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Home , Mouthwash, Toothpaste, Tooth brushing

FORMULATION INGREDIENTS FOR AND

Edina Vranic1*, Amela Lacevic2, Aida Mehmedagic3,4, Alija Uzunovic4

1 Department of Pharmaceutical Technology, Faculty of , University of Sarajevo, Cekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina 2 Department of Dental Pathology and Endodontics, Faculty of Stomatology, University of Sarajevo, Bolnicka 4a, 71000 Sarajevo, Bosnia and Herzegovina 3 Department of Pharmacokinetics, Faculty of Pharmacy, University of Sarajevo, Cekalusa 90, 71000 Sarajevo, Bosnia and Herzegovina 4 Institute for Quality Control of Medicines, M. Tita 9, 71000 Sarajevo, Bosnia and Herzegovina

* Corresponding author

Abstract Ingredients of toothpastes and mouthwashes In order to achieve the multi-claim products required for the dental care category, it is necessary for the formulator A in defined as a semi- material for re- to use a variety of different ingredients. This places a moving naturally occurring deposits from teeth and is number of demands on the development process. Innova- supposed to be used simultaneous with a . tions in the areas of pharmaceutical technology have con- A is defined as a non-sterile aqueous tributed to the formulation of the products having superi- used mostly for its deodorant, refreshing or ef- or as well as other attributes that may contribute fect. Mouthwashes or rinses are designed to reduce oral to clinical response and patient acceptability. Improved bacteria, remove food particles, temporary reduce bad clinical efficacy and tolerability, along with conditioning breath and provide a pleasant taste. signals, should encourage patient compliance with oral Mouthwashes (mouthrinses) are generally classified as ei- further complementing professional efforts di- ther cosmetic or therapeutic or a combination of the two. rected at disease prevention. The most effective way of Cosmetic rinses are commercial products that remove oral preventing the development of dental disease is in con- debris before or after brushing, temporary suppress bad trolling the production of . It is formed by breath, diminish bacteria in the mouth and refresh the microbial action. The removal of plaque from the teeth mouth with a pleasant taste. Therapeutic rinses often have and related areas is essential for the maintenance of a the benefits of their cosmetic counterparts, but also contain healthy mouth. an added active ingredient, (for example or chlo- In this paper we have presented the main components of rhexidine), that help protect against some oral diseases. toothpastes and mouthwashes. For the active ingredients, The amount of the different ingredients in mouthwashes their supposed effect as therapeutic agents is also ex- varies from product to product. Some practically have the plained. same composition as toothpastes, although they do not Key words: formulation, ingredients, toothpastes, mouth- contain abrasives. Distinct from toothpastes most mouth- washes washes contain alcohol, as a preservative and a semi-ac- tive ingredient. The amount of alcohol is usually ranging Introduction from 18 - 26 % .

The most effective way of preventing the development of Abrasives dental disease is in controlling the production of dental plaque. Plaque is a soft thin layer which deposits on teeth, Abrasives are the substances that are used for abrading, and all appliances fitted in the mouth. It is formed grinding or polishing. They remove substances adhering by microbial action. Dietary sugars, in particular , to the surface of the teeth without scratching it and bring contribute to the formation of plaque and their presence out their natural luster. increases the rate of formation and thickness of plaque. One of the mayor properties of the abrasive is hardness. The removal of plaque from the teeth and related areas is The degree of abrasivity depends on the hardness of the essential for the maintenance of a healthy mouth (1). abrasive, the morphology of the particles, and on the con- In this paper we have presented the main components of centration of abrasive in the . As the hardness of the toothpastes and mouthwashes. For the active ingredients, enamel on the surface is 6-7 on the Moh's scale, the their supposed effect as therapeutic agents is also ex- hardness of an abrasive should be 3 or less. For practical plained. purposes, the particle size should be 20µm or less; if it is

BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 51 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org more than this they may damage the tooth surface and Binders gums. The abrasives found in toothpastes are often not as hard as the enamel, but as hard or harder than the dentine. Binders are used to prevent the separation of and Abrasives are most often found as crystals, small and ingredients and give an appropriate degree of vis- smooth particles are preferred to avoid . Nee- coelasticity and form to the toothpaste. They can prevent dle and rod-shaped particles must be avoided (2). the toothpaste from drying out by binding water. Also, Although many methods have been suggested for meas- they have an influence on the dispersion, foaming, rinsing uring the abrasive effect incorporated in tooth- and other qualities of the toothpaste in the oral cavity. The pastes, the RDA method (Radioactive Dentine ) most widely used binder at present is sodium carboxym- is the most widely accepted in the world today. In this ethylcellulose (CMC). method, an extracted is irradiated to convert the 31P in its dentine to 32P. The tooth is then put into an Carboxymethylcellulose is physiologically inactive, it dis- abrasion testing machine together with an abrasive and solves in water, it is very compatible with other ingredi- the abrasion of 32P is measured using a radioactivity coun- ents, highly stable and relatively low in price. There are ter. The pH of abrasives should range from weakly acidic many types of CMC having a variety of different charac- to weakly alkaline and they should be white powders teristics stemming from different degrees of hydroxy which are insoluble in water, flavourless and odourless. group substitution and polymerisation, so it is necessary The following substances are widely used abrasives, to select the most appropriate one for the purpose in mind. which satisfy these conditions: Other known cellulose derivatives include methylcellu- lose, hydroxyethylcellulose and hydroxypropylcellulose.

Calcium carbonate (CaCO3) Examples of other binders used are polysaccharides such A fine, white, odourless, microcrystalline powder, practi- as sodium alginate, carrageenan and xanthan gum; syn- cally insoluble in water (3). This abrasive has been used thetic like sodium polyacrylate and inorganic for a very long time. Its abrasiveness is generally higher clay minerals as bentonite and laponite. than that of phosphate. There are two types-a heavy and precipitated type. The raw material for the for- Sodium alginate mer is and for the latter calcium hydroxide. It is obtained from algae belonging to the Phaeophyceae, mainly species of Laminaria (4). It consists chiefly of the sodium of alginic acid. A white or pale yellowish- Calcium phosphate, dibasic; Calcium phosphate, di- white powder which is odourless or almost odourless and basic, dihydrate (CaHPO4, CaHPO4 x 2H2O) tasteless. Slowly soluble in water, forming a viscous, col- There is a dihydrate form and an anhydride form. As the loidal solution; practically insoluble in alcohol and in anhydride form is harder than the dihydrate form, it is not ether. often used by itself. The dihydrate form has a mild abra- Sodium alginate has little surface activity and its emulsi- sive effect and feels good on use. It is neutral in pH and fying power is achieved by increasing the of the has good compatibility with other ingredients. However, aqueous phase. It is used as a suspending and thickening when it is in toothpaste for a long period of time, it loses agent and in the preparation of water-miscible pastes, its water of crystallisation, changes to the anhydride form creams and . According to the viscosity required, from and makes the toothpaste go hard. For this reason a mag- 1 to 10 % is used in the preparation of pastes and creams. nesium salt or other stabiliser is added (2). Carrageenan Silica, silica hydrate (SiO2, SiO2 x nH2O) A dried aqueous extract from species of Chondrus, Gigar- The main ingredient of the silica used in abrasives is high tina, Eucheuma or other members of the families Gigarti- purity amorphous and there are varieties naceae, Solieriaceae, Hypneaceae and Furcellariaceae. A of different types whose properties vary with the method white to yellowish coarse or fine, almost odourless pow- of production. Silica is very suitable for use in toothpast- der with a mucilaginous taste. Soluble 1 in 100 of water es containing fluoride because no insoluble salt is formed at 85°C. It disperses more readily if first mixed with alco- when it reacts with fluoride. As its refractive index is low- hol. It is used as an emulsifying, suspending and thicken- er than that of other abrasives, silica can be used to make ing agent in formulations of toothpastes, creams and clear tootpastes. . Carrageenans are galactans or polymers of D- galactose, are heavily sulfated, and are anions with multi- Other abrasives ple electrolytes of molecular weight ranging from 105 is also used as an alternative to cal- to106. All carrageenans have a linear structure of (AB)n cium phosphate, dibasic, because it is cheaper. Other abra- type, with alternating 1,3 and 1,4 bonds. Classically, sev- sives such as calcium pyrophosphate, insoluble sodium en types of carrageenans are distinguished as a function metaphosphate, magnesium carbonate and alumna may of the nature of the sequence. These are ι, κ, λ, µ, ν, θ, also be used for special types. ξ carrageenans (5).

