Southeast University

Department of Pharmacy

Submitted to:

Md. ShahidSarwarLecturerHospital & Community PharmacyDepartment of PharmacySoutheast university

Submitted by:

Md. WaliullahWaliId. 2010000300031Batch- 15th(B)Department of PharmacySoutheast University

Date: 30 October 2013

Assignment on: Dental Pharmacy (Drugs used in dental cares and complications, Dental prophylactic

preparations)

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Table of ContentsTooth..........................................................................................................................................................................3

Human Teeth Anatomy...............................................................................................................................................4

Typesof Teeth............................................................................................................................................................5

Functions of teeth.......................................................................................................................................................6

Common Dental Problems..........................................................................................................................................6

Medications Used in Dentistry....................................................................................................................................8

Medication in dentistry...............................................................................................................................................8

I. Anesthetics...........................................................................................................................................................9

II. Analgesics/pain killers.......................................................................................................................................10

A. Paracetamol/ Acetaminophen.................................................................................................................10

B. Non-steroidal anti-inflammatory drug (NSAIDs)[8]....................................................................................11

C. Corticosteroids ointment.........................................................................................................................11

III. Mouth washes..................................................................................................................................................11

IV. Antibiotics........................................................................................................................................................12

V. Antifungal.........................................................................................................................................................13

VI. Antiseptics.......................................................................................................................................................14

VII. Dry Mouth Drugs............................................................................................................................................14

VIII. Muscle Relaxants...........................................................................................................................................14

IX. Drugs to Control Plaque and Gingivitis.............................................................................................................14

X. Other dental medications.................................................................................................................................14

Fluorides...........................................................................................................................................................14

Benzodiazepines...............................................................................................................................................15

Saliva substitutes..............................................................................................................................................15

Dental Prophylactic Preparations..............................................................................................................................15

Mouthwash...............................................................................................................................................................15

Toothpaste................................................................................................................................................................17

Recommendations....................................................................................................................................................19

Teeth Brushing Technique........................................................................................................................................20

References................................................................................................................................................................20

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ToothA tooth (plural teeth) is a small, calcified, whitish structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores, also use teeth for hunting or for defensive purposes. The roots of teeth are covered by gums. Teeth are not made of bone, but rather of multiple tissues of varying density and hardness.[1]

Teeth of humans are small, calcified, hard, whitish structures found in the mouth. They function in mechanically breaking down items of food by cutting and crushing them in preparation for swallowing and digestion. The roots of teeth are embedded in the maxilla (upper jaw) or the mandible (lower jaw) and are covered by gums. Teeth are made of multiple tissues of varying density and hardness. [1]

Teeth are among the most distinctive (and long-lasting) features of mammal species. In human the first set (also called the "baby", "milk", "primary", and "deciduous" set) normally starts to appear at about six months of age, although some babies are born with one or more visible teeth, known as neonatal teeth. Normal tooth eruption at about six months is known as teething and can bepainful.[2]

Figure 1: Teeth of humans

Figure 2:Longitudinal section of tooth

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Human Teeth Anatomy

Figure 3:Human Teeth Anatomy

The teeth are the hardest substances in the human body. Besides being essential for chewing, the teeth play an important role in speech. Parts of the teeth include:

1. Enamel: The hardest, white outer part of the tooth. Enamel is mostly made of calcium phosphate, a rock-hard mineral.

2. Dentin: A layer underlying the enamel. Dentin is made of living cells, which secrete a hard mineral substance.

3. Pulp: The softer, living inner structure of teeth. Blood vessels and nerves run through the pulp of the teeth.

4. Cementum: A layer of connective tissue that binds the roots of the teeth firmly to the gums and jawbone.

5. Periodontal ligament: Tissue that helps hold the teeth tightly against the jaw.6. A normal adult mouth has 32 teeth, which (except for wisdom teeth) have erupted by about

age 13:7. Incisors (8 total): The middlemost four teeth on the upper and lower jaws.8. Canines (4 total): The pointed teeth just outside the incisors.9. Premolars (8 total): Teeth between the canines and molars.10. Molars (8 total): Flat teeth in the rear of the mouth, best at grinding food.11. Wisdom teeth or third molars (4 total): These teeth erupt at around age 18, but are often

surgically removed to prevent displacement of other teeth.The crown of each tooth projects into the mouth. The root of each tooth descends below the gum line, into the jaw.[3]

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Typesof TeethThere are 32 permanent teeth including four different tooth types in the mouth.

