Rahath F S et al / Int. J. of Pharmacy and Analytical Research Vol-8(1) 2019 [138-144]

ISSN:2320-2831

IJPAR |Vol.8 | Issue 1 | Jan – Mar - 2019 Journal Home page: www.ijpar.com

Research article Open Access

Medicated gums – An Overview S. Rahath Fathima*, V. Viswanath, M. Malleswari, M. Panitha, N. Govardhan Reddy, P. Ramakrishna Reddy, N. Sreedevi Department of Pharmaceutics, PRRM College of Pharmacy, Kadapa, Andhra Pradesh, India. *Corresponding Author: S. Rahath Fathima Email: [email protected]

ABSTRACT Now-a-days, there is increased interest on the formulation of oral delivery systems the reason behind this the ease of administration offered by oral route. Besides its ease, oral route offers a variety of advantages over others. Medicated chewing gum is one the technological advancement in the field of oral systems. In recent years, chewing gums gained increased acceptability among the patients because of its advantages like local and systemic effects, avoidance of first pass metabolism, fast action with fewer side-effects etc. Chewing gums provide feasibility of removing the chewed mass from the oral cavity at times needed without any invasive means. Medicated chewing gums uses a into which other additives like elastomers, , softeners, fillers, colors, flavors, sweeteners and ofcourse an active drug are incorporated. They provide a beautiful means of self-medication and can be administered anytime, anywhere without need of water. Drug release from the chewing gums is directly proportional to the extent we chew the gum mass in the oral cavity. Thus, in near future we may find various drugs formulated in the form of chewing gums. The current review presents a brief idea on the history, advantages, composition, manufacturing and evaluation of medicated chewing gums. Keywords: Chewing gum, Gum base, Plasticizers, Elastomers, Mucosa, Saliva.

INTRODUCTION cessation, travel illness and freshening of Chewing gum is a pleasure that almost all mouth. In recent years, they are considered as people use it the world wide. These are used as a friendly oral mucosal drug delivery system. [1] convenient modified release drug delivery system. When compared to other routes of administration, Chewing gums usually contain gum core, which is oral route is very convenient for patients due to either coated or not coated. Commercially available various advantages. medicated chewing gums are used for pain relief, Medicated chewing gums are solid single dose preparations that have to be chewed but not

www.ijpar.com ~138~ Rahath F S et al / Int. J. of Pharmacy and Analytical Research Vol-8(1) 2019 [138-144] swallowed. They contain one or more active The first chewing gum was marketed in 1948 in ingredients that are released by chewing. Basis for USA i.e. State of Maine pure gum. introducing medicated chewing gums in today‟s Aspergum is the first chewing gum launched in market is to provide the release of drug substances 1928 for analgesic activity. Dimenhydrinate is directly into bloodstream faster than pills. another commercially available chewing gum for Medicated chewing gums are intended to be .first patent was issue to DR.W.F chewed for a certain period of time , required to Semple who was a dentist of ohio in 1869.in 1999 deliver dose, after which remaining mass is December new England journal of medicine discarded .During chewing process drug contained ,reveals that chewing gums increases energy from in a gum is released into saliva, and could be 58k.cal hour to 70 k.cal per hour. [3,4] absorbed through oral mucosal or swallowed reaching for GI absorption. ADVANTAGES OF CHEWING GUM Chewing gums contain water soluble and water [5] insoluble portions .water soluble portions include Chewing gums provide the following plasticizers, elastomers, fillers and mineral advantages adjuvants. Water insoluble portion includes 1. Chewing gums have pleasant taste. sweeteners, antioxidants, softeners, bulking agents and emulsifiers. Chewing gums are now 2. High availability. extensively used as drug delivery agents for many 3. GI suffers less from effect of excipients. components in order to treat oral and throat 4. Fast onset of action. infections .Particularly, for children this is very convenient method of administration when 5. Fewer side effects. compared to tablets, . Nowadays, chewing 6. High acceptance of children. gums must meet the high quality standards as 7. Easy administration without water. tablets. In particular, anecdotal effect of chewing 8. Excellent for acute medication. gum on weight loss must also be studied [1,2]. 9. Reducing over dosing risk. HISTORY 10. To help reduce cravings. Homosapiens use different natural resources for 11. Treatment complete at any time. survival like shrub, herb, , and utilized 12. No first pass metabolism. them in the form of food, wood, medicine, shelter etc. Ancient people know how to use plant parts. 13. Both systemic and local delivery. For example, before invention of tooth brush they 14. Removal of gum at any time. used Azadiractha indica (neem) to clean their teeth 15. Provide relief from stress. and for its antibacterial action. In the same way, chewing gums today are used as they provide antimicrobial actions and prevent dental caries. In STRUCTURE AND FUNCTIONS OF the recent trend, researchers for drug loaded ORAL MUCOSA chewing gum and smoke session chewing gum. Oral mucosa is consisting of three different Chewing gum has been used since centuries by types of cells they are mayanIndians chewed form sapodilla tree to clear their mouth and fresher their teeth. These 1. Masticatory mucosa medicated chewing has been used since world war- II due to shortage of bases, due to 2. Lining mucosa enhanced development of systemic gum bases that 3. Specialized mucosa are used now a days. Chewing gums has old and Masticatory mucosa withstand abrasion and long history in 50 AD, Greek sweetened to breathe shearing forces of Masticatory process .lining and clean their teeth by Mastic resin from bark of mucosa cover no keratinized tissue .mucosa has mastic tree. capable of elastic deformation , stretches to speech .Epithelium of humans varies in thickness

