NUTRACEUTICAL: A REVIEW

NUTRACEUTICAL: A REVIEW

Sejal Patel

Department of Pharmacognosy, Nootan Pharmacy College, Sankalchand Patel University, Visnagar - 384315, Gujarat, India.

ABSTRACT: Nutraceuticals have received considerable interest because of their presumed safety. The Present article focuses on the need for consuming appropriate diets, health issues surrounding the failure to adhere to the known healthy eating models, development of new nutraceuticals / functional foods/food supplements with novel health benefits, elucidation mechanisms of action of these products, to define and understand the analytical, formulation and regulatory aspects of nutraceutical. This article may act as a tool to abreast of the recent developments in nutraceutical research.

Nutraceutical, Food supplement, Functional food

INTRODUCTION: The word of nutraceutical was derived from words of "nutrition" and "pharma-ceutical and which was coined in 1989 by Dr. Stephen L. Defelice, He was founder and chairman of the Foundation of Innovation Medicine. Nutraceuticals are products derived from food sources that provide extra health benefits, in addition to the basic nutritional value found in foods. Depending on the jurisdiction, products may claim to prevent chronic diseases, like cancer, cardiovascular disease and diabetes improve health, delay the aging process, increase life expectancy, or support the structure or function of the body ¹.

The Reasons for the Shift towards Nutraceuticals are: ^2-6

Increasing numbers of consumers, concerned about healthcare costs.

1. Dissatisfied with pharmaceutical agents in promoting health, are turning to nutraceuticals to improve their health and prevent chronic disease.
2. Health care providers recognizes the fact that our heavily processed food supply, coming from crops grown with chemical fertilizers, pesticides, herbicides, and often genetically modified seeds, lack sufficient nutrients necessary for optimum health.
3. People are believing more in prevention than a cure.
4. People who have chronic diseases and have found no solution in allopathic medicines.
5. Economically challenged patients.

With few exceptions, the U. S. Food and Drug Administration (FDA) has not approved nutraceuticals for health benefits or disease prevention; nonetheless, the manufacturers of nutraceuticals have been touting them as health-promoting agents.

Categories Based on Natural Source: ^{7, 8}

• Carbohydrates & Fiber
• Fat & Essential fatty acids
• Protein
• Minerals like Macrominerals & Trace minerals
• Vitamins
• Water
• Other nutrients like Antioxidants, Phyto-chemicals & Intestinal bacterial flora Recombinant nutraceuticals.

They are simply natural with no changes to the food. The food contains several natural components that deliver benefits beyond basic nutrition, such as lycopene in tomatoes, omega-3 fatty acids in salmon, or saponins in soy.

Dietary Supplements: A Dietary supplement is a product that contains nutrients derived from food products that are concentrated in liquid or capsule form. Dietary supplement products include vitamins, minerals, herbs, or other botanicals, amino acids, and substances such as enzymes and metabolites. Dietary supplements can also be extractor concentrates and may be found in many forms such as tablets, capsules, soft gels, gelcap-sule, liquids, or powders. Dietary vitamin B supplements are typically sold in pill form. With a few well-defined exceptions, dietary supplements may only be marketed to support the function of the body and may not claim to treat a disease or condition,

They are grouped on the Basis of Chemical Constituents:

1. Nutrients
2. Herbals
3. Phytochemicals

Phytochemicals basically are plant nutrients with particular biological activities in supporting human health; they work by the following way.

1. Substrate for biochemical reactions.
2. Cofactors of enzymatic reactions.
3. Inhibitors of enzymatic reactions.
4. Absorbents that bind to and eliminate undesirable constituent in the intestine.
5. Enhance the absorption and stability of essential
6. Selective growth factor for beneficial
7. Fermentation substrate for beneficial
8. Selective inhibitors of deleterious intestinal
9. Scavengers of reactive or toxic
10. Ligands that agonize or antagonize cell surface or intracellular receptors ⁹¹.

2. Probiotic Microorganisms: Metchnikoff coined the term “probiotic. Probiotics’ mean ‘for life’ and are defined as live microorganisms, which when consumed in adequate amounts, it confer a health effect on the host Probiotic are very important nutraceutical for removing the toxic flora from the intestine and maintaining a friendly environment, for example, useful consumption of Bacillus bulgaricus which obtained from yogurt they act to crowd out pathogens, like yeasts, other bacteria and viruses that may otherwise cause disease and develop a mutually advantageous symbiosis with the human gastrointestinal tract. They have an antimicrobial effect through modifying the microflora action, and it preventing adhesion of pathogens to the intestinal epithelium, which necessary for producing a toxic effect and reversing some of the consequences of infection on the intestinal epithelium, such as secretory changes and neutrophil migration. Probiotics can cure lactose intolerance by the production of the specific enzyme (ß-galactosidase); in the selection benchmarks for probiotics, one should consider safety, functional and technological aspects as follows Show a potential health benefit.