1. Incisors The incisors at the front of the mouth have a sharp biting surface and are used for cutting or shearing food into small chewable pieces. There are eight incisors in both primary and permanent dentitions.

2. Canines The canines are situated at the 'corners' of the dental arches. They have a sharp, pointed biting surface. Their function is to grip and tear food. There are four canine teeth in both primary and permanent dentitions.

3. PremolarsThe premolars, unlike the incisors and canines, have a flat biting surface. Their function is to tear and crush food. They are unique to the permanent dentition which has eight premolars.

4. Molars  The molars are the largest of the teeth. They have a large flat biting surface. The function of the molars is to chew, crush and grind food. There are eight molars in the primary dentition and twelve in the permanent dentition.[4]

Figure 4: Types of tooth

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Functions of teeth

1. Food needs to be broken down and chewed before entering the digestive system so that our body can easily absorb nutrients from them.

2. Teeth can help us pronounce accurately.3. Teeth can help us look better by giving us a good profile. Deciduous teeth can reserve spaces

for permanent teeth. Once the permanent teeth start to erupt, the deciduous teeth will fall out and give room for permanent teeth.[5]

Common Dental Problems

Dental problems are never any fun, but the good news is that most of them can be easily prevented. Brushing twice a day, flossing daily, eating properly and regular dental checkups are essential in preventing dental problems. Educating yourself about common dental problems and their causes can also go a long way in prevention.[6]

1. Bad BreathBad breath, also called halitosis, can be downright embarrassing. According to dental studies, about 85% of people with persistent bad breath have a dental condition that is to blame. Gum disease, cavities, oral cancer, dry mouth and bacteria on the tongue are some of the dental problems that can cause bad breath. Using mouthwash to cover up bad breath when a dental problem is present will only mask the odor and not cure it. If you suffer from chronic bad breath, visit your dentist to rule out any of these problems.

2. Tooth DecayDid you know tooth decay, also known as cavities, is the second most prevalent disease in the United States (the common cold is first). Tooth decay occurs when plague, the sticky substance that forms on teeth, combines with the sugars and / or starches of the food we eat. This combination produces acids that attack tooth enamel. The best way to prevent tooth decay is by brushing twice a day, flossing daily and going to your regular dental check ups. Eating healthy foods and avoiding snacks and drinks that are high in sugar are also ways to prevent decay.

3. Gum (Periodontal) DiseaseStudies have shown that periodontal disease, also known as gum disease, is linked to heart attacks and strokes. Gum disease is an infection in the gums surrounding the teeth. Gum disease is also one of the main causes of tooth loss among adults. There are two major stages of gum disease: gingivitis and periodontitis. Regular dental check ups along with brushing at least twice a day and flossing daily play an important role in preventing gum disease.

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4. Oral CancerOral cancer is a serious and deadly disease that affects millions of people. In fact, the Oral Cancer Foundation estimates that someone in the United States dies every hour of every day from oral cancer. Over 300,000 new cases of oral cancer are diagnosed every year, worldwide. This serious dental disease, which pertains to the mouth, lips or throat, is often highly curable if diagnosed and treated in the early stages.

5. Mouth SoresThere are several different types of mouth sores and they can be pesky and bothersome. Unless a mouth sore lasts more than two weeks, it is usually nothing to worry about and will disappear on its own. Common mouth sores are canker sores, fever blisters, cold sores, ulcers and thrush.

6. Tooth ErosionTooth erosion is the loss of tooth structure and is caused by acid attacking the enamel. Tooth erosion signs and symptoms can range from sensitivity to more severe problems such as cracking. Tooth erosion is more common than people might think, but it can also be easily prevented.

7. Tooth SensitivityTooth sensitivity is a common problem that affects millions of people. Basically, tooth sensitivity means experiencing pain or discomfort to your teeth from sweets, cold air, hot drinks, cold drinks or ice cream. Some people with sensitive teeth even experience discomfort from brushing and flossing. The good news is that sensitive teeth can be treated.