www.ijpar.com ~139~ Rahath F S et al / Int. J. of Pharmacy and Analytical Research Vol-8(1) 2019 [138-144] according to region .regional difference in keratinized tissues .Turn over time is slow for morphology result in different permeability keratinized tissue .example: hard palate 24 days characters these influence on design of drug than non keratinized tissue and also there is delivery system .Aging and disease condition result accumulation of liquids fluids lipids cytokeratin‟s in loss of this balance .This cause thinking are less in keratinocytes and glycogen content is (atrophia) thickening ( hypertrophic)of Epithelium also more in keratinocytes. .human tissue contain keratinized and non

Fig. no.1 Distribution of masticatory, lining and specialized mucosa in buccal cavity

CHEWING GUM AND SALIVA intended for chewing .It contains one or more Chewing gum has powerful defense mechanism active ingredients that are released during chewing in body saliva. Saliva is important to oral health by providing local or systemic action after and it is protector of oral cavity, chewing gum is absorption through buccal mucosa and increases the saliva without drugs .Increasing saliva . in mouth is accomplished by stimulation of flavors Uses of medicated chewing gum „and GI actions of chewing .saliva has three protective mechanisms they are:  Chewing gums are used to improve  Ca+ and k+ ions produce remineralization of  oral health dental caries lesions ,saliva contain  process antibacterial agents  Memory functions  Dilutes and washes away food particles.  Help in managing body weight  Bicarbonate neutralizes and buffers plague  Help in reducing symptoms like nausea and acids [6, 7, 8]. vomiting. Definition of medicated chewing gum  Play a vital role in the treatment of gingivitis, Chewing gum is a solid dosing medicinal form throat and oral infections, acidic problems, with a base consisting mainly of gum, which is