Probiotics should have a human origin.

• Commonly gram-positive organisms.
• It can survive after passage through acid and bile.
• Can adherence to the human intestinal cells and grow in the gut.
• It can show antagonist action against pathogenic or carcinogenic bacteria.
• It has clinically proven documented beneficial health effects ⁹.

List of Bacteria and Their Beneficial Effects: ^10-18

3. Nutraceutical Enzymes: Enzymes are an essential part of life, without which our bodies would cease to function. Those people who are suffering from medical conditions such as hypoglycemia, blood sugar disorders, digestive problems, and obesity, eliminate the symptoms by enzyme supplements to their diet. These enzymes are derived from microbial, plant, and animal sources.

4. Prebiotics: Prebiotics” are a more recent addition to our vocabulary and are substances which when consumed are not digested by us. Instead, they act as a nutrient source for the good probiotic bacteria.

This encourages the probiotic bacteria to grow in a favourable environment, which in turn reduces the chances that harmful microorganisms may start to grow in our digestive tract. Inulin is prebiotic that has been widely used in processed foods. Essentially, it is a type of fiber obtained from the roots of plants such as chicory, Jerusalem artichoke and even dandelions ¹⁹.

Non-traditional Nutraceuticals: Artificial foods prepared with the help of biotechnology. They are arranged into.

• Fortified nutraceuticals.
• Recombinant nutraceuticals.

Fortified Nutraceuticals: They are enriched with vitamins, minerals, usually at a range up to 100 percent of the Dietary Reference Intake for that nutrient. It constitutes fortified food from agricultural breeding or added nutrients and/or ingredients added folic acid. Some examples are milk fortified with cholecalciferol used in vitamin D deficiency ²⁰.

Recombinant Nutraceuticals: Preparation of various food materials by fermentation process such as cheese and bread to extract the enzyme which are useful for providing necessary nutrients at an optimum level. The production of probiotics and the extraction of bioactive components by enzyme/fermentation technologies as well as genetic engineering technology, are achieved through biotechnology.

Commercial Nutraceuticals: New molecule is difficult to discover and more expensive and risky than ever before. Many pharmaceutical companies are now trying to manufacture nutraceutical because there is undoubtedly a very huge and growing market. Nutraceuticals cover most of the therapeutic areas, like anti-arthritic, cold and cough, sleeping disorders, digestive disease and prevention of certain cancers, osteoporosis, disease related to cardiovascular like blood pressure, cholesterol control, and pain killers, depression, and diabetes. Recognition of health benefits from the consumption of omega-3 fatty acids rich seafood is one of the most promising developments in human nutrition and disease prevention research in the past three decades.

• Dietary supplements,
• Functional food,
• Medicinal food

Medicinal Food: Medicinal food a food which is formulated to be consumed or administered internally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation also without any components that promote disease condition or contain a specific nutrient that the body cannot normally produce due to specific disease condition. It is prescribed by physicians for various health conditions that lead to impaired ingestion, digestion, absorption, or metabolism of traditional foods like phenyl-ketonuria, coeliac disease, and lactose intolerance ²¹.

Functional Foods: The term was first used in Japan in the 1980s .Functional foods are "any food or food ingredient that may provide a health benefit and disease prevention by adding new ingredients or more of existing ingredients. Consumed as part of a regular diet, Functional foods have been either enriched or fortified, and this process is called nitrification.

In Japan, All Functional Foods have Three Established Requirements:

1. Food should be Present in their naturally occurring form, rather than a capsule, tablet, or powder.
2. Functional food consumed in the diet  as daily
3. (Should regulate a biological process in hopes of preventing or controlling disease ²².

Dietary Fibers are of two Types:

1. Water-insoluble fibers.
2. Water-soluble fibers.

Daily recommended intake is 30-40 gms. Sources: Whole grain cereals, wheat products, Oats, dried beans, legumes.

Table 1: THE BEST HIGH-FIBER FOODS

Antioxidants are of 3 Categories:

1. True antiosxidants.
2. Reducing agents.
3. Antioxidant synergists.

Deficiency causes diseases like Cancers, rheumatoid arthritis, Alzheimer's disease, cardio-vascular diseases.