52 BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org

Carbomers Foaming agents These are synthetic high molecular weight polymers of acrylic acid cross-linked with polyalkenyl ethers of sug- The functions of foaming agents are to disperse the tooth- ars or polyalcohols. They are produced in several grades paste throughout the oral cavity in order to enhance the characterised by the viscosity of a defined solution. cleaning effect and, acting as a , clean away the White, hygroscopic powders with a slight characteristic dirt inside it. Also, by means of their volume of foam, odour. They swell in water and in other polar solvents aft- they give a feeling of thickness, and satisfaction. Surfac- er dispersion and neutralisation with sodium hydroxide tants having excellent foaming, dispersion, , solution (6). It also soluble in water, alcohol and . permeation, cleansing and hard water resistance qualities Carbomer is used in toothpastes as a binder (thickener). as well as no toxicity or irritation, are selected for foam- ing agents. Xanthan gum Xanthomonas campestris is a bacterium which commonly lower the surface tension of the liquid envi- develops on certain species of Brassicaceae where, by us- ronment in the oral cavity so that the substances in the ing the vegetable substrate, it produces a gummy exudate: toothpaste/mouthwash can contact the teeth more easily. xanthan "gum", a high-molecular-mass anionic polysac- They penetrate and dissolve plaque. This makes it easier charide. It exists as the sodium, potassium or calcium salt to clean the teeth. The foaming effect produced by the (6). surfactants is also beneficial in cleaning the teeth, and Industrially, this "gum" is produced by a bacterial culture contributes to remove debris and gives a feeling of clean- on correctly buffered and aerated media containing carbo- ness. Another function of the surfactant is in dispersing hydrates with Xanthomonas campestris. Upon completion the flavours in the toothpaste/mouthwash. Because, they of fermentation, the is recovered by precipitation go into the mouth, attention is also paid to taste and smell. with isopropanol, filtered, dried, and crushed (7). The one most frequently used at present is sodium lauryl sulfate; other examples are sodium lauryl sarcosinate, so- It is a -coloured powder. Soluble in hot and cold dium alkylsulfo succinate, sodium cocomonoglyceride water, xanthan gum forms aqueous of which the sulfonate and sucrose fatty acid esters. viscosity remains practically unchanged by temperature changes, as well as pH changes. Sodium lauryl sulphate (SLS) A mixture of sodium alkyl sulphates, consisting mainly of The behaviour of these solutions is of the pseudoplastic- sodium dodecyl sulphate. It is a white or pale yellow pow- type: decrease in viscosity proportional to shearing and der or crystals with a slight characteristic odour. Freely instant recovery of the initial viscosity upon discontinua- soluble in water; partly soluble in alcohol (6). It exhibits tion of shearing. Incompatibilities are rare (borates, hypo- high affinity for proteins and is a strong denaturing agent. chlorites, peroxydes, free radical generators). The gum is Incompatible with cationic materials and with acids below compatible with most , with moderate surfactant con- pH 2.5. Sodium lauryl sulphate may be irritant to the skin centrations, and with most preservatives; it tolerates alco- and mucosa. It may also damage the mucosal mucin layer hol concentrations up to 50% percents. Compatible with by denaturing its glycoproteins (8). The epithelium will most vegetable hydrocolloids, it does not form gels by it- then be more exposed for irritants and this can result in self, but it forms thermally reversible gels. It is devoid of aphtous ulcerations in some patients. It has also been toxicity. Xanthan gum is used as a stabiliser, binder claimed that there is a connection between the use of (thickener), and emulsifier. toothpaste or mouthwash containing SLS and an in- creased frequency of recurrent aphthous ulcers (RAU) in some patients. A product without SLS may thus be recom- mended for patients with RAU (8). The adverse effects of They prevent loss of water, and subsequent hardening of SLS have resulted in the development of toothpaste and the paste in the tube or when it is exposed to air. They also mouthwashes with alternative surfactants such as sodium provide creamy texture. These are short-chained polyalco- lauryl sarcosinate, socamidopopybetaine. Common for hols such as glycerol, (highly concentrated aque- these surfactants are that they are less irritating to the oral ous solution), and . mucosa. It is effective in both acid and alkaline solution and in hard water. Also, it has antimicrobial activity due to Solvents its ability to interfere with membranes and a variety of bi- ologic processes in microorganisms. Water is the most common solvent used in toothpaste. It dissolves the ingredients and allows them to be mixed. Al- Flavouring agents cohol is used in mouth rinses (mouthwashes) as a solvent and taste enhancer. They get rid of the unpleasant smell and taste of the other raw materials and give a cold, refreshing taste. Combina-

BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 53 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org tions of water-insoluble essential oils, such as , so contain fluoride, but in a non-therapeutic dose. Howe- , and are often used as fla- ver, there are fluoride-rinses with higher fluoride concen- vouring agents in toothpastes and mouthwashes. The fla- trations. vouring agents are solubilised and dispersed through the paste or liquid via the surfactant. The mechanism by which fluoride prevents caries is not clearly understood. It is known that the fluoride ion (F-) Sweeteners can replace the hydroxyl ion (OH-) in , the major crystalline structure of enamel. The substituted Sweeteners also improve the taste of toothpastes and crystal, called , is more resistant to acids, such mouthwashes and give them a mild and sweet taste. The as those produced by plaque bacteria, than the original hy- most common used sweeteners are sodium , sor- droxyapatite (9). bitol and glycerol. is a sweetener that is also As the tooth develops and enamel is formed, ingested flu- claimed to provide anti-caries activity. oride is incorporated into the enamel. Therefore, because enamel develops its outer layer first, more fluoride can be Colouring agents expected to be deposited on the outer layers as compared to the inner layers. It is this surface enamel layer contain- Most toothpastes and mouthwashes contain colour-sub- ing fluoride that imports caries resistance to a tooth. The stances which give them an attractive appearance. The incorporation of fluoride into enamel can be represented colour-substances are classified by the Colour Index (CI), as a chemical reaction: published by the Society of Dyers and Colourists and the American Association of Textile Chemists and Colourists, or by a system called the FD&C Colours. Titanium diox- ide is often added to toothpastes to give them a white col- our. It is also suggested that fluoride has anti-bacterial actions. Preservatives In an acidic environment, if fluoride is present, hydrogen fluoride (HF) is formed. HF is an undissociated, week ac- Preservatives prevent the growth of micro-organisms in id that can penetrate the bacterial cell membrane. The en- toothpastes and mouthwashes. Mostly, they include sodi- try of HF into the alkaline cytoplasmic compartments re- um benzoate, methylparaben and ethylparaben. sults in dissociation of HF to H+ and F-. This has two sep- arate, major effects on the physiology of the cell. The first Pharmaceutical agents is that the released F- interacts with cellular constituents, including various F-sensitive . The second effect One or more therapeutic agents are usually added to is an acidification of the cytoplasmic compartment caused toothpastes and mouthwashes. Most toothpastes today by the released protons. Normally protons are pumped out contain to prevent caries. Recently there has of the cell, but fluoride inhibits these processes. The de- been a development of different toothpastes with addition- creased intracellular pH will make the environment less al purposes, such as stain and removal, and pre- favourable for many of the essential enzymes required for vention of , sensitive teeth and gum problems. In cell growth (10). the following text the different pharmaceutical therapeu- As the most important anti-caries effect is claimed to be tic agents are categorised according to their claimed ef- due to the formation of calcium fluoride (CaF2) in plaque fect. and on the enamel surface during and after rinsing or brushing with fluoride. CaF2 serves as a fluoride reservoir. Anticaries agents When the pH drops, fluoride and calcium are released in- to the plaque fluid. Fluoride diffuses with the acid from Fluoride plaque into the enamel pores and forms fluoroapatite Fluoride is considered to be the most effective caries-in- (FAP). FAP incorporated in the enamel surface is more re- hibiting agent, and almost all toothpastes today contain sistant to a subsequent acid attack since the critical pH of fluoride in one form or the other. The most common form FAP (pH=4.5) is lower than that of hydroxyapatite (HA) is (NaF), but mono-fluoro-phosphate (pH=5.5). Fluoride decreases the demineralisation and in- (MFP) and stannous fluoride (SnF) are also used. The flu- creases the remineralisation of the enamel between pH oride amount in toothpaste is usually between 0.10-0.15 4.5-5.5, and hence the demineralisation period is shorten- %. Fluoride is most beneficial when the mouth is not ed (10). rinsed with water after . In this way a big- ger amount of fluoride is retained in the oral cavity. Xylitol Toothpastes are the main vehicle for fluoride. The com- A polyhydric alcohol (polyol) related to the pentose sugar, bined therapeutic and cosmetic mouthwashes usually al- xylose. White crystals or crystalline powder. Very solu-