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xerostamia, pharyngeal infections, travelilnes  Protein based sweeteners and motion sickness  Dipeptide based sweeteners.  Used in smoking cessation. Example are , , aspartate, Composition of chewing gum sucrose and sodium saccharin salts, calcium saccharin salts. Basic raw material for all chewing gum is natural gum which is obtained from sapodilla Coloring agents tree .chicle is very expensive so we use synthetic These are incorporated into gum base as 6% material like gum base. Chewing weight of gum base composition. Coloring agents gum has two parts: water soluble portions, water include pigments, titanium dioxide, food colours insoluble portions. and dyes suitable for food drug and cosmetic Gum base applications. Chewing gum is insoluble and inert non Flavouring agents [ 3] nutritive product used to soluble of chewing gum . These are essential oils, synthetic flavors, such Atypical gum base consisting of formula: as citrus oil, fruit essences, oil, winter sweeteners (30-60%), elastomers (10%), gum bases green oil, spearmint oil, anise oil. [9, 10] (20-90%), softeners (5-35%), fillers (4-50%), and flavoring agents (2-5%), preservatives (0.1%). MANUFACTURING METHODS Plasticizers Manufacturing of chewing gum can be prepared Plasticizers incorporated into gum base for by different methods they are classified in the variety of desirable consistency and texture following: properties, Plasticizers such as stearic acid,  Direct compression method potassium stearate acetylated mono glyceride,  Conventional / traditional method (melting) paraffin , oleic acid, vegetable oils.  Freezing, grinding & method Elastomers Direct Compression Method These are obtained as natural and synthetic rubbers. Gum base contain elastomers solvents to A new technology is developed for preparation softening gum base component .elastomers are of chewing gums is direct compression method. terpene such as of glycerol, methyl The direct compression method used for overcome esters of resins. Synthetic elastomers such as limiting of melting and freezing methods. SPI bufadiene, polyethylene mixtures, nontoxic vinyl pharma developed the Pharma gum it is a [2] polymers such as polyvinyl alcohol. Elastomers compactable gum system. Pharma gum is a used amount of 5-75% by weight of gum base. mixture of with a chewing gum base. It regarded as a safe (Gras). Pharmagum exists in Adjuvants three forms i.e. S, M & C forms. Pharmagum S has Talc, calcium carbonate others are used. less gum base when compared with pharmagum M. Mineral adjuvants are magnesium carbonate, Pharma gum “M” contain mannitol & gum base. calcium carbonate, aluminum hydroxide, aluminum Pharma gum‟s” contain sorbitol & gum base. silicate calcium phosphate used as fillers. Formulation prepared by pharmagum S & M is similar to appearance. Chewing gums Antioxidants prepared by using direct compression method is 10 These are used to prevent oxidation reaction times crumbled and harder, when applying of such as propyl gallate, butylated hydroxy toluene. pressure they release drug faster than conventional Sweeteners methods. When compared with traditional method formulation prepared by pharma gum S, M, and C  Sweeteners available it enables formulators to utilize gum delivery  Water soluble sweetening agents system quickly and more cost effectively.  Water soluble artificial agents

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In this method, :first prepare formulation before it by keeping in it refrigerator by freezer apparatus tableting by adding granulating agents, sweet, at temperature -15c, after it crushed it with cutter to emulsifiers, Antioxidants etc… form minute particles, then after it they minute In this first step is dry mixture of gum base, particles are heat to a temperature to make them granulating agent then add all active ingredients to adhere to each other and form uniform and formulation then directly compressing chewing consistent texture with low specific gravity. gum into tablets Coolants such as carbon dioxide (-15°c) and nitrogen hydro carbon is preferred in some Conventional/traditional method times chewing mixture composition, precipitated Preparation of chewing gum by using traditional silica and solid carbon dioxide is ground in a mill method has 2 types there are grinder. In first step, then addition carbon dioxide  Conventional fusion method and silica are add to ground composition and  Conventional fusion mixing technique further ground in second step for prevention of sticking to grinding apparatus we added phosphate First step is melt and soften the gum base at and alkaline earth metal phosphate. 60°c and place this mixture in kettle mixture it contain blades soften the base, then , sweet, Tableting Method glycerin, taste agents are added to gum base, after After coolant remove from , powder mix at 40°c flavor agents are added, followed by with binders, coating agents, lubricants sweet etc… cooling and rolling is done, after that rolled all this are compactable with chewing gum base in chewing gum is cut into pieces of desired shapes a small mill blender. Next use “ fluidized bed and sizes. reactor “ for formation of powder into granules and Second type of conventional method is if sugar coating of powder/ granules with coating agents, contain chewing gum is needed, corn is this prevent agglomeration process. added to mixer, then powdered sugar is gradually Then granules mixed with anti adherents like added, after that plasticizers and sweet added, due talc. Then in “ V “ type blender mixture is blended, to volatile nature of flavoring agents there are screened and compressed by punching machine by added at the end of preparation. Mixing is maintaining proper temperature [11,12]. continued until it forms homogenous mass, at least 8 minutes mixing is continued. After formation of matrix preparation, FACTORS AFFECTING RELEASE OF mixing it well, gum base add to chamber all at ACTIVE INGREDIENTS There are several factors affecting release of once. The particles are heated and mixed before active ingredients of medicated chewing gum are: adding all other ingredient1s to gum base, in this Environmental factors mixing continue 10 to 20 minutes, then gum is  Salivary glands cooled up to 48hrs. Finally gum cut into desired Drug is placed either adjacent to salivary shapes. glands or over a duct because results Difference between the conventional (fusion) method sweet and other ingredients added to excessive wash out of drug it cause molten gum base, but in conventional (fusion) difficult to achieve high local drug method mixing technique, sweet matrix is first concentration. formed, then gum base as pellets are added.  Saliva COOLING, GRINDING AND Saliva contains pH 6.5-7.5 and 99% of TABLETING METHOD water. Salivary flow rate increase cause Cooling and grinding secretion of watery saliva, salivary pH is In this added the gum base with flavors, sweet important for passive diffusion of corn , flavoring agents colorant and then cool unionized drug.