TABLE 2: EXAMPLES OF ANTIOXIDANT & THEIR SOURCES

Lipids: Fats are highly energy sources for body.

• Saturated fatty acids.
• Monosaturated (MFA).
• Polyunsaturated (PUFA).
• Eicosapentaenoic acid -EPA (20:5 n-3).
• Docosahexaenoic acid - DHA (22:6 n-3).
• Saturated fats- animal based products.
• MFA&PUF plant origin.

Trans fatty acids are products of partial hydrogenation of PU fats and are typically solids at room temperature. MFA & PUFA do not promote the formation of fatty deposits that cannot clog the arteries.

Saturated Fatty Acids: Palmitic, lauric, myristic acids are major cholesterol-elevating fatty acids in our diets. Eskimos diet is rich in cholesterol and fat therefore they are free from heart diseases. Fish rich linolenic acid, found in fish + soyabean oils. Linoleic acid - corn, soy bean oils.

Linolenic Acid- Omega 3 fatty Acids: Linolenic acid (18:3 n-3) 18C, 3 double bonds, the 1^st being at C-3 from the methyl end. CH₃CH₂CH = CHCH₂CH = CHCH₂CH = CH (CH₂)₇ COOH

Precursor of:

• Eicosapentaenoic acid -epa (20:5n-3)
• Docosahexaenoic acid - dha (22:6n-3)[23]

Challenges in Formulation of Nutraceutical Dosage Form:

Analytical Challenges

1. The nutraceuticals are a cluster of a chemical entity, and it is comparatively difficult to identify and quantify all the ingredients in the products.
2. Defining and identifying the impurities and ensuring that these impurities are not harmful to the consumer.
3. Having a Structural Analysis of each entity in a formulation is difficult.

Formulation Challenges:

Tablet Dosage Form:

• Botanicals are complex with multiple chemical components, Can contain up to 50 active. Ingredients; 70- 90% of the formula can be actives.
• There are no of active ingredients and excipients
• Natural Nutraceutical Ingredients challenges which related to particle size, flow, compressibility, moisture sensitivity, in-gredient interaction, content uniformity and quality control (QC) parameter. Botanicals and extracts can vary which based on region the crop was grown, season grown in and other factors.
• Quantity of each ingredient to enable sufficient delivery of the beneficial ingredients, dose size of the active constituent is large hence very less space for excipients in the final formulation. -Nutraceutical formulations normally have more actives ingredient present in higher weights than pharmaceutical formulas. A typical nutraceutical formulation has 70–90% actives ingredient with the balance as excipients, whereas traditional pharmaceutical formulations have 70-90%
• Excipients and 10-30% active ingredient. The fewer excipients and variety of actives in the same formulation make it difficult to achieve certain desired outcomes, like disintegration time, hardness, and friability parameter.
• Careful design of the tablet shape and form needs to be considered when choosing suitable tooling-Adding to the challenge; many nutraceutical tablets tend to be produced using neutral colors such as browns and greys with mottled, textured or granular appearances, which can make any embossing difficult to read.
• The addition of natural ingredients in nutraceuticals, which have a tendency to be unrefined, abrasive, corrosive, and hard, which results in the utilize components damage during the process.

Liquid Dosage Form: Most of nutraceuticals are phytoconstituents, fatty acids, flavonoids, volatile oils etc., Problems faced by these ingredients are.

1. Solubility of these ingredients. Example: carotenoids.
2. Stability of these ingredients. Example: Coenzyme Q10, Omega 3 fatty acids. The oral delivery of probiotics is a slowdown by the low instability of the bacteria in the GIT and consequent of loss of viability under the effect of high acidity and bile salt concentrations.
3. Bioavailability and permeability of these ingredients. Example: Curcumin. Even the bioavailability of the lipophilic antioxidant coenzyme Q10 was challenged by its.
4. Low aqueous solubility and slow dissolution rate in GI fluids which furnished by its highly lipophilic character (log P=21).
5. And permeability is limited by its large molecular weight (863),
6. P-glycoprotein efflux and active transport by a number of transporters (including peptide transporters (PEPT1), cation/camitine tran-sporters (OCT1, OCTN1, OCTN2 and OCT3) and organic anion transporters (AE2 and MCTl) ²⁴

Interactions:

1. Active constituent and excipient interaction.
2. Active constituent and Active constituent interaction.
3. Processing challenges: Large variation in heat, light, and moisture sensitivity of ingredients within one formula. Example in Probiotic encapsulation technology Conditions that maintain cell viability like.
4. Biomaterial selection-natural and synthetic polymers are used; factors to be addressed are:
5. Physicochemical properties like chemical composition, morphology, mechanical strength, stability in GI fluids.
6. Toxicity assay.
7. Manufacturing and sterilization processes.
8. Solvent type and.
9. Toxicity and.
10. Choice of proper technology.