54 BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org ble in water; sparingly soluble in alcohol (6). It has a levels of antiplaque activity. sweet taste and produces a cooling sensation in the mouth. Evidence has accumulated to suggest that itself Xylitol cannot be fermentated by oral microorganisms. It does not produce optimal plaque inhibitory effects with- is considered to be a cariostatic agent since it can inhibit out the addition of other chemicals which increase its an- the carbohydrate metabolism in different oral micro-or- tibacterial effect. Most commonly used are copolymer ganisms. Xylitol seems to be unique among the sugar al- PVM/MA [Poly(Methylvinylether/Maleic anhydride)] cohols in its inhibitory effect on glycolysis. The inhibito- and citrate. They enhance surface retention of triclos- ry effect on glycolysis has been related to the uptake of an (15). An antiseptic has to be retained in the oral cavity xylitol via a constitutive fructose specific PTS (phospho- for a certain amount of time in order to have antiplaque transferase) system and subsequent intracellular accumu- activity. The retention sites for triclosan are not yet estab- lation of xylitol-5-phosphate. Such a mechanism to lished, but the teeth and the micelles in saliva are suggest- reduced acid formation from glucose, and a reduction in ed. Triclosan also has antiinflammatory effect by acting the content in both plaque and sali- on the eicosanoid-cascade. Triclosan inhibits both cy- va (11). clooxygenase (COX) and lipoxygenase (LOX), and there- by inhibits the production of prostaglandins and leukotri- Calcium / Phosphate enes. Clinical studies also indicate that triclosan reduces Calcium and phosphate supplementation in a toothpaste oral mucosal irritation caused by sodium lauryl sulphate or mouth rinse will increase the concentration of these (16,17). ions in the oral cavity. In this way they improve reminer- alisation and increase fluoride uptake (12). Metal-ions The most widely used metal-ions in dental preparations are zinc (Zn2+) and stannous (Sn2+). These metals have the Several studies have shown that bicarbonate is one of the ability to limit bacterial growth, inhibit plaque formation, salivary components that potentially modifies the forma- inhibit the glycolytic sequence in oral anaerobic bacteria, tion of caries. It increases the pH in saliva, and in this way and to restrict the ability of plaque bacteria to convert urea creates a hostile environment for the growth of aciduric to ammonia (14). They can also inhibit some bacterial en- bacteria. Sodium bicarbonate can also change the viru- zymes. It is also possible that they can reduce the bacte- lence of the bacteria that cause . ria's ability to colonise the tooth surfaces. Animal studies have shown that toothpastes containing sodium bicarbonate reduce the amount of both Strepto- a) Stannous-ions coccus sobrinus and Streptococcus mutans, and this may Stannous-ions are added to toothpastes and mouthwashes reduce caries. Studies on human show a statistically re- in the form of stannous fluoride or stannous pyrophos- duction in number of mutans streptococci. Sodium bicar- phate. Stannous fluoride was frequently used as a vehicle bonate can also prevent caries by reducing enamel solu- for fluoride in dental preparations. At present time it is bility and increase remineralisation of enamel (13). rarely used, although extensive research during the last two decades has established that stannous fluoride pos- Anti-plaque agents sesses several interesting properties. It has been claimed that stannous fluoride is more effect- Sodium lauryl sulphate ive in caries inhibition than sodium fluoride and mono- It has been shown that the enzymes glucosyltransferase and flourophoshate. This is probably because stannous fluor- fructosyltransferase are incorporated in an active form into ide has additional properties compared with other fluor- the pellicle; and by synthesising glucan in situ from su- ide vehicles. However such differences are not always crose, can provide a surface for colonisation by Streptococ- statically significant in small-scale studies (18). Mouth cus mutans. These enzymes can be inhibited by SLS. Such rinses containing stannous fluoride have been found to re- inhibition can clearly retard the regrowth of plaque (14). duce the relative amounts of Streptococcus mutans and Streptococcus sanguis in plaque, to reduce the population Triclosan of Streptococcus mutans in saliva and to increase the sal- Triclosan is a non-ionic chlorinated phenolic agent with ivary levels of Lactobacilli (14). antiseptic qualities. Triclosan has a broad-spectrum effi- The stannous fluoride treated enamel becomes hydropho- cacy on Gram-positive and most Gram-negative bacteria. bic, a property which may contribute to the antiplaque ef- It is also effective against mycobacterium and strictly an- fect of stannous fluoride, since hydrophobic surfaces are aerobic bacteria, and against the spores and fungi of the less easily colonised by bacteria (18). The cariostatic pro- Candida species. The mechanism of its antiseptic action tection provided by stannous fluoride is dependent on a is by acting on the microbial cytoplasmic membrane, in- deposition of CaF reservoir on the tooth surface. Both the ducing leakage of cellular constituents and thereby caus- antiplaque effect and the inhibition of acid formation by ing of the micro-organisms. In spite of its activity in stannous fluoride are most likely caused by the oxidation vitro, clinical plaque studies have revealed only moderate of thiol groups which stannous fluoride is known to per-

BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 55 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org form. Stannous ions may inhibit bacterial glycolysis be- Anti-calculus agents cause the enzymes depend on the thiol group for their bi- ological activity (18). The antiplaque effect of SnF can These agents act by delaying dental plaque calcification, clearly also contribute to the cariostatic activity. thereby promoting plaque removal with normal tooth brushing (21). Of the anti-calculus agents, the crystal b) Zinc-ions growth inhibitors have been most extensively tested clin- Zinc is added to toothpastes and mouthwashes as zinc ically. chloride or zinc citrate. Zinc is a relatively non-toxic, non- cumulative essential trace element Zinc inhibits the PTS Pyrophosphate pathway of glucose uptake by Streptococcus mutans, Pyrophosphate has introduced in toothpastes to inhibit the Streptococcus sanguis and Actinomyses naeslundii, and formation of supragingival dental calculus (21). Pyro- the metabolism of glucose to lactic acid. The effects of phosphate is added as tetrasodium pyrophosphate, tetra- zinc are believed to be intracellular, resulting from the in- potassium pyrophosphate or disodium pyrophosphate. It hibition of sulphydryl enzymes, specifically I in has been shown that pyrophosphate has high affinity to the phosphotransferase transport system and aldolase and hydroxyapatite (HA) surfaces, probably by an interaction glyceraldehyde dehydrogenase in the glycolytic pathway. with Ca2+ in the hydration layer. By interacting with HA Zinc also inhibits the trypsin-like protease activity of Por- and the enamel surface, pyrophosphate reduces their pro- phyromonas gingivalis and of gingival- tein-binding capacity. It also has the ability to inhibit cal- is (14). The role of zinc in plaque inhibition or as a calcu- cium phosphate formation. It is therefore conceivable that lus inhibitory agent when used in toothpastes has been es- pyrophosphate introduced in the oral cavity through tablished by a number of workers (14). It is shown that toothpastes may affect pellicle formation. However, the P- surfactants enhance the plaque-inhibitory role of zinc O-P bond of pyrophosphate is known to be susceptible to (19). enzymatic hydrolysis by plaque and salivary phosphata- ses, and the effect may thus be of limited duration in the Essential oils oral cavity (14). Consequently, the tartar control tooth- Essentials oils of , menthol, and meth- pastes that contain pyrophosphate as a calculus inhibitor yl salicylate are thought to have anti-bacterial activity by also incorporate phosphates inhibitors that prolong the ac- altering the bacterial cell wall. Mouth rinses containing tivity of pyrophosphate in the mouth. these active ingredients have been reported to reduce plaque and gingivitis significantly. Studies have indicated that fluoride in combination with PVM/MA Copolymer gives a significant protection of py- rophosphate against phosphatases (22). The clinical con- Chlorhexidine formulations are considered to be the "gold sequences of a poorly formed or partly missing pellicle standard" antiplaque mouthwashes due to their prolonged are not known. Suggested consequences are abrasion of broad spectrum antimicrobial activity and plaque inhibi- teeth, increased demineralisation, and hypersensitivity of tory potential (20). The mechanism of action of chlorhex- teeth (14). idine is related to a reduction in pellicle formation, altera- tion of bacterial absorption and/or attachment to teeth, and Zinc-ions an alternation of the bacterial cell wall so that lysis occurs (9). Chlorhexidine is effective against both Gram-positive Zinc has anti-calculus effect due to its anti-plaque proper- and Gram-negative bacteria, but has most effect against ties, but in addition it is thought to influence calculus for- Gram-positive bacteria. mation by inhibiting crystal growth. Chlorhexidine is bacteriostatic at very low concentrations, especially against Streptococcus mutans. It also has effect Anti-dentine hypersensitivity agents against fungi, but non or little effect against spores. It al- so has effect against some viruses. Although the condition is referred to as "dentine hyper- Chlorhexidine is retained in the oral cavity for 24 hours sensitivity" it isn't really the dentine that is sensitive. The by binding to phosphate, sulphate and carboxyl groups in sensitivity of dentine is caused by fluid-filled tubules in bacteria, plaque, saliva and on the enamel surface. The an- communication with the pulp (14). ti-bacterial action is due to a disturbance of the transport through the cell membrane and of the bacterial metabo- Potassium salts lism, and by causing leakage through the cell membrane. Potassium ions are thought to act by blocking action po- Its antiviral effect is caused by interaction with the viral tential generation in intradental nerves (23). It is claimed protein cap. Local side effects of chlorhexidine including that potassium salts in dental preparations increase the disturbance of taste and staining of teeth, tongue and re- concentration of potassium ions around the pulpal nerves, storative materials have tended to restrict its use to only a and thereby depolarises the nerve. This can inhibit a nerve short term (20). response from different stimuli.

