DENTIFRICES – A BRIEF REVIEW ON THE CUTTING EDGE DRUG DELIVERY SYSTEMS

About Authors:
RESHMY RAJAN
DEPT OF PHARMACEUTICS, AMRITA SCHOOL OF PHARMACY,
AIMS HEALTH CARE CAMPUS,
KOCHI 682041

ABSTRACT
Dental diseases are recognized as a major public health problem, in civilized society. The prevalence of tooth decay, various dental diseases, and tooth loss are so great that a permanent healthy oral system in the body is almost impossible. Dental diseases are studied by oral examination of a particular section of the population and the incidence measured by the number of new cases occurring in a given period of time. In UK it is estimated that 99% of children under 12 years suffer from dental caries. Modern dentifrices compositions contain numerous components that have various therapeutic and cosmetic functions. Fluoride was the first of the therapeutic additions to the basic dentifrice formulations. Most of the dental compositions contain an abrasive cleansing agent which aids in the removal of adherent deposits on the teeth. Advertising and taste rather than therapeutic superiority determine the market advantage. During the past decade, however, it has not been enough for a dentifrice to prevent tooth decay or create a smile that will win the man, woman or job of one's dreams. Now, it seems, a dentifrice must fight tartar, plaque and gum disease as well. And manufacturers do not want to forget "niche" consumers -smokers, natural product fans, people with tooth sensitivity, and those with dry mouths. Sustained-release delivery systems allocate extended drug action to treat dental and periodontal diseases compared to the conventional dosage forms. Herbal extracts have been successfully used in dentistry as tooth cleaning and antimicrobial plaque agents. Only two out of ten 5-year old have sound teeth according to the General Dental Council.The present review deals with the various novel formulations of dentifrices.

Reference Id: PHARMATUTOR-ART-1229

INTRODUCTION
White teeth have been popular attributes of beauty in many societies since ancient times. In the Bible, when Jacob blessed his children, he promised Judah teeth whiter than milk. According to Cicero, white teeth are the first requirement of beauty. Literature is replete with allusions to teeth comparable to shining pearls. When nature did not live up to expectations, help was elicited from chew sticks and fiber sticks as natural toothbrushes and from a wide range of dentifrice ingredients including ground animal bones (often burned to produce charcoal), egg shells, pumice or chalk as abrasives admixed with honey, salt, myrrh, cinnamon and/or oils.(1)
Composition of dentifrices
Modern dentifrice compositions contain numerous components that have various therapeutic and cosmetic functions. Most of these compositions contain an abrasive cleansing agent which aids in the removal of adherent deposits on the teeth (2). Herbal extracts have been successfully used in dentistry as tooth cleaning and antimicrobial plaque agents.
Generally the dentifrice ingredients can be subdivided into active ingredients—which yield therapeutic benefits to the patient—and inactive ingredients. An active ingredient is included in a dentifrice to perform a specific preventive or treatment action (Table 1). Approximately 1% to 2% of a dentifrice contains active ingredients. (3)
There are many varieties of toothpaste currently available with varying combinations of ingredients, depending upon the needs that the dentifrice is intended to address. It is important to understand the ingredients in dentifrices, as well as the indications for each dentifrice, in order to make recommendations based upon patients’ clinical status and needs.

