Revolutionizing Oral Health: A Comprehensive Update on Medicated Chewing Gum Benefits

Shah Shoaib R.¹, Patil Pratik D.², Dr. Gangurde Avinash B.², Sufiyan Akhtar³,

Sayyed Shoaib C².

1.Gangamai Institute of Pharmacy Nagaon, Dhule Maharashtra 4240005.

2. K.B.H.S.S. Trust’s Institute of Pharmacy, Malegaon, Maharashtra 423105.

3. SES Institute of Pharmacy Navalnagar dhule, Maharashtra 424318.

*Correspondence: shoeb12911@gmail.com

INTRODUCTION

Gum chewing is a portable delivery of drugs method. It is beneficial approach to administer medications either topically or through the oral cavity systemically. As a method of medicine delivery, medicated chewing gum has become more and more popular over time. The base of MCG is primarily made by gums which are designed to be chew rather than swallow, allowing for a slow, consistent release of the medicine inside. It is a method of delivering Active Pharmaceutical Ingredient that consists of a base made of masticator gum that has pharmacological active ingredients and is indented to either mouth disease therapy or systemic absorption through the oral mucosa. Additionally, the buccal medication delivery method has significant benefits in that it bypasses first pass hepatic metabolism and provides direct access to the general circulation(Zieschang et al., 2018). Medicated chewing gums are consumed by eating through mouth additionally, the preferred method of medicine delivery is oral method for patients and healthcare professionals due to the many benefits it provides, chewing gums have gained recognition in recent years as a safe and effective method of oral mucosal drug delivery. When compared to oral liquids and tablets, chewing gum may be the preferred drug delivery method for children in particular. It is possible to use MCG to treat systemic conditions as well as local oral cavity diseases.

Gum is regarded as a legitimate drug delivery method because chewing it the active substance is released. In MCG’s demonstrated superior means of distribution to nutrition and medicines. Chewing gum is mixed of natural and artificial resins and gums that have been sweetened with added sweeteners, corn syrup, and sugar (Wen et al., 2017). Also contains flavouring, colouring, bulking, softening, antioxidants, and glidants. Medicated chewing gums are made using a variety of techniques, including direct compression, conventional, traditional, cooling, and grinding. The remaining amount of a medicated gum is meant to be discarded after being chewed for the necessary amount of time to deliver the dose, the drug and ingredient found in the gum product is released during chewing and absorbed through the mucosa of the mouth or ingested, reaching the stomach to be absorbed by the digestive system. “State of Maine pure spruce gum" was the first chewing gum to be offered commercially in the United States. which debuted in 1948. In 1869, Field was granted the first patent. Gum was never commercialized regardless of being intended as dentifrices (Thivya et al., 2021). The first medicinal chewing gum, "As per gum," was released in 1928. This acetyl salicylic acid-containing chewing gum is still readily accessible. For people who experience motion sickness, chewing gum with dimenhydrinate is commercially available. However, it wasn't until 1978 that nicotine chewing gum became widely accessible that it was recognised as a trustworthy drug delivery method.

Additionally, it gains from the perks that come with chewing gum, such as enhanced focus and attention, stress alleviation, and weight management (Soni et al., 2022). After eating a medicinal chewing gum for the prescribed amount of time, the remaining bulk is intended to be thrown away after requisite amount of time to provide the dose. In comparison to tablets or liquid formulations, this medication delivery technology offers advantages such a pleasant flavour, a high bioavailability, rapid onset of action improved patient compliance, readiness as a use, and fewer adverse effects. The solubility of a medicine in water determines how quickly it will be released from MCG. While possible that delay the rapid and complete release of water soluble compounds from medicated chewing gum to create a delayed release profile, this is not always possible. Few medications make good candidates for inclusion in gum formulations for the purpose of systemic distribution. The following oral dose forms provide the medication towards intended areas for oral cavity medication delivery, either local or systemic (Solanki & Chandra, 2018).

DEFINITION:

A solid single-dose preparation known as a chewing gum with medicine is designed being chewed for a specific time in order to provide the drug's active pharmaceutical ingredient. It can also be utilized for oral mucosa-mediated systemic absorption or for local therapy of mouth ailments. The medication product is designed with an indentation that medicament chewed to predetermined amount of time before the water insoluble base is thrown away (Shete et al., 2015).

