined, with each horizontal piston moving between its outermost and innermost positions, while the vertical piston reciprocates to maintain proper alignment.

The movement specifications for the apparatus include:

• Horizontal piston stroke: 25 mm
• Maximum distance between horizontal pistons: 50 mm
• Minimum distance between horizontal pistons: 0.1 mm to 1.0 mm
• Vertical piston stroke: 22 mm

The precise control of piston movement ensures uniform mastication, closely mimicking natural chewing action. If necessary, the apparatus can be modified to allow the horizontal pistons to rotate in opposite directions at the end of each chewing cycle to maximize drug release.^21-23

An alternative chewing apparatus, developed by Wennergren, offers a different approach to simulating the mastication process. In this setup, the lower surface of the apparatus moves in a reciprocating manner, while the upper surface provides a shearing or twisting action. This dual mechanism not only mimics chewing but also ensures adequate agitation of the dissolution medium, enhancing drug release. The lower surface has a slightly angled brim (45°), which forms a shallow bowl-like structure, preventing the gum from slipping during mastication.

Both apparatuses are designed using chemically inert materials to prevent adsorption or interference with the dissolution medium, ensuring accurate and reproducible results.^21-24

Stability studies were conducted to evaluate the long-term consistency and integrity of the formulated medicated chewing gum. These studies followed the guidelines set by the International Council for Harmonisation (ICH), with necessary modifications. The chewing gum formulations were stored under different temperature conditions, including: 30 ± 2°C, 40 ± 2°C and 45 ± 2°C. The stability tests were conducted over a period of 45 days. During this period, the samples were evaluated for various parameters, including consistency, color, odor, and drug content. Any significant changes in these characteristics would indicate instability, thereby affecting the overall efficacy and shelf life of the formulation. By conducting these evaluations, the formulated medicated chewing gum can be assessed for its quality, safety, and effectiveness in delivering the intended therapeutic benefits.

Applications of Medicated Chewing Gum^{23, 31-39}

Medicated chewing gum (MCG) has emerged as a novel and effective drug delivery system that offers several advantages, including controlled drug release, improved patient compliance, and ease of administration. The primary applications of MCGs can be categorized into two major therapeutic areas: local therapy and systemic therapy.

Local Therapy

One of the most significant applications of medicated chewing gum is in the prevention and treatment of oral diseases. These formulations allow the controlled release of active pharmaceutical ingredients (APIs) directly into the oral cavity, ensuring prolonged local effects against dental caries, infections, and other oral health conditions. A key benefit of MCGs in local therapy is their ability to increase plaque pH, which plays a crucial role in preventing dental caries. Since acidic plaque conditions contribute to enamel erosion and cavity formation, sugar-free chewing gums are commonly recommended after meals as part of caries prevention programs.

Treatment and Prevention of Dental Caries

Medicated chewing gums serve as an effective tool for targeting dental caries by allowing prolonged contact of active substances with the teeth and oral mucosa. Fluoride-containing chewing gum is widely used to prevent dental caries in children, as fluoride strengthens enamel and reduces demineralization. Additionally, chlorhexidine-containing chewing gum is an effective option for treating various oral infections, including gingivitis and periodontitis. Unlike conventional chlorhexidine mouth rinses, which often cause tooth staining, chlorhexidine chewing gum provides antimicrobial benefits with minimal discoloration. Furthermore, medicated chewing gums can help mask the bitter taste of certain drugs, enhancing patient acceptability. Kolahi and Abrishami (2013) developed a mutanase-containing chewing gum that was found to effectively prevent dental plaque formation and reduce the risk of dental caries in experimental animal models. This research highlights the potential of innovative chewing gum formulations in improving oral health.

Systemic Therapy

Apart from local therapy, medicated chewing gum is widely utilized for systemic drug delivery through the buccal mucosa. This route of administration offers numerous advantages, including rapid drug absorption, easy administration without the need for water, reduced gastrointestinal side effects, and improved patient adherence. MCGs have been explored for a variety of systemic therapeutic applications, including pain management, smoking cessation, obesity treatment, and other medical conditions.

Pain Management

Medicated chewing gum formulations containing nonsteroidal anti-inflammatory drugs (NSAIDs) have been developed to provide relief from minor pains, headaches, and muscular aches. One of the earliest available medical chewing gums, Aspergum®, contains acetylsalicylic acid (aspirin) and offers an alternative to conventional NSAID tablets. By allowing direct absorption through the oral mucosa, this formulation bypasses first-pass metabolism and may reduce the risk of gastrointestinal irritation associated with oral NSAIDs.

Smoking Cessation

Nicotine chewing gum is a well-established aid for smoking cessation. Various formulations containing nicotine, silver acetate, and lobeline have been clinically tested for their effectiveness in reducing nicotine cravings and withdrawal symptoms. Aslani and Rafiei (2012) developed a nicotine-containing chewing gum using the direct compression technique, demonstrating that the optimized formulation had excellent chewing properties, a pleasant taste, and high acceptability among smokers. This method provides a convenient way to manage nicotine dependence while helping individuals gradually reduce their smoking habit.

Obesity Management

Medicated chewing gums have also been explored as a potential aid for weight management and obesity treatment. Certain active substances, such as chromium, guarana, and caffeine, have been incorporated into chewing gum formulations to promote weight loss and appetite suppression. Caffeine and guarana have been shown to increase metabolic rate, stimulate fat breakdown (lipolysis), and reduce hunger sensations. Aslani and Jalilian (2012) developed a caffeine-containing chewing gum that was found to increase alertness and reduce fatigue, highlighting its potential as an energy booster. Chromium has also been included in MCG formulations due to its role in improving blood glucose balance, which can contribute to weight management.

Other Therapeutic Applications

In addition to its primary uses in oral health, pain relief, smoking cessation, and obesity management, medicated chewing gum has been explored for various other therapeutic indications. It has been found beneficial in conditions such as xerostomia (dry mouth), allergies, motion sickness, acidity, colds, coughs, diabetes, and anxiety. Chewing gum is known to stimulate salivary secretion, which can be advantageous for individuals suffering from dry mouth. Pilocarpine-containing chewing gum formulations have been developed to increase saliva production, improving oral hydration and comfort. Additionally, antacid-containing chewing gums can help reduce gastric acidity and postprandial reflux by neutralizing stomach acid. The buffering action of stimulated saliva further contributes to the neutralization of gastric fluids, providing relief from acid-related discomfort. Caffeine-containing chewing gum has been shown to have cognitive-enhancing properties, with studies suggesting a positive effect on memory, focus, and mental alertness. Furthermore, chewing gums containing active ingredients such as dimenhydrinate, scopolamine, and dolasetron have been used for the prevention and treatment of motion sickness, nausea, and diarrhea. These formulations offer a non-invasive and convenient alternative to traditional oral medications, particularly in situations where swallowing tablets or capsules may be challenging, such as during travel or chemotherapy-induced nausea.^21-23