ORAL DENTAL DISEASES
Dental caries is an infectious microbiological disease of the teeth that results in localized dissolution and destruction of the calcified tissues. It is the second most common cause of tooth loss and is found universally, irrespective of age, sex, caste, creed or geographic location. It is considered to be a disease of civilized society, related to lifestyle factors, but heredity also plays a role. In the late stages, it causes severe pain, is expensive to treat and leads to loss of precious man-hours. However, it is preventable to a certain extent. The prevalence of dental caries in India is 50%–60 %.( 4)
Dental diseases such as tooth decay and gum disease are two of the most common human diseases. Dry socket is another painful dental problem that may occur after tooth extraction. Other dental problems as orthodontic problems or stained/discolored teeth, although they are mostly cosmetic and not dental health problems, concern an increasing number of people in recent years due to the modern way of life. Some dental problems as bad breath and dry mouth might be symptoms of other serious health problems or systemic diseases. (4)
The most familiar symptom of a tooth problem is toothache. The severity of the pain depends on the level of which part of the tooth is affected and how deeply the decay extends. Tooth decay is a destruction of the tooth enamel. Each tooth has a coating of enamel, which protects the underlying dentine containing soft tissue and nerves. When foods are frequently left on the teeth, bacteria that live in the mouth thrive on these foods and produce acids over a period of time; these acids destroy tooth enamel, resulting in tooth decay. The main diseases of the teeth include plaque, caries and pyorrhea. Proper dental care is necessary for eliminating tooth decay and periodontal diseases. (4)
Dental caries is a localized, transmissible infectious process that ends up in the destruction of hard dental tissue. It results from the accumulation of plaque on the surface of teeth and biochemical activities of complex micro-communities. Streptococcus mutans is one of the main opportunist pathogen of dental caries, which plays a central role in fermenting carbohydrates that result in acid production, leading to the corrosion of tooth enamel. In addition, other micro flora like Lactobacillus species are also associated with active caries lesions. Lactobacillus acidophilus is the most common. Poor oral hygiene is one of the reasons for accumulation of these microbes and their harmful activities. The common method for maintaining good oral hygiene is brushing the teeth with dentifrices that have antimicrobial properties and can prevent the degradation of tooth enamel.
The people living in Indian subcontinent largely depend on the traditional systems for the treatment of toothache, caries and other diseases related to teeth. The traditional herbal preparations for dental care comprise of various types of herbal powders and chewing sticks made out of young woody stem or root pieces.
The given Table 2 depicts some of the plants which are used for oral health by the people of India.
It is compiled from the literature reports. (5)
In the Indian subcontinent the commonest source of chewing sticks is Azadirachta indica. Salvador persica stems and roots are also widely used as chewing sticks. Chewing sticks obtained from A. indica contain essential oils and exert carminative, antiseptic and analgesic action. The tannins of chewing sticks have an astringent effect on mucous membrane.
Fluoride toothpastes that fight cavities have become common. The current competition among products is for the additional benefits they can offer -- with anti-tartar and whitening leading the way. Toothpastes serving special populations have been increasing and now include desensitizing dentifrices, natural toothpastes, smokers toothpastes, and one designed for people with xerostomia. The newest toothpastes are multibenefit products that include among their properties a clinically demonstrated anti-gingivitis effect -- such as Crest Gum Care and Colgate Total, which was recently cleared by the Food and Drug Administration for antiplaque/antigingivitis as well as anticaries effects.(6)

Dentifrices accepted by the ADA(American Dental association) Seal Program are in three general categories -- desensitizing, fluoride and fluoride with tartar control. A variety of other products, such as various whitening products, are being sold but have not applied for nor been granted in the ADA seal. Most dentifrices have similar basic ingredients:
- Abrasives (20 percent to 50 percent)
- Humectants to prevent water loss (20 percent to 40 percent);
- Water (20 percent to 35 percent)
- Binders to stabilize and prevent separation (1 percent to 2 percent);
- Detergents (1 percent to 3 percent)
- Flavors,sweeteners and preservatives (1 percent to 3 percent).(6)

The therapeutic components are the various fluorides; antitartar compounds; and desensitizing, antibacterial and whitening agents. Dentifrices are available as pastes, gels and liquids in tubes or pumps.(6)
Oral administration of antibiotics to treat dental problems mostly yields slow actions due to slow onset and hepatic “first-pass.” Again, commonly used dental paints are generally washed out by saliva within few hours of application. To overcome the challenges, polymeric molds to be placed on an affected tooth (during carries and gum problems) were used for sustained drug release for prolonged local action. These formulations are a novel approach to deliver the drug(s) for a prolonged period for local action upon its application on an affected tooth. The polymeric mold should have an appropriate adhesiveness so that it may be easily fixed on the affected tooth and can be removed easily whenever necessary. (7-10)