8. Toothaches and Dental EmergenciesI can't think of much worse than suffering from a toothache. While many toothaches and dental emergencies can be easily avoided just by regular visits to the dentist, we all know that accidents can and do happen. Having a dental emergency can be very painful and scary. Fortunately, you can do several things until you are able to see your dentist.

9. Unattractive SmileWhile an unattractive smile is not technically a "dental problem," it is considered a dental problem by people who are unhappy with their smile and it's also a major reason that many patients seek dental treatment. An unattractive smile can really lower a person's self-esteem. Luckily, with today's technologies and developments, anyone can have a beautiful smile. Whether it's teeth whitening, dental implants, orthodontics or other cosmetic dental work, chances are that your dentist can give you the smile of your dreams.[6]

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Medications Used in Dentistry

There are a number of different drugs, your dentist may prescribe, depending on teeth condition. A description of the most commonly used drugs in dental care is described below. The dose of the drugs and instructions on how to take them will differ from patient to patient, depending on what the drug is being used for, patient's age, weight, and other considerations.[7]

It is important to always communicate all dental signs and symptoms to your dentist, so that appropriate management and choice of medications can be made.

Medications Used-

To control pain (Anethetics, Analgesics, NSAID)To control plaque and gingivitis(Mouth washe)To prevent or treat infections (Antibiotics)Antifungals (Candida)To prevent tooth decay (Flouride)To relieve anxiety (Muscle relaxant)To treat xerostomia (Artificial saliva)

Medication in dentistry

I. Anesthetics II. Pain killers

III. Mouth washeIV. AntibioticsV. Antifungals

VI. AntisepticsVII. Muscle relaxant

VIII. Artificial SalivaIX. Fluoride supplements

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I. AnestheticsAnesthetics are-

Local anesthesiaGeneral anesthesiaNitrous oxideConsiouse sedation: intravenous sedation by Diazepam[7]

Anesthetics Found in the form of

SprayGel (intraoral)Ointments (extraoral)Solutions

Brand name products

ChlorasepticOrajelXylocaine

Used by the patient

To relieve pain or irritation caused by-

ToothacheTeethingCold soresCanker soresFever blistersPain or irritation caused by dentures Pain caused by orthodontics braces

Complications1. Complications associated with absorption of the anesthetic solution1.1. Systemic drug reactions due to the local anesthetic agent:

Toxicity Allergy Anaphylactic reactions Idiosyncrasy

1.2. Local reactions: Infections due to contaminated solutions Local tissue irritation

2. Complications associated with needle insertion-

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PainEdemaInfectionMuscle trismusBroken needlesHematoma formationSloughing and ulcerationBizarre Neurological symptoms[8]

II. Analgesics/pain killers

A. Paracetamol/ AcetaminophenBrand name products

TylenolFevadolPanadolNapa

Indications:

Mild toothacheAfter tooth extractionTeethingmild to moderate pain

DoseAdults:.5–1 g every 4–6 hours.6–12 yars: 250–500 mg every 4–6 hours.1–5 year: 120–250 mg every 4–6 hours.[8]

Contraindication

Renal failure, papillary and tubular necrosis.Asthma, Liver failure

Complications

feeling dizzynauseasleepiness

B. Non-steroidal anti-inflammatory drug (NSAIDs)[8]

IndicationsTooth acheAbscess

Figure 5: Teething

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Acute pain

Examples – COX1 and COX-2 : Ibuprofen, ketorolac, flurbiprofen, ketoprofen, diclofenac, aspirin and – COX-2 : celecoxib ,rofecoxib, and Nimesulide

Dose – 100 mg twice a day.

Complications of NSAIDsDizzinessFeeling lightheadedProblems with balanceDifficulty concentratingMild headaches[9]

C. Corticosteroids ointment

To relieve the discomfort and redness in [8]

1. The palat as in canker sore2. The lip as in fever blister, angular chelitis3. The cheak as in canker sore

OrabaseOralone

III. Mouth washesChlorhexidine mouth wash

Wash to control plaque and gingivitis in the mouth

AntisepticKill the bacteria that cause bad breathStaining of the teeth

Fluoride mouth washSensitive teethUsed for patients with high caries activity

Rinse for 2 minutes / 10 days

ComplicationsStaining of teeth and/or dental restorationsTaste disorder (dysgeusia)Build-up of tartar on the teethMouth and tongue irritation or numbness