Psychological Challenges: Nutraceuticals manu-facturers must first separate the products and treat nutraceuticals differently from functional foods.

• Tailoring products to domestic tastes and preferences. It includes vegetarian, Hindu dietary practices, traditional remedies, flavor and formulation preferences which reflecting social and cultural diversity.
• Choice of Study Population is difficult. (Based on age, disease condition ) ²⁵

Regulatory Challenges:

1. Need to furnish adequate information with scientific evidence to prove that the product is safe, reproducible, and therapeutically efficient and whether it offers such effects for a definite period of time, say two or three years.
2. The need is to create a mechanism to prove that the product quality is reproducible, and this mechanism needs to be in place with solid, scientific support experimentally that can be proved using a reliable technique.
3. Certification requirements often apply to excipients as well as active ingredients.

• GMO-Free
• Halal
• Kosher
• WADA Compliance (World Anti Doping Agency) country and product-specific

Gamma Terpinene

Registration Category / Classification:

• According to ingredients, the formula may fit into different categories by country.
• Registration complexity varies by category and country; dossier requirements vary greatly.
• Testing requirements for finished products, as well as ingredients and excipients, are not uniform.

Product Gamma Terpinene:

IUPAC Name: 1-Methyl-4-(1-methylethyl)-1, 4-cyclohexadiene.

Plant Sources:

• Cuminum cyminum.
• Melaleuca alternifolia.
• Cannabis sativa.
• Origanum syriacum.

Uses:

1. Antibacterial, Antifungal, Analgesic, Anti-inflammatory, Antioxidant & spasmolyticis.
2. Gyamma terpinene is a perfume and flavoring chemical used in the cosmetics and food industries.
3. Its use in both the pharmaceutical and the electronics semi-conductor manufacturing industries has also proven to be valuable.

Formulation Still Now:

• Cold gel.
• Essential oils.
• Unasni kulzam.

TABLE 3: FORMULATION OF GYAMMA TERPINENE ^26-32

Product Name:

Lycopene IUPAC Name: 2, 6, 10, 14, 19, 23, 27, 31 – Octamethyldotriaconta - 2, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 30 – tridecaene.

Lycopene

Biological Source: Lycopene from the neo-latin lycopersicum, the tomato species.

Other Sources: Carrots, watermelons, gac and papayas, although not in strawberries, or cherries.

Uses:

1. Treatment of the leukopkia (oral cancer),
2. Anticancer and antidiabtic activity,
3. Antioxidant action

Formulation Still Now:

1. Mucoadhesive film
2. Noisome
3. Emulgel
4. Osmotical control capsule
5. Powder (confectionary)
6. Microemulsion

 TABLE 4: FORMULATION OF LYCOPENE: ^33-38

Aloein

3. Product name:

Aloein Biological Sources: Scientific names given to include.

• Aloe perryi,
• Barbadensis,
• Ferox, and
• Hybrids of A. ferox with A. africana and A. spicata.

Uses: It is used as a stimulant-laxative, Treating constipation by inducing bowel movements.

Formulations till now:

• Chewing gum
• Gel
• Gel powder
• Suppositories
• Cosmetic herbal hydrogel

 TABLE 5: FORMULATIONS OF ALOEIN ^39-44

4. Product Name:

Safranal Biological Source: Is a spice derived from the flower of Crocus sativus, commonly known as the "saffron crocus".

IUPAC Names: 2, 6, 6-trimethyl-1, 3-cyclohexadiene-1-carboxaldehyde.

Natural Sources:

• Microcystis (Cyanobacterium)
• Aspalathus linearis (Rooibos)
• Camellia sinensis (Tealeaf)
• Crocus sativus (Saffron)
• Ficus carica (Fig leaf)
• Lycium chinense (Wolfberry)
• Cuminum cyminum (Cumin Seed)
• Centaurea sibthorpii
• Centaurea amanicola
• Centaurea consanguinea
• Erodium cicutarium (common stork's-bill or pinweed)
• Calycopteris floribunda (Ukshi)
• Sambucus nigra (elderberry)
• Citrus limon (lemon)

Safranal

TABLE 6: FORMULATIONS OF SAFRANAL ^44-48

β- Carotene

 5. Product Name:

Beta-carotene Natural Sources:

• Yellow-orange, Green leafy fruits Vegetables (such as carrots, spinach, lettuce, tomatoes, sweet potatoes, broccoli, Cantaloupe, and winter squash).
• In general, the more intense the color of the fruit or vegetable the more beta-carotene it has.