THE ADVANTAGES OF CHEWING GUM:

Chewing gum with medications has many benefits.

Gum can be chewed anywhere and at any time without the need for water.

Product stability is good because the medicinal chemicals that have been integrated are shielded from oxygen, light, and water (Sahu et al., 2023).

Compatible with people who have trouble swallowing.

Fantastic for use in acute medicine.

Helps treat dry mouth and guards against cavities and candidiasis.

Swift and quick start to activity.

A high bioavailability.

A tasty flavour.

Enhances medication bioavailability by avoiding first-pass metabolism.

Able can be used.

Less negative effects.

Regional impact.

Stress reduction with improved concentration and focus.

Action's duration lengthens.

Stimulates the mouth's natural flow of saliva.

Since gum doesn't upset the stomach, GIT is less affected by the side outcomes of excipients.

Makes teeth become whiter by minimizing the stains (S. et al., 2023).

DISADVANTAGES OF CHWING GUM:

The in the MCG formulation, sorbitol may have unwanted causes including flatulence and diarrhoea.

Gum chewing is demonstrated to attach to fillings and dentures made of enamel in a challenging way.

Long-term gum chewing can cause characters to develop pan in their facial muscles and ears (Poulsen et al., 2022).

CHARACTERISTICS OF CHEWING GUM:

Gum is a smooth, cohesive material, which is meant being chewed rather than ingested.

Modern chewing gum is made comprised of a gum base, sweeteners, softeners, plasticizers, flavours, colours, and frequently a hard or powdered polyol coating.

Its polymer plasticizer and resin components' physical chemical properties, which also contribute to its elastic plastic, sticky, and chewy attributes, giving it a texture that is reminiscent of rubber (Patel et al., 2017).

POLYMERS USED IN CHEWING GUM PREPARATION:

When making chewing gum, a variety of polymers and cross-linkers are employed.

Polymers:

cyclodextrins and their derivatives, such as poly isoprene and poly butadiene, methyl B cyclodextrins, and hydroxypropylcyclodextrins, are hyperlinked polystyrenes.

Co-polymers:

In addition to combinations of these substances, polyvinyl alcohol, polyvinyl acetate, copolymers of styrene and butadiene, vinyl acetate and vinyl laureate, copolymers of lactic acid, polyhydroxyalkonates, plasticized ethyl cellulose, and polyvinyl acetate phthalate are also acceptable (Paradkar et al., 2016).

Cross linkers:

Cross-linked polymethylmethacrylate and polyvinylpyrrolidone.

ESSENTIAL INGREDIENTS IN MEDICATED CHEWING GUM:

Pharmaceutical active component (API):

The following requirements ought to be met by the active medicinal components. Any unpleasant taste in the medication should be avoided since it may reduce patient compliance.

The drug's particle size should be kept below 100 m to prevent an unpleasant gritty feeling during chewing.

Drug physicochemical characteristics like a lot of saliva and solubility independent of pH.

The patient's circumstances such those that are harmless to the salivary ducts and oromucosa, not carcinogenic and shouldn't result in tooth decay or influence salivary flow rate should not cause tooth decay (Nowosielska et al., 2021).

Gum base:

It serves as a base for the soluble and edible ingredients in chewing gum (glucose, sugar, polyols, and flavours). In addition, there are often divided into the following:

Elastomers:

It gives the chewing gum cohesiveness, gummy texture, and elasticity. Natural gums or latex gums likelechicaspi, perillo, chicle, and jelutongare examples of natural elastomers. It uses synthetic elastomers such butyl-1-rubber, polyisobutylene, and polyethylene acetate.

Plasticizers:

These are employed to control the product's cohesion. Again, these are separated natural and artificial plasticizers. The rosin esters pentaerythritol esters of resin, glycerol esters of polymerized esters, glycerol esters of partially dimerized rosin, and glycerol esters of partially hydrogenated rosin are examples of natural plasticizers. D-limonene and/or pinene-based terpene resins are among the synthetic plasticizers (Maslii et al., 2020).

Resins:

They fulfil two purposes. They both help maintain an equilibrium between the qualities elastic and plastic properties, one as a chewing agent and the other as a glue between fillers and elastomers. Resin which is natural include pine resin-derived glycerol esters. Polyvinyl acetate, aartificial resin, may be used. It lessens the gum's propensity to stick to the teeth (detackifier) and break apart while being chewed on. Its stability is good, it has a light flavour, and its molecular weight varies (Mansoori et al., 2022).