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Chewing rate and chewing time recommends 20ml of buffer in chewing chamber of 40 ml and chewing rate is 60 strokes per minute. Chewing rate also effect the drug release, By using European pharmacopeia several studies average chewing rate is 60 chews / min. Chewing have been carry out, results indicate and time also effects rate of drug release chewing time reproducible. is 20-30min. Unofficial chewing single module apparatus Contact Time To study dissolution charecters of mcg Local and systemic effect depending on unofficial apparatus are used and these are chewing gum contact time in oral cavity .chewing designed by wennergren. This apparatus contain time 30 min consider as close to ordinary use in temperature control reserviour for dissolution clinical trials. medium and two pistons. Upper jaw has flat surface Formulation factors and it is paraller to central part of lower surface. It Amount of gum base and composition also contain small bowl with flat bottoms. This bowl is affects the rate of release of drug .fraction of gum used to prevent sliding of chewing gum during increases release rate decrease. mastication. During one cycle of chewing, one piston on each side shift towards to each other. Membrane factors When these two pistons get together chewing gum Permeability and thickness difference affect rate presses between them. For carrying of drug release and extent of drug release. Absorption membrane test quantity of chewing gum place in the 20ml of thickness, lymph drianage, enzyme content also dissolution medium and maintain the temperature affect rate of drug release. 37°c , twisting and pressing forces are transmitted to gum by the pistons at chew rate 60strokes per Inter Individual variability minute. At 3,5,10 minutes intravels samples are Drug release from medicated chewing gum is collected and analyse for percentage drug release. vary from person to person .Invitro study done by European pharmacopoeia suggest 60 cycles per INVIVO CHEW-OUT STUDIES [13] minute chewing rate for release of drug property . Release of drug in saliva

Minimum of four human volunteers are selected EVALUATION PARAMETERS (to female and two male). Volunteers are instructed Product performance Test to clean their teeth by water and allowed chewing There are two tests are performed to check drug gum for 15mins, so that its maximum release has characters they are product quality performance taken, after 2,4,6,,8,10,12,14,15,mits samples of tests .USP containing individual monographs with saliva are taken. Sample can be diluted with solvent product quality test for nicotine polacrilex and and absorbance is analyzed by analytical method. nicotine polacrilex gum .pH.eur .adopted Urinary excretion profile of medicated monographs on chewing gum and those chewing gum monographs describe apparatus for dissertation testing of chewing gum . In this also minimum of four human volunteers are selected for formulations studies. This method Invitro drug release Test useful only to those drugs which are excrete Official MCG Chewing gum apparatus through urine. Instructed volunteers that they are don‟t take any medicine last 48 hrs. They are fasted These apparatus consist of pair of horizontal overnight and emptied their bladder. Samples are pistons and chewing chamber supply with vertical collected after administration of chewing gum at piston working alternative to horizontal pistons that intervals of 1,2,3,4,6,8,10,11,12,24 hrs.Volunteers ensure gum always positioned in correct place are asked to drink water at every 30 minutes and during mastication process and the temperature of urine samples are analysed. chamber maintained at 37° – 0.5° c ,also adjust volume of medium , twisting movement , distance between jaws. European pharmacopoeia

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Buccal absorption Test acids and enzymes, low first pass metabolism, however there new and old appalactiom, prove our Healthy human volunteers are selected and statement as it can be seeing that they are treatment fixed volume of drug of known for pain, smoking, motions skiness decay. concentration at different pH values of 7.5, 7.8,8 in Scientists and researchers should also oral cavities for 15 minutes and then expelled considered new formulation for chewing gum for out.Sample is analysed for drug content and back increase variations of chewing gum due to patient‟s calculated for buccal absorption [14, 15]. different styles and providing release pattern for

chewing gum containing drugs. CONCLUSION It can be concluded that the chewing gum used Acknowlwdgement as carrier for many drugs, where extended local We acknowledge P.Ramireddy memorial action and release desired. They can be used as college of Pharmacy for their kind help during the taste masking of certain drugs and produced work tenure systemic and buccal effects in oral cavity. Chewing gum not only offer clinical benefits also used as efficient drug delivery system and protect against

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