Figure 6: Mouth washes

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Mucosal erosionsRetention of sodiumSwollen glands on the side of the face or neckSensitivity of tooth rootsMouth ulcers

IV. Antibiotics

Tetracycline’s (the class of drugs including demeclocycline, doxycycline, minocycline, oxytetracycline, and tetracycline) and the drug triclosan (marketed as Irgasan DP300) are also used in dentistry. These medications may be used either in combination with surgery and other therapies, or alone, to reduce or temporarily eliminate bacteria associated with periodontal disease, to suppress the destruction of the tooth's attachment to the bone or to reduce the pain and irritation of canker sores. Dental antibiotics come in a variety of forms including gels, thread-like fibers, microspheres (tiny round particles), and mouth rinses.[7]

Doxycycline (Vibramycin)

MOA: inhibit protein synthesis by preventing aminoacyl transfer RNA from entering the acceptor sites on the ribosomeDose: 100mg qd-bid x 7-14 daysContraindications:

o Foodo pregnancy

Adverse events: GI Drug interactions: anti-epilepticsPregnancy category DBacteriostaticSpectrum:

o Broad, Gram +, -, anaerobes, aerobes, and spirochetesResistance:

o Widespread, cross resistance Photo Sensitivity

Complications of Antibiotics

Severe watery diarrhoea and abdominal cramps (signs of a serious bacterial infection of the gut - Clostridium difficile infection).Shortness of breath, hives, rash swelling of lips, face, or tongue, fainting Vaginal itching or discharge (signs of vaginal thrush).White patches on the tongue (signs of oral thrush) and bad taste in mouth.Vomiting[10]

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V. Antifungal

Antifungal are prescribed to treat oral thrush. The goal of treatment is to stop the spread of the Candida fungus. Antifungal medicines are available in tablets, lozenges, or liquids that are usually "swished" around in your mouth before being swallowed.[8]

Nystatin:o MOA: inhibit cell wall synthesiso Dose: 5 ml swish and swallow q 4 h x 10-14 do GI upseto Drug interactions: minoro Pregnancy category C

Clotrimazole (Mycelex), ketoconazole (Nizoral), fluconazole (Diflucan) o MOA: inhibit cell wall synthesiso Dose: 200-800 mg qd x up to 12 monthso GI upseto Drug interactions: major p-450 enzyme inhibitor, interactions with many drugso Pregnancy category C

Complications of Antifungal 

loss of appetitevomitingfeeling sick for a long timejaundice – yellowing of your skin or the whites of your eyes unusually dark urine or pale faeces (stools)unusual tiredness or weakness[11]

VI. AntisepticsDentist may recommend the use of an over-the-counter antiseptic mouth rinse product to reduce plaque and gingivitis as well as kill germs, which may be the cause of bad breath.

Knowing the role of supragingival plaque in the initiation of periodontal disease and insufficient control of the plate, the use of antiseptics is warranted. This anti-plaque derived from different chemical classes and has different mechanisms of action.[8]

VII. Dry Mouth DrugsPilocarpine, marketed as Salagan, may be prescribed by your dentist if you have been diagnosed with dry mouth. The drug stimulates saliva production. [8]

VIII. Muscle Relaxants 

Muscle Relaxants may be prescribed to reduce your stress to help you stopgrinding your teeth and to treat temporomandibular joint disorders.E.g. Valium in low dose. [8]

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IX. Drugs to Control Plaque and Gingivitis

Chlorhexidine is an antibiotic drug used to control plaque and gingivitis in the mouth or in periodontal pockets (the space between your gum and tooth). The medication is available as a mouth rinse and as a gelatin-filled chip that is placed in the deep gum pockets next to your teeth after root planing. The drug in the gelatin-filled chip is released slowly over about seven days. Dental products containing this antibacterial are marketed under various prescription-only brand names, such asPeridex, PerioChip, and PerioGard, as well as other over-the-counter trade names.