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NOVEL FORMULATIONS USED AS DENTIFRICES
Sustained-release delivery systems allocate extended drug action to treat dental and periodontal diseases compared to the conventional dosage forms. Better patient compliance in terms of application frequency, better relief for longer period of time, and reduction in dose of drug leads to overcome the adverse reactions due to higher dose to achieve the same effectiveness when given orally. Besides faster local action as compared to slow onset of action by oral route and avoidance of hepatic “first-pass” effect are important advantages of this formulation. Search of sustained-release devices is a relatively new area in dentistry. Many researches are in progress to develop the similar formulations. Dental gels, mucoadhesive tablets , films , injectable semisolid systems , inserts , and sponges are some of the sustain-release drug-delivery approaches for the treatment of periodontal diseases. However, they are mostly on experimental level. In the future, in root canal treatment and in different gum therapy, this type of dosage form may be very effective. (11-16)
Mouth wash formulations providing long term protection against tooth decay has also developed, by research team at University of Nebraska Medical centre, under the guidance of Dr. Dong Wang, which carries antimicrobial agents directly to teeth. One of the contributing factors to dental cavities is the over population of acid producing bacteria in biofilm that is present on the tooth surface eventually causing dental decay. This formulation would bind to the tooth surface and gradually release antimicrobials against cavity forming bacteria. Recent studies proved that poor dental hygiene leads to heart attack and stroke due to the bacteria having direct access to the blood stream through bleeding gum.(17)
The potential of liposomes as a drug delivery system for use in the oral cavity has also been investigated. Caries and periodontal diseases, such as gingivitis and periodontitis are some of the most prevalent dental ailments in humans. Many pharmaceutical dosage forms have been developed for the local therapy of dental problems and diseases affecting the oral cavity; dentifrices and mouthrinses as the most common. The disadvantage of these conventional systems is the short retention time in the oral cavity because of salivation, the intermittent swallowing, food and beverage intake as well as abrasion by soft tissue movements. Using liposomes as a dental drug delivery system is a new approach that might overcome this problem. Various liposomal formulations have been used as carriers to deliver bactericides to inhibit the growth of biofilms, and in vitro experiments have proven that liposomes adsorb to hydroxyapatite (HA), a commonly accepted model substance for tooth enamel. Liposomes can thus be designed to be bioadhesive, e.g. being retained on enamel surfaces to increase the contact time, thereby prolonging the residence time in the oral cavity.(18-24)
Glass polyalkenoate (‘glass-ionomer’) cements are important dental restorative materials, finding use as liners, and in a variety of other clinical procedures. In addition, they are increasingly finding use in other surgical fields, such as ear, nose and throat surgery. Glass-ionomers have a number of desirable properties in terms of their use in clinical dentistry. They are easy to manipulate, are dimensionally stable, release fluoride, and they adhere naturally to dentine and enamel without recourse to special bonding agents. (24-27)
Synthetic dentifrices commonly used contain chemical agents, which are known to produce harmful side effects on prolonged use Hence, dentifrices that contain extracts of medicinal plants and herbs are becoming popular. One such dentifrice is Arodent™ Gum and Dental paste (IPSA), an herbal formulation that is supposed to possess antiseptic, cariostatic, antibacterial, desensitizing, and gum-tightening properties. It has been claimed to be effective in the prevention of bleeding from gums, pyorrhoea, toothache, as prophylaxis against dental caries, inflamed gums with hemorrhage, and foul smell. The herbal dentifrice Arodent contains extracts of several plants. The antimicrobial activity of plant extracts is due to the presence of secondary metabolites, such as alkaloids, flavonoids, phenolics, polyphenols, quinines, flavones, flavonols, tannins, terpenoids, lectins, polypeptides, proanthocynidins, tannins, and quercetin. Plant extracts provide protection by immune stimulation and do not have any known side effects.(28-30)
Modern dentifrice compositions contain numerous components that have various therapeutic and cosmetic functions. Most of these compositions contain an abrasive cleansing agent which aids in the removal of adherent deposits on the teeth. Particulate matter of specific hardness and certain particle size, shape and structure are utilized as such abrasives. These particles must also be compatible with other toothpaste ingredients and safe for repeated human use. Abrasives that are described in the patent literature and have found commercial application include silica xerogels, hydrated silicas, hydrated aluminas, calcium carbonate, dicalcium phosphate (anhydrous and dihydrate), calcium pyrophosphate, and insoluble sodium metaphosphate. These agents are usually 2 to 30 micrometers (.mu.m) in size. Products of about 10 .mu.m appear to find the most commercial acceptance. Insoluble crystalline materials such as quartz have been found too abrasive for safe use on human teeth. Studies found out that hydrated silica prepared by dehydrating a hydrogel with subsequent rehydration provides excellent abrasive action when formulated in dentifrice compositions. The silica is prepared by forming a hydrogel from a soluble silicate and acid, dehydrating the hydrogel from about 60 to 75% water to about 15% water or less and then rehydrating the silica to about 30% water or more. This rehydrated silica is easily combined with other dentifrice components and provides the desired cleansing abrasiveness.
Dentine sensitivity (DS) is a common condition which affects 8-35% of the population. Both In-Office and Over-the-Counter products have been used in treatment, usually occluding open dentine tubules on the exposed root surface. Currently there appears to be no ideal material which permanently occludes dentine tubules. Bioactive and biocompatible glasses are known to induce osteogenesis in physiological systems and may offer suitable materials for surface reactivity which could theoretically occlude tubules. (31)