Fats and emulsifiers:

Which areutilizedto make the mixture softer and provide the necessary mouth feel and chewing consistency. Emulsifiers encourage saliva to enter the chewing gum when it is being masticated. Examples include partially solidified animal and vegetable fats, monoglycerides, and diglycerides.Examples of softeners include lecithin, tallow, glycerin, mono/di/tri-glycerides, and palmitic acid (Lieberman et al., 1989).

Fillers or Textures:

They provide the gum base the proper texture and increase a gum lump's suitable size by using a tiny amount of medication. Common fillers include magnesium and calcium carbonate, powdered limestone, Clay, alumina, talc, titanium oxide, magnesium and aluminium silicate, and mono, di, and tricalcium phosphate.

Antioxidants:

Are used to prevent oxidation of the flavours and gum base. Ascorbic acid, butylhydroxytoluene, and tocopherol have all been used (LALL DIPESH et al., 2020).

Sweetening agents:

a. Water-mixable sweetener:

The partially hydrolyzed starch and invert sugars glucose, mannose, galactose, fructose, sucrose, and maltose, monellin, steviosides, glycyrrhizin, and dihyrochalconesalcohols like mannitol and sorbitol, as well as starch hydrolates.

b. Water-mixable, artificial sweeteners:

Salts of soluble saccharin, such as Sodium or calcium salts of saccharin and cyclamate salts.

c. Sweeteners made from dipeptides:

Aspartame, the 5-dihydro-L Phenylalanine-L (cyclohexen) alanine, L-Aspartyl-L 2,5-dihydrophenylglycine, and L-aspartyl-2 all have methyl esters. Are a few examples of sweeteners created from dipeptides (Lakshmi et al., 2014).

d. sweeteners made from proteins:

like Thaumaoccous Danielelli (Thaumatin I and II) Generally, a sufficient the quantity of sweetener used to achieve the required sweetness level; this amount varies based on the sweetener selected and ranges from 0.0025 to 90% of the gum content by weight (Kumar et al., 2022).

flavoring agents:

Essential oils, fruit essences, peppermint, spearmint, clove, and wintergreen oils are just a few of the flavouring ingredients used to enhance chewing gum flavour. You can also utilise artificial flavourings.

Anti –caking agent:

Before grinding, mix of chewing gum and solid carbon dioxide can be combined with a substance that prevents caking, such precipitated silicon dioxide. This aids in preventing the subsequent grinding of chewing gum particles from clumping together (Khatiwara et al., 2021).

Antioxidants:

Antioxidants like propyl gallate, butylated hydroxytoluene, and butylated hydroxy anisole, as well as combinations of these, may be used.

Grinding agents:

To keep the gum from sticking to the grinder, add 2 to 8 percent weight-weight of a grinding aid, such as maltodextrin, an alkaline metal phosphate, or an alkaline earth metal phosphate. However, due to their high alkalinity and incompatibility with therapeutic treatments that are acidic and ionizable, the practical usage of these compounds is constrained. Additionally, they frequently stay in the final chewing gum composition, which could be problematic from a therapeutic and safety standpoint (Kaushik & Kaushik, 2020).

VARIETIES OF CHEWING GUM:

Gum for chewing comes in a range of flavours, forms, and dimensions. Gum is available in a range of sizes and shapes; however, little sticks or wads are the most common. Basically, sweeteners, flavours, and food colouring are combined with a water-soluble phase to create chewing gum.

Basic varieties of chewing gum available now are e

Bubble gum:

Due of its ability to form films, bubble gum has the ability to blow bubbles.

Sugar-free gum:

Artificial sweeteners are used in sugar-free gum to replace sugar as the flavouring.

Center-filled gum:

The centre of center-filled gum is a soft mass that is typically filled with a pleasant liquid (Karki & Yadav, 2010).

Dragee gum:

The most widely used type of chewing gum is called Dragee gum, which comes in the form of coated pillows that are frequently packaged in blister made packaging.

Medicated type gum:

Medicated type gum is a type of chewable gum designed to speed up the absorption of medications compared to pills. Their names are given based on their shapes:

Sticky gum:

Sticky gum is a flat, thin slab of gum that is typically shaped like a rectangle.