56 BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org

Anti-aphtous agents

Aminoglucosidase and glucose oxidase Sodium bicarbonate Enzymatic toothpastes and mouthwashes do not contain It is known that toothpastes containing high concentra- surfactants like SLS because the surfactant can denaturate tions of sodium bicarbonate are more effective in remov- the enzymes. SLS may induce adverse effects in oral soft ing intrinsic tooth stain than those not containing sodium tissues and increases the frequency of ulcers in patients bicarbonate (25). suffering from recurrent aphthous ulcers (RAU). The ul- cers were generally reported to be smaller and less pain- Anti-halistosis agents ful, to have a shorter healing time and the frequencies of aphthous ulcers episodes were decreased (24). Zinc-ions or halitosis originates mainly from the oral Whitening agents cavity. The unpleasant smell is due to the retention of an- aerobic, Gram-negative bacteria. These bacteria use sul- Whitening toothpastes do not lighten the colour of the phurcontaining amino acids as substrates in their produc- tooth structure; they simply remove surface stains with tion of volatile sulphur-containing compounds (VSC). abrasives or special chemical or polishing agents, or pre- VSC have a distinctly unpleasant odour even in low con- vent stain formation. centrations. Zinc inhibits the production of VSC in the oral cavity by interacting with sulphur in the amino acids Abrasives or their metabolism. Zinc can be retained in the oral cav- An abrasive is required for the effective removal of a dis- ity for approximately 2-3 hours after tooth brushing by coloured pellicle. Abrasives provide a significant whiten- binding to acidic substances on the , in the sa- ing benefit, particularly on smooth surfaces, but are of liva or on bacterial surfaces. limited use for areas along the gum line and interproxi- mally. Some whitening toothpastes contain coarse abra- Conclusion sives that can damage the dental tissue. In order to achieve the multi-claim products required for Dimethicones the dental care category, it is necessary for the formulator Dimethicones are versatile substances that ranges from to use a variety of different ingredients. This places a low molecular weight polydimethylsioxane fluids to high number of demands on the development process. Innova- molecular weight polymers that are gum-like in nature. tions in the areas of pharmaceutical technology have con- They cause a smooth surface on the tooth that prevents tributed to the formulation of the products having superi- stain formation. or efficacy as well as other attributes that may contribute to clinical response and patient acceptability. Improved Papain clinical efficacy and tolerability, along with conditioning Papain is a sulfhydryl protease consisting of a single pol- signals, should encourage patient compliance with oral ypeptide chain, extracted from the Carica papaya plant hygiene further complementing professional efforts di- (4). It is able to hydrolyse peptid bonds, and can also cata- rected at disease prevention. lyse the transfer of an acyl group. It is used in toothpastes as an non-abrasive whitening agent.

BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2004; 4 (4): 51-58 57 Edina Vranic et al.: FORMULATION INGREDIENTS FOR TOOTHPASTES AND MOUTHWASHES www.bjbms.org

References

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