Teeth Whitening – A New Formulation Of Science. (32)
The process of making the teeth whitened or brighter is the cosmetic processing called the teeth whitening Process. This type of teeth whitening process is called the Dental Bleaching Process, which has now-a-days become the important processing in the Cosmetic Dentistry. The process of making the teeth look better and bright than earlier, by certain processing technique as available in this scientific world is the teeth whitening process where the teeth is made to shine brighter and also maintained to bring a good dental care every day as a part of good health and hygienic action. This is a cosmetic processing which is the latest formulation of the dental group of researchers to make the teeth look bright and thereby avoid the dental infections at any time. For an example, Baking soda is a best teeth whitening material that is a home based processing methodology that is simple and is considered to be available ingredient at home, at all moments. The modern world of Dental health care has introduced the Effective at-home teeth whitening kit also. Gel bleaching processing is available for the teeth whitening process which causes side effects. The method of rubbing with the Walnut tree bark or with the strawberries in the teeth removes the stains in the teeth. Inside of the Orange peel removes the stains. Potassium Hydroxide got from the hard wood burnt into ashes is a good teeth whitener. Cosmetic dentist, in general is the oral care taker helping the person to improve the dental health aesthetics and the function. In fact, a scientific growth of the medical care in dental care is the formulation of this treatment.

REFERENCES
1. Weinberger BW, The History of Dentistry, Vol 1. CV Mosby Co, St. Louis, 1948, pp 13-40.
2. Rehydrated silica gel dentifrice abrasive Dent, Anthony L.; Derolf, M. Robert; Hertzenberg, Elliot P.
3. Wilkins E. Clinical Practice of the Dental Hygienist. 8th ed. Philadelphia, PA: Lippincott, Williams & Wilkins;1999:387.
4. Oral and dental diseases: Causes, prevention and treatment strategies
5. NASEEM SHAH , NCMH Background Papers•Burden of Disease in India.
6. Almass K., Al-Lafi, Tr., World Health Forum 16:206-210, 1995; Chopra et al., Glossary of Indian Medicinal Plants, 1956; Manandhar N P, J.
Econ. Tax. Bot., 12:408-413, 1997; Rao et al. Ethnobot., 8:88-91, 1996; Rispler-Chaim V, J Royl Asiatic Soc. V2:13-20, 1992 and Sushil Kumar et al. Medicinal Plants in Skin Care, CIMAP, 76-89, 1994).
7. The new tooth pastes, Journal of the California association, Irwin D mandel, DDS
8. Feiglin B. Aspects of dentinal and pulpal pain. Diagnosing dental pain. Ann R Australas Coll Dent Surg. 1994;12:143–152.
9. Carvalho RM, Tay FR, Giannini M, Pashley DH. Effects of pre- and post-bonding hydration on bond strength to dentin. J Adhes Dent. 2004;6:13–17.
10. Marthaler TM. Changes in dental caries 1953-2003. Caries Res. 2004;38:173–181. doi: 10.1159/000077752.
11. Dental Mold: A Novel Formulation to Treat Common Dental Disorders, Soma Ghosh, Gopa Roy, and Biswajit Mukherjee , AAPS PharmSciTech. 2009 June; 10(2): 692–702.
12. Stoltze K, Stellfeld M. Systemic absorption of metronidazole after application of a metronidazole 25% dental gel. J Clin Periodontol. 1992;19:693–697.
13. Perioli L, Ambrogi V, Rubini D, et al. Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease. J Control Release. 2004;95:521–533. doi: 10.1016/j.jconrel.2003.12.018.
14. Ahuja A, Ali J, Rahman S. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: formulation and characterisation. Pharmazie. 2006;61:25–29.
15. Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm. 2000;50:83–99. doi: 10.1016/S0939-6411(00)00086-2.
16. Barat R, Srinatha A, Pandit JK, Ridhurkar D, Balasubramaniam J, Mittal N, Mishra DN. Niridazole biodegradable inserts for local long-term treatment of perodontis: possible new life for an orphan drug. Drug Deliv. 2006;13:365–173. doi: 10.1080/10717540500398126.
17. Ang CY, Samsudin AR, Karima AM, Nizam A. Locally produced bovine bone sponge as a haemostatic agent. Med J Malaysia. 2004;59:149–150.
18. Tech transfer blog
19. D. Steinberg, M. Friedman, Dental drug-delivery devices: local and sustained release applications, Crit. Rev. Ther. Drug Carrier Syst. 16 (1999) 425–459.