Ball like gum:

Gum has a ball-like appearance. It is one of the most popular gums.

Ribbon like gum:

Similar to sticky and ribbon like gum is longer and in a cylindrical container, coiling up. The user removes a fragment of the desired size from the container.

Wrap gum:

Depending on the machine that wraps it, Cut and wrap gum are typical in shape chunky, cubical, or cylindrical in form.

Tube like gum:

The bubble gum within the tube, sometimes known as spaghetti gum or tube gum, is incredibly soft (Kaushik & Kaushik, 2020).

MANUFACTURING PROCESSES:

Although other techniques can be used to create MCGs, They are generally divided in three kinds:

Traditional/Fusion Technique

Method of cooling, grinding, and tabletting

Method of direct compression

Traditional/Fusion Technique

Gum base components are melted or softened, then added to an industrial mixer with syrups, sweeteners, and active substances, and another excipient at predetermined intervals. After passing through several rollers, the gum is then formed into a thin, flat ribbon. To make the gum less sticky and to make it taste better, a thin layer of sugar substitutes or finely powdered sugar is added. Throughout this procedure. These gum is chilled for up to two days in an area that is carefully controlled. This enables the gum to properly set. As shown in Figure 1, these gum is finally chopped to proper shape and chilled at a humidity and temperature that are carefully controlled (Karade et al., 2024).

Limitations:

The applicability of this approach for thermo labile pharmaceuticals is restricted by the elevated temperature utilised in melting.

It is challenging to manage the accuracy and homogeneity of a medicine dose while melting and blending a quantity of extremely viscous gum.

Lack of dose form with a particular weight, size, or form.

Technical equipment’s doesn’t readily adapt to the strict manufacturing requirements needed to produce pharmaceutical items.

Because of moisture level, such components of chewing gum are challenging to shape into chewable gum tablets (2-8 percent). If such a combination was attempted to ground and tablet, it would clog the grinder, adhere to the punches and blades, and be difficult to compress (Cocco et al., 2020).

Method of cooling, grinding, and tableting:

This technique was created in an effort to reduce moisture content and address the issues with current methods the composition changes after cooling the MCG foundation. The composition changes after cooling the MCG foundation, becomes sufficiently brittle and wouldn’t stick to the grinding device during the subsequent grinding process. By monitoring the characteristics of the cooled chewing gum composition, it is simple to estimate empirically the proper temperature needed for cooling, which is partly based on how the MCG is composed. The chilled mixture typically has a temperature of -15 ℃ or less solid carbon dioxide is preferred over other because it can reach temperatures as low as -78.5℃, liquid nitrogen and hydrocarbon slush are excellent coolants. Sublimes easily when heated, it is not absorbed by the nature of chewing gum, has no negative interactions with processing equipment, and leaves no residue that might be unwelcome or potentially dangerous. The chilled compound is next crushed or ground to create tiny pieces of the finished ground component. Alternately, the stages involved in cooling the composition for chewablegum can consolidated into one step (Bhoi et al., 2014). The chewing gum composition can be pre-cooled before cooling to the refrigerator temperature for more efficient cooling. For instance, the grinding machine itself can be cooled by being in contact with a coolant or by being enclosed in a cooling jacket of liquid nitrogen or another cold liquid. The chewing gum composition can be pre-cooled before cooling to the refrigerator temperature for more efficient cooling. For instance, the grinding machine itself can be cooled by being in contact with a coolant or by being enclosed in a cooling jacket of liquid nitrogen or another cold liquid. In the first phase, a mill grinder may occasionally grind a combination of gum content, both precipitated silica and solid carbon dioxide. In the second phase, the composition is further ground after being mixed with additional solid carbon dioxide and silica. The ingredients in chewing gum is advantageously kept at a very less temperature by this two-step grinding procedure.

The method of grinding is made more effective by the presence of carbon dioxide in solid form. By addition more carbon dioxide or crystalline silica at each phase, at the process can be multiplied. To help with cooling, grinding, and for chewing gum to have the desired properties, the composition can include particular additions. Anti-caking chemicals and the usage of grinding agent 25 are a few of these (Aslani & Rafiei, 2012). The powder can be mixed once the coolant has been removed from it. In a high-shear mixer or a suitable blender with additional substances that work well with the components of the chewing gum base, such as binders, lubricants, coating agents, and sweeteners. An alternative is to utilise a fluidized bed processor (FBP). It is advantageous to employ FBP because it partially transforms to combine with anti-adherents like talc, the powder is transformed into granules and coated to coat the powder particles or granules. The combination may inspected and prepared for compression after being combined in an octagonal blender.