Complications: Chlorhexidine may cause an increase in tartar on your teeth. It may also cause staining of the tooth, tooth filling, and dentures or other mouth appliances. Brushing with a tartar-control toothpaste and flossing your teeth daily may help reduce this tartar build-up and staining. In addition, you should visit your dentist at least every six months to have your teeth cleaned and your gums examined. Be sure to tell your dentist if you have ever had any unusual or allergic reaction to this medicine or to skin disinfectants containing chlorhexidine. [8]

X. Other dental medications

FluoridesFluoride which is available in most over-the-counter toothpastes, is used to prevent tooth decay. Prescription strength fluoride is also available if prescribed by a physician. [8]

Types of FluoridesF tooth pasteF varnishF mouth rinseF tablets

BenzodiazepinesBenzodiazepines such as diazepam (Valium) is used for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. It works by relaxing the patient during dental procedures such as temporomandibular joint disorders.

Saliva substitutesSaliva substitutes such as Moi-Stir, Mouth Kote, Optimoist, Saliva Substitute, Salivar and Xero-Lube are used for treating dry mouth, an occasional complication of autoimmune diseases or occasionally unassociated with other diseases. They usually come as sprays and are used as needed. [3]

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Dental Prophylactic PreparationsProphylactic means a medicine which preserves or defends against disease or any device or mechanism intended to prevent harmful consequences.[12]

MouthwashMouthwash or mouth rinse is a chemotherapeutic agent used as an effective home care system by the patient to enhance oral hygiene. Some manufacturers of mouthwash claim that antiseptic and anti-plaque mouth rinse kill the bacterial plaque causing cavities, gingivitis, and bad breath. Anti-cavity mouth rinse uses fluoride to protect against tooth decay. It is, however, generally agreed that the use of mouthwash does not eliminate the need for both brushing and flossing. As per the American Dental Association, regular brushing and proper flossing are enough in most cases although the ADA has placed its Seal of Approval on many mouthwashes that do not contain alcohol.

Mouthwash is a liquid solution that is swished around inside the mouth to cover the teeth, gums and tongue, and then is spit out. Some types of mouthwashes help to temporarily mask bad breath (halitosis) as well as rinse the area of debris and bacteria. Others are intended to coat the teeth with fluoride to strengthen them and help prevent decay. Mouthwash may be available in over-the-counter or prescription forms. [13]

Contents

Sorbite, silicon dioxide, polyethyleneglycol, demineralised water, sodium lauryl sarcosinate, flavoring material, sodium monofluorophosphate (fluoride weight fraction 0,1%), papain, sodium carboxy-methylcellulose, stevioside, calcium glycerophosphate, tea tree oil, methyl paraben, propyl paraben, disodium salt EDTA, CI 19140, CI 42090. [13]

Figure 7: Mouthwash

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The Manufacturing Process

Weighing and mixing

1. After transporting the raw materials into the factory, the ingredients are both manually and

mechanically weighed. This ensures accuracy in the ingredients' proportions. Then the ingredients

are mixed together. Usually, the glycerin-water mixture is done first.

2 .All the ingredients are mixed together in the mixing vat. The temperature and humidity of vat are

watched closely. This is important to ensuring that the mix comes together correctly. A commonly

used vat in the toothpaste industry mixes a batch that is the equivalent of 10,000 four-ounce (118

ml) tubes.

Filling the tubes

3. Before tubes are filled with toothpaste, the tube itself passes under a blower and a vacuum to

ensure cleanliness. Dust and particles are blown out in this step. The tube is capped, and the

opposite end is opened so the filling machine can load the paste.

Figure 8: Manufacturing Process

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4. After the ingredients are mixed together, the tubes are filled by the filling machine. To make sure

the tube is aligned correctly, an optical device rotates the tube. Then the tube is filled by a

descending pump. After it is filled, the end is sealed (or crimped) closed. The tube also gets a code

stamped on it indicating where and when it was manufactured.

Packaging and shipment5. After tubes are filled, they are inserted into open paperboard boxes. Some companies do this by

hand.

6. The boxes are cased and shipped to warehouses and stores.

Quality Control

Each batch of ingredients is tested for quality as it is brought into the factory. The testing lab also

checks samples of final product. [13]

Toothpaste 

In our daily activities can not be separated from tooth brushing with a toothbrush and toothpaste. Activities toothbrush should be done 2-3 times a day, mainly carried out after every meal. If ones never once in a day does not brush his teeth, consequently the mouth feel uncomfortable and awkward to talk to someone at close range because worry about bad breath. [14]

When used for toothbrushes, toothpaste that both must satisfy the properties: 

Can remove foreign particles, the remaining food on the teeth, plaque or tartar, and can clean teeth.