IUPAC Name: 1, 3, 3-Trimethyl-2-[3, 7, 12, 16-tetramethyl-18-(2, 6, 6-trimethylcyclohex-1-en-1-yl) octadeca-1, 3, 5, 7, 9, 11, 13, 15, 17-nonaen-1-yl] cyclohex-1-ene

Uses: Beta-carotene is an antioxidant.

Therapeutic Uses: Prevention of heart disease or cancer.

• Treatment of Sun Sensitivity,
• Age-related Macular Degeneration,
• Metabolic Syndrome,
• Oral leukoplakia,
• Scleroderma

TABLE 7: FORMULATIONS OF β-CAROTENE ^49-53

6. Product Name:

Lutein Biological Source: Lutein is synthesized only by plants, and, like other xanthophylls is found in high quantities in green leafy vegetables such as spinach, kale, and yellow carrots.

IUPAC Name: βε-carotene-3, 3'-diol.

Uses: Many people think of lutein as “the eye vitamin. They use it to prevent eye diseases, including age-related macular degeneration (AMD), cataracts, and retinitis pigmentosa.

Formulations Still Now:

• Lutein nanosuspension converted into pellets and filled into hard gelatin capsules.
• Matrix beadlet
• Cream
• Nanoemulsion
• Lutein softgel
• Self-emulsifying phospholipid suspension

Lutein

TABLE 8: FORMULATIONS OF LUTEIN ^54-58

7. Product Name:

Caryophyllene Biological Source: Caryophyllene or (−)-β-caryophyllene, is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum (cloves), the essential oil of Cannabis sativa, rosemary.

IUPAC Name: (1R, 4E, 9S)-4, 11, 11-Trimethyl-8-methylidenebicyclo [7. 2. 0] undec-4-ene.

Natural Sources:

• Cannabis, hemp, marijuana (Cannabis sativa)
• Black caraway (Carum nigrum)
• Cloves (Syzygium aromaticum)
• Hops (Humulus lupulus) Oregano (Origanum vulgare)
• Black pepper (Piper nigrum) Lavender (Lavandula angustifolia)
• Rosemary (Rosmarinus officinalis)
• Malabathrum (Cinnamomum tamala)
• Ylang-ylang (Cananga odorata)
• Copaiba oil (Copaifera spp.)

Caryophyllene

TABLE 9: FORMULATIONS OF CARYOPHYLLENE ^59-61

8. Product Name:

Pinene Biological Source: Alpha-pinene appears in conifers and numerous other plants. Pinene is a major component of the essential oils of Sideritis spp. (ironwort) and Salvia spp. (sage). Cannabis also contains alpha-pinene. Resin from Pistacia terebinthus is rich in pinene.

IUPAC Name: (1S, 5S)-2, 6, 6-trimethylbicyclo 3, 1, 1 hept-2-ene.

Uses:

• Anaesthetic, antifungal, antiseptic and antibacterial.
• In the chemical industry, selective oxidation of pinene with some catalysts gives many compounds for perfumery
• Pinenes are the primary constituents of turpentine.
• Pinene has also been used as an anti-cancer agent in Traditional Chinese medicine,
• Also for its anti-inflammatory, antiseptic, expectorant and bronchodilator properties.

Formulations till Now:

• Unani formulation zinda tilismath.
• Essential oil.
• Conventional insecticide.

Pinene

TABLE 10: FORMULATIONS OF PINENE ^62-67

9. Product Name:

Sylamarine Biological Source: Silybum marianum has other common names include Cardus marianus, milk thistle, blessed milk thistle, Marian thistle, Mary thistle, Saint Mary's thistle, Mediterranean milk thistle, variegated thistle, and Scotch thistle Asteraceae family.

IUPAC Name: (2R, 3R)-3, 5, 7-trihydroxy-2-[(2R, 3R) - 3 - (4-hydroxy-3- methoxyphenyl) - 2 (hydroxymethyl) - 2, 3-dihydrobenzo[b] [1, 4] dioxin-6-yl] chroman-4-one.