Limits:

It necessitates equipment different from conventional tableting tools and meticulous humidity monitoring required when tableting is being done (Banakar et al., 2022).

Method of direct compression:

If there is a chewing gum excipient that is directly compressible, the manufacturing process can be sped up. By using these, the drawbacks of melting and freezing can be avoided. Pharmagum, a system created, it is a combination of Sugar, polyols, and base of gum. S Pharmagum is predominantly made of sorbitol and base of gum. Mannitol, Isomalt, and gum base make up Pharmagum M. These are immediately compressible free-following powders. It is produced in accordance with CGMP guidelines and meets both FDA and Codex requirements for food chemicals, making it "Generally recognised as safe" (GRAS).

Aspects of formulation:

Drugs that are not very water soluble are made more aqueously soluble using the cyclodextrin complexation or solubilization process.

Increased softer and emulsifier content in the base of gum speeds up mixing, where hardened gum may slow it down.

A sustained medication administration system is made possible by a stable system of active lipophilic substances attached to cat ion exchange resin.

The techniques for modifying and controlling the release of the active ingredient are microencapsulation or agglomerations (Aslani & Rostami, 2015).

FACTORS AFFECTING ACTIVE INGREDIENT RELEASE:

The releasing pharmaceuticals in chewing gum has demonstrated to be influenced by a number of circumstances. The primary Determinants include chewing rate, time, the mixing of the drug in water and the makeup of the chewing gum components.

Contact Time and rate:

A study was conducted to ascertain the duration of chewing time since the duration of MCG's interaction with the mouth mucosa determines whether it has a local or systemic effect.  Each piece of gum took an average of 30 to 35 minutes to chew. The amount of medication released is also influenced by how quickly an individual chews gum. There are roughly 60 chews every minute on average (Akbal et al., 2017).

Inter individual variability:

Everybody chews differently, which can impact how much and how often MCG releases its medication. The European Pharmacopeia's in-vitro study recommends 60 chewing cycles per minute for the optimal release of the active component.

Solubility of the drug:

The solubility in lipid medications released into the base of gum first, and then slowly released, whereas saliva mixable components are released instantly within a few minutes. In general, the release of a medication that is fluid soluble (solubility more than 1:10) occurs approximately a 75 percent or higher during the initial five minutes of chewing, and 90 percent or more during the following 16 min of chewing at a chew rate of 60 per minute even if the gum is chewed for 30 minutes, the release of a medicine that is only marginally water-soluble can only be anticipated to be minimal (less than 5 percent). When chewing gum for 10 minutes, drugs with a solubility of 1:10 to 1:300 shows a release of up to 60%, and 50% to 90% when chewing for 15 minutes.

Formulation factors:

Changes in the making of the chewable gum's hydrophilic/lipophilic balance affect how the base mass of the gum affects drug release. Changing the amount of gum base is the simplest way to accomplish this. The formulation will become more lipophilic when the gum base is increased, which will slow the release of a certain active ingredient. Though it’s theoretically potential to produce with very low gum base concentrations, doing so would result in inadequate chewing characteristics, might not commercially effective formulation. It is significantly more efficient to vary the release qualities by incorporating solubilizers into the formulation rather than altering the gum base content. By using this technique, even highly insoluble compounds, such as Nystatine, can be released from the chewing gum.

CONCLUSION:

"In conclusion, medicated chewing gum has emerged as a revolutionary innovation in the field of oral health, offering a convenient and effective means of delivering therapeutic benefits to patients. By leveraging the unique properties of the buccal mucosa, medicated chewing gums can release active substances that target various oral health concerns, including dental caries, smoking cessation, and fungal infections. Moreover, the non-invasive and water-free administration of these gums promotes good compliance and patient convenience, making them an ideal option for patients with swallowing difficulties or those who require acute medication. As the most recent technique, MCG, continues to advance and expand its applications in drugs, over-the-counter medications, and nutritional supplements, it is clear that medicated chewing gum has the potential to transform the way we approach oral health management. By synthesizing the current evidence and identifying the therapeutic advantages of gum chewing, this systematic review provides a comprehensive update on the benefits of medicated chewing gum, highlighting its potential to revolutionize the way we prevent and treat oral health issues.