It should not toxic, has a sense of fun and feel fresh after using the mouth. [14]

Figure 9: Toothpaste

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The raw material is composed of toothpaste

1. Polishing material (abrasive), is one of the most important ingredient to remove food particles remaining on the teeth. Materials used include aluminum phosphate.

2. Foaming material, serves to assist the action polishing materials by wetting the teeth and food particles left on the teeth and also serve as mucus emulsifier in the mouth. Materials used as foaming agent is SLS (sodium lauryl sulfonate) by trade name texapon, FAME, etc.

3. Materials moistener (moisturizer), serves to prevent drying and hardening of the toothpaste. Materials often used include glycerin, propylene glycol, etc..

4. Binder, serves to prevent separation of ingredients in toothpaste. Materials used include sodium alginate. 

5. Sweetening matter, serves to also write a sweet taste in toothpaste. Materials used include saccharin. 

6. Flavoring agent, serves to provide aroma and flavor in pasta and avoid feeling of nausea. In addition, to increase the freshness of toothpaste. Materials used peppermint oil.

7. Preservative, serves to maintain the physical structure, chemical and biological toothpaste. This material should not toxic. Preservative sodium benzoate used.

8. Fluoride materials, is one substance that serves for the growth and health of teeth, coating the tooth structure and resistance to decomposition process and trigger mineralization. The flour give the effect of detergents and chemical elements harden tooth enamel coating. Fluoride is widely used is one of sodium fluoride (NaF). Provision of fluoride toothpaste is recommended for 0.05% - 0.08%, due to excess of fluoride will cause damage to health. The authors recommend that in making toothpaste without fluoride does not matter. [14]

Composition

1. Aluminum phosphate maximum2. Texapon 3%3. Glycerin (15-20)%4. Sodium alginate 25%5. Saccharin taste6. Peppermint oil to taste7. Sodium benzoate 0.1%8. Sodium fluoride9. Sufficient water

Equipment needed: container and wood stirrer 

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Preparations

1. Sodium alginate + glycerin mix evenly2. (1) + Texapon mix evenly3. Water + Sodium benzoate stir4. (3) is mixed into (2) stir + NaF5. (4) + Sweeteners stir6. (5) + Aluminum phosphate mix7. (6) + Peppermint oil mix8. Ready packaged

RecommendationsTo keep your teeth healthy it is recommended to clean them not less than 2 times a day. Additional use of elixir for the mouth cavity provides even better result. [7]

Reduce sugar intake.Brushing twice a day.Flossing once daily.Use of mouthwash.Healthy snack habit. Proper brushing method

Teeth Brushing Technique

Proper brushing takes at least 2 min.Use short gentle strokes.Make a 45 degree angle between brush and tooth surface .Clean the outer surface of upper teeth , then lower teeth .Clean the chewing surface.Make sure to brush your tongue .[7]

Figure 10:Proper Teeth Brushing Technique

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References

1. http://en.wikipedia.org/wiki/Tooth 2. 2.file:///H:/7th%20Semister/Hospital%20Pharmacy/Human%20tooth%20%20Wikipedia,%20the

%20free%20encyclopedia.htm3. http://www.webmd.com/oral-health/picture-of-the-teeth?page=1 4. http://www.dentalhealth.ie/children/toothdevelopment/types.html 5. http://www.toothclub.gov.hk/en/pnc/en_pnc_2_2_1_5.html 6. http://dentistry.about.com/od/toothmouthconditions/tp/10-Common-Dental-Problems.htm 7. http://www.webmd.com/oral-health/medications-used-dentistry 8. http://www.slideshare.net/iarabii/therapeutics-in-dentistryanalgesics-10308150 9. http://my.clevelandclinic.org/drugs/Non-Steroidal_Anti-Inflammatory_Drugs/hic_Non-

Steroidal_Anti-Inflammatory_Medicines_NSAIDs.aspx10. http://www.patient.co.uk/health/antibiotics-leaflet 11. http://www.nhs.uk/Conditions/Antifungal-drugs/Pages/Side-effects.aspx

12.http://medical-dictionary.thefreedictionary.com/prophylactic

13.http://www.madehow.com/Volume-3/Toothpaste.html 14. http://formulation.vinensia.com/2011/03/toothpaste-formula-composition-and.html