Uses:

• Milk thistle has also been known to be used as food.
• Silibinin is under investigation to see whether it may have a role in cancer treatment (e.g. Due to its inhibition of STAT3 signaling).
• Silibinin also has a number of potential mechanisms that could benefit the skin. These include chemoprotective effects from environ-mental toxins, anti-inflammatory effects, protection from UV induced photocarcino-genesis, protection from sunburn, protection from UVB-induced epidermal hyperplasia and DNA repair for UV induced DNA damage.

Formulations till Now:

Sylimarine:

• Gel
• Floating tablet
• Solid dispersion tablets
• Floating microspheres

Sylimarine

TABLE 11: FORMULATIONS OF SYLIMARINE ^68-72

Geraniol

10. Product Name: Geraniol: Biological source: is a monoterpenoid and an alcohol. It is the primary part of rose oil, palmarosa oil, and citronella oil (Java type). It also occurs in small quantities in geranium, lemon, and many other essential oils.

IUPAC Name: (Z)-3, 7-Dimethyl-2, 6-octadien-1-o.

Uses: Research has shown geraniol to be an effective plant-based mosquito repellent.

Formulations till Now:

• Essential oil
• Carbopol
• gels

TABLE 12: FORMULATIONS OF GERANIOL ^73-75

11. Product Name:

Eugenol IUPAC Name: 1 - Methyl - 4 - (1 -methylethyl) - 1, 4 - cyclohexadiene.

Uses: Eugenol is used in perfumes, flavorings, and essential oils. It is also used as a local antiseptic and anesthetic.

Formulations till Now:

• Permeation enhancer.
• Antibacterial, local analgesic and anaesthetic

Eugenol

TABLE 13: FORMULATIONS OF EUGENOL ^76-79

Limonene

12. Product Name:

Limonene Biological Source: Limonin is enriched in citrus fruits and is often found at higher concentrations in seeds, for example, orange and lemon seeds. Limonin is also present in plants such as those of the Dictamnus genus.

IUPAC Name: 1- Methyl - 4 - (1 - methylethenyl) - cyclohexene.

Uses:

• Limonene is common in cosmetic products
• D-limonene is used in food manufacturing and some medicines
• It is also used as a botanical insecticide
• Limonene is increasingly being used as a solvent for cleaning purposes.
• As it is combustible, limonene has also been considered as a biofuel

Formulations till Now:

• Invasomes
• Transdermal patch

TABLE 14: FORMULATIONS OF LIMONENE ^80-84

REGULATORY AGENCIES FOR NUTRACEUTICALS ^85-89

VARIOUS SCHEDULES FOR FOOD AND NUTRACEUTICALS ⁸⁹

CONCLUSION: Nutraceuticals provide all the essential substances that should be present in a healthy diet for the human. From the above study, it can be concluded that various chemical constituents from natural sources can be obtained and prepared into various optimized, safe, stable formulations for the treatment and diagnosis of diseases. Nutraceuticals are widely used in the food and pharmaceutical industries. Most of the nutraceuticals are from either mineral origin, animal origin or vegetable origin like gamma terpinenes, beta carotene, curcumine, limonene, eugenol, pinene, safranal, geraniol, aloine, caryophylline, licopine and sylimarine.

These constituents are prepared into dosage forms as topical, oral, etc. viz. creams, lotions, ointments, emulsions, unani formulations, aromatic oils, microemulsions, SMEDDS, beads, tablets, emul-gels, herbal formulations etc. used in various categories as antidiabetic, antibiotic, antimicrobial, anti-inflamatory, anti cancer, protective, etc. results of study indicate that demand and consumption of nutraceuticals are now going on increasing due to safety, therapeutic efficacy, stability of formu-lations.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: Nil

REFERENCES:

1. Singh J and Sinha S: Classification, regulatory acts and applications of nutraceuticals for health: a review. International Journal of Pharmacy and Biological Sciences 2012; 2(1): 177-87.
2. Smarta RB: Paradigm shift from pharmaceuticals to nutraceuticals, Nuffoods Spectrum. 2017http://www. nuffoodsspectrum.in/inner_view_single_details. php?page=4&content_type=&vrtcl_panel_nm=&ele_id=NOR_589314edba5a36. 92526952&contentPage=3.
3. Maxwell J: Denis Smith, Mike Brewster, Susan Eggleton, Food as pharma as wellness products evolve, the distinction between food and medicine blurs. R&C worlds express 2012. http://www. pwc. Com/gx/en/retail-consumer/pdf/rc-worlds-newsletter-foods-final. Pdf.
4. Biotech for Wellness: Driving Successful R & D and Licensing in Nutraceuticals through New Business Models and Collaboration, Research and Markets, May 27, 2010, http://www.businesswire.Com/news/home/20100527005898/en/Research-Markets-Biotech-Wellness-Driving-Successful-Licensing.
5. Kumar P, Kuma Nr and Omer T: Nutraceuticals- critical supplement for building a healthy India, World Journal of Pharmacy and Pharmaceutic Sciences 2016; 5(3): 579-94.
6. Olaiya CO, Soetan KO and Esan A: The role of nutraceuticals, functional foods and value added food products in the prevention and treatment of chronic diseases M. 1, African Journal of Food Science 2016; 10(10): 185-93.
7. Shinde N, Bangar B, Deshmukh S and Kumbhar P: Nutraceuticals: a review on current status. Research J Pharm and Tech 2014; 7(1): 110-13.
8. Kharb S and Singh V: Nutriceuticals in health and disease prevention. Indian J Clin Biochem 2004; 19(1): 50-53.
9. Vouloumanou EK, Makris GC and Karageorgopoulos DE: Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrob Age 2009; 34: 1-10.
10. http://probiotics. org/l-casei/
11. Bennett A: List of Probiotic Bacteria 2015, http: //www. livestrong.com.
12. Sanders EM: Food Technology 1999; 53(11): 67-78.
13. Soccol CR: Luciana porto de souza vandenberghe, michele rigon spier, adriane bianchi pedroni medeiros, caroline tiemi yamaguishi, juliano de dea lindner, ashok pandey and vanete thomaz-soccol the potential of probiotics: a review. Food Technol Biotechnol 2010; 48(4): 413-34.
14. Parvez S, Malik KA, Ah Kang S and Kim HY: Probiotics and their fermented food products are beneficial for health, Journal of Applied Microbiology 2006; 100(6): 1171-85.
15. Guerra PN, Bernárdez FP, Méndez J, Cachaldora P and Castro CL: Roduction of four potentially probiotic lactic acid bacteria and their evaluation as feed additives for weaned piglets. Anim Feed Sci Technol 2007; 134: 89-07.
16. Wu ZJ, DU X and Zheng J: Role of Lactobacillus in the prevention of Clostridium difficile-associated diarrhea: A meta-analysis of randomized controlled trials. Chin Med J (Engl.) 2013; 126: 4154–61.
17. Chen X, Kokkotou EG, Mustafa N, Bhaskar KR, Sougioultzis S and O'Brien M: Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in-vitro and in-vivo and protects against Clostridium difficile toxin A-induced enteritis, J Biol Chem 2006; 281: 24449-54.
18. Maia OB, Duarte R, Silva AM, Cara DC and Nicoli JR: Evaluation of the components of a commercial probiotic in gnotobiotic mice experimentally challenged with Salmonella enterica subsp. enterica ser. Typhimurium, Vet. Microbiol 2001; 79(2): 183-89.
19. Montrose DC and Floch MH: Probiotics used in human studies. J Clin Gastroenterol 2005; 39(6): 469-84.
20. Hugenholtz J, Smid JE, Ladero V and Hols P: Metabolic engineering of lactic acid bacteria for the production of nutraceuticals. Antonie Van Leeuwenho 2002; 82: 217-35.
21. Borkar N, Saurabh SS, Rathore KS, Pandit A and Khandelwal KR: An insight on nutraceuticals. Pharma Tutor 2015; 3(8): 13-23.
22. Zou L, Zhang R, Salvia-Trujillo L, Kumosani T and Xiao H, Enhancing Nutraceutical Performance Using Excipient Foods: Designing Food Structures and Compositions to Increase Bioavailability David Julian McClements. Comprehensive Reviewsin Food Science and Food Safety 2015; 14: 824-47.
23. International Food Information Council. Functional Foods Fact Sheet: Omega-3 Fatty Acids http://www.foodinsight. org/Functional_Foods_Fact_Sheet_Omega_3_Fatty_Acids
24. Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach. United Kingdom: John Wiley & Sons, 2006: 187-97.
25. https://www. Nutraceuticalbusinessreview.