REFERENCES:

1.       Akbal, O., Cevher, E., & Araman, A. O. (2017). The development and in vitro evaluation of benzydamine hydrochloride medicated chewing gum formulations. Istanbul Journal of Pharmacy, 47(2), 45–51. https://doi.org/10.5152/istanbuljpharm.2017.007

2.       Aslani, A., & Rafiei, S. (2012). Design, formulation and evaluation of nicotine chewing gum. Advanced Biomedical Research, 1(1), 57. https://doi.org/10.4103/2277-9175.100175

3.       Aslani, A., & Rostami, F. (2015). Medicated chewing gum, a novel drug delivery system. In Journal of Research in Medical Sciences (p. 403).

4.       Banakar, M., Moayedi, S., Shamsoddin, E., Vahedi, Z., Banakar, M. H., Mousavi, S. M., Rokaya, D., & Bagheri Lankarani, K. (2022). Chewing Gums as a Drug Delivery Approach for Oral Health. International Journal of Dentistry, 2022. https://doi.org/10.1155/2022/9430988

5.       Bhoi, G. S., Aloorkar, N. H., Shinde, N. G., & Osmani, R. M. (2014). INDO AMERICAN JOURNAL OF PHARMACEUTICAL RESEARCH FORMULATION AND EVALUATION OF MEDICATED CHEWING GUM CONTAINING CHLORPHENIRAMINE MALEATE. Indo American Journal of Pharmaceutical Research, 2014(03), 4.

6.       Cocco, F., Cagetti, M. G., Majdub, O., & Campus, G. (2020). Concentration in saliva and antibacterial effect of Xylitol chewing gum: In vivo and in vitro study. Applied Sciences (Switzerland), 10(8). https://doi.org/10.3390/APP10082900

7.       Karade, P. G., Jadhav (Mali), S., & Shah, R. R. (2024). Formulation Development of Medicated Chewing Gum by Direct Compression utilizing the SeDeM Diagram Expert System. Journal of Drug Delivery and Therapeutics, 14(4), 59–68. https://doi.org/10.22270/jddt.v14i4.6545

8.       Karki, R., & Yadav, A. (2010). Formulation of medicated chewing gum of ondansetron hydrochloride and its pharmacokinetic evaluations. www.ijpsr.com

9.       Kaushik, P., & Kaushik, D. (2020). Medicated Chewing Gums: Recent Patents and Patented Technology Platforms. Recent Patents on Drug Delivery & Formulation, 13(3), 184–191. https://doi.org/10.2174/1872211313666191010093148

10.   Khatiwara, D., Ranabhat, P., Paul, M., & Bagchi, A. (2021). An emerging technique of medicated chewing gum in drug delivery system: A review. Journal of Applied Pharmaceutical Research, 9(4), 1–8. https://doi.org/10.18231/j.joapr.2021.1.8

11.   Kumar, K., Adesh, Teotia, D., & Ikram. (2022). Development and Evaluation of Medicated Chewing Gum Formulations of Ondansetron. Journal of Drug Delivery and Therapeutics, 12(1), 133–135. https://doi.org/10.22270/jddt.v12i1.5207

12.   Lakshmi, S. V., Yadav, H. K. S., Mahesh, K. P., Uniyal, S., Ayaz, A., & Nagavarma, B. V. N. (2014). Formulation and evaluation of medicated chewing gum as antiplaque and antibacterial agent. Journal of Young Pharmacists, 6(4), 3–10. https://doi.org/10.5530/jyp.2014.4.2

13.   LALL DIPESH, SHRUTI, R., & PRANAY, S. (2020). FORMULATION AND EVALUATION OF NEW MEDICATED CHEWING FOR THE TREATMENT OF NAUSEA AND VOMITING INDUCED BY CHEMOTHERAPY, RADIATION THERAPY, AND POST-OPERATIVE CONDITIONS IN CANCER. Asian Journal of Pharmaceutical and Clinical Research, 157–160. https://doi.org/10.22159/ajpcr.2020.v13i4.37094

14.   Lieberman, H. A., Lachman, L., & Schwartz, J. B. (1989). Pharmaceutical dosage forms—Tablets. Dekker.

15.   Mansoori, R., Jain, D., & Bishnoi, R. S. (2022). FORMULATION AND EVALUATION OF MEDICATED CHEWING GUM OF EGCG (EPIGALLOCATECHIN GALLATE) ENRICHED EXTRACT OF CAMELLIA SINENSIS (GREEN TEA) FOR PERIODONTAL DISEASE. Journal of Advanced Scientific Research, 13(08), 79–86. https://doi.org/10.55218/JASR.202213812

16.   Maslii, Y., Ruban, О., & Kutsenko, S. (2020). SELECTION OF FLAVOUR ADDITIVES AND METHOD OF THEIR INTRODUCTION IN THE COMPOSITION OF COMPRESSED MEDICATED CHEWING GUMS. EUREKA: Health Sciences, 2, 59–66. https://doi.org/10.21303/2504-5679.2020.001189

17.   Nowosielska, M., Baginska, J., & Kierklo, A. (2021). Chewing gum with added chitosan http://www.jidmr.com Magdalena Nowosielska and et al Chewing Gum with Added Chitosan Reduces the Number of Cariogenic Bacteria Colonies in Human Saliva. In Journal of International Dental and Medical Research (Vol. 14, Issue 1, pp. 12–16). http://www.jidmr.com

18.   Paradkar, M., Gajra, B., & Patel, B. (2016). Formulation development and evaluation of medicated chewing gum of anti-emetic drug. Saudi Pharmaceutical Journal, 24(2), 153–164. https://doi.org/10.1016/j.jsps.2015.02.017

19.   Patel, V., Desai, T. R., Dedakiya, A. S., Bandhiya, H. M., & Patel, V. P. (2017). MEDICATED CHEWING GUM: A REVIEW. www.ijupls.com

20.   Poulsen, J., Nielsen, K. A., & Bauer-Brandl, A. (2022). Raman Imaging as a powerful tool to elucidate chemical processes in a matrix: Medicated chewing gums with nicotine. Journal of Pharmaceutical and Biomedical Analysis, 209. https://doi.org/10.1016/j.jpba.2021.114519

21.   S., M., A., S., A., J., A., K., S., M., & A., K. (2023). Formulation and Development of Medicated Chewing Gum Containing Ondansetron and Domperidone. International Journal of Newgen Research in Pharmacy & Healthcare, 80–86. https://doi.org/10.61554/ijnrph.v1i1.2023.19

22.   Sahu, J. K., Prasad, S., Prasad, M. S., & Pharm, M. (2023). Development and Characterization of Domperidone Containing Medicated Chewing Gum Formulations. Int J Med Phar Sci |, 13(9). https://doi.org/10.31782/IJMPS.2023.13902

23.   Shete, R. B., Muniswamy, V. J., Pandit, A. P., & Khandelwal, K. R. (2015). Formulation of Eco-friendly Medicated Chewing Gum to Prevent Motion Sickness. AAPS PharmSciTech, 16(5), 1041–1050. https://doi.org/10.1208/s12249-015-0296-y

24.   Solanki, P., & Chandra, A. (2018). Medicated Chewing Gum-A Novel Drug Delivery System: An Updated Review. www.ajadd.co.uk

25.   Soni, H., Mishra, A., & Prasad, J. (2022). MEDICATED CHEWING GUM: AN UPDATED REVIEW. In Certified Journal │ Harsha et al. European Journal of Pharmaceutical and Medical Research (Vol. 9). www.ejpmr.com

26.   Thivya, P., Durgadevi, M., & Sinija, V. R. N. (2021). Biodegradable medicated chewing gum: A modernized system for delivering bioactive compounds. Future Foods, 4. https://doi.org/10.1016/j.fufo.2021.100054

27.   Wen, Z., Shen, M., Wu, C., Ding, J., & Mei, B. (2017). Chewing gum for intestinal function recovery after caesarean section: A systematic review and meta-analysis. BMC Pregnancy and Childbirth, 17(1). https://doi.org/10.1186/s12884-017-1286-8

28.   Zieschang, L., Klein, M., Krämer, J., & Windbergs, M. (2018). In vitro performance testing of medicated chewing gums. Dissolution Technologies, 25(3). https://doi.org/10.14227/DT250318P64