26. com/technical/article_page/Overcoming_problematic_production_issues_in_nutraceutical s/98237
27. Zaki NM (2014) Progress and Problems in Nutraceuticals Delivery. J Bioequiv Availab 6: 075-077. doi: 10. 4172/jbb. 10000183
28. Moghimipour E, Aghel N, Mahmoudabadi AZ, Ramezani Z and Handali S: “Preparation and Characterization of liposomes containing essential oil of eucalyptus camaldulensis leaf, Jundishapur Journal of Natural Pharma Products 2012; 7(3): 117-22.
29. Athikomkulcha S, Rith W Panida T: The development of anti-acne products from Eucalyptus globulus and Psidium guajava Journal Health Resource 2008; 22(3): 109-13.
30. Seth NW:The Use of two new formulations of Ocimum canum Sims and Cymbopogon schoenanthus In the control of amitermes evuncifer silvestri (termitidae: termitinae), in togo. International Journal of Natural Sciences Research 2014; 2(10): 195-05.
31. Kumar KA and Choudhary RK: “Determination of antibacterial, antifungal activity and chemical composition of essential oil portion of unani formulation kulzam”, International J of Green Pharmacy 2011; 5(1): 28-33.
32. Desai H, Sav A, Amin P: Formulation and evaluation of mucoadhesive anti-infective solution containing solubilised tea tree oil for vaginal infections. International Journal of Advances in Pharmacy Biology and Chemistry, 2013; 2(2): 385-89.
33. Chalamaiah M and Sharma K: Novel encapsulation of Lycopene in noisome & assessment of its anticancer activity. Journal of Bioequivalence and Bioavailability 2016; 8(5):224-32.
34. Kumari, Singh A, Saurabh SS, Rathore KS and Israni R: Formulation and evalution of Lycopene emulgel”, Indo Ameri J of Pharmaceutical Sciences 2015; 2(6): 1013-27.
35. Jain N, Sareen R, Mahindroo N and Dhar KL: Development and optimization of osmotically controlled asymmetric membrane capsules for delivery of solid dispersion of lycopene. The Scientific World Journal 2014; 438528, 7 pages, 2014. doi:10.1155/2014/438528.
36. Soma S: Development & evaluation if the antioxidant activity of tomato based confectionary. Internationa Food Journal 2013; 20(6): 3167-70.
37. Luciana B, Vande HL, Venugopal V and Stanay: Topical delivery of Lycopene using microemulsion. Willay Science Journal 2010; 99(3): 1346-57.
38. Divyen S, Gaud RS, Mishra A and Nparkin R: Formulation of water soluble mucoadhesive film of lycopene. International Journal of Pharmaceutical Science and Research 2010; 2(1): 06-10.
39. Aslani A and Ghannadi A: Design formulation and evaluation of Aloe vera chewing gum. Journal of Advanced Biomedical Research 2015; 4: 175-82.
40. Ahmad JF, Barkata MA and Javedahmada D: Formulation design of micronized silver sulfadiazine containing aloe vera gel for wound healing. Current Bioactive Compounds 2016; 12(2): 63-68.
41. Suseem SR, Ojhakhyati and Shenoyvranda: Formulation and evaluation of hydrogel with ascorbic acid using Aloe vera gel powder as a drug carrier. Innovare journal of science 2013; 1(1): 18-20.
42. Tarkase KN and Danve AV: Formulation evaluation and in-vitro drug release characteristics of Aloe vera herbal suppositories. Scholars Resear Library 2015; 7(2): 310-16.
43. Pounikar Y, Jain P, Khurana NK, Omray and Patil S: Formulation and characterization of Aloe vera cosmetic herbal hydrogel. International Journal of Pharmacy and Pharmaceutical Sciences 2012; 4(4): 85-86.
44. Khameneh B, Halimi V, Jaafari MR and Shiva Golmohammadzadeh S: Safranal-loaded solid lipid nanoparticle. Iranian Journal of Basic Medical Sciences 2015; 18(1): 58-63.
45. Shilpa CP, Nitin B, Sadhanas K and Mukesh RP: Development of safranal niosomal in-situ nasal gel formulation. World Journal of Pharmaceutical Research 2015; 7(1): 13-21.
46. Zadeh SG: Preparation, characterization & evaluation of sun protective &moisturizing effects of nanoliposomes containing safranal. Iranian Journal of Basic Medical Sciences 2011; 14(6): 521-33.
47. Pooriashakoori, Wunwisakrasaekoopt: Microencapsulation of saffron (Crocus sativus) Extract in copolymer complexes using extrusion method. Chiang mai University Journal of Natural Sciences 2015; 14(1): 53-71.
48. Jaafari RM: Characterization & anti-tumor activity of pegylated nanoliposomes containing safranal in mice bearing c26 colon carcinoma. International J of Pharmaceut Sciences and Research 2016; 7(11): 4379-86.
49. Singh BB, Shakil NA, Kumar J, Walia S and Kar A: Development of slow release formulations of β-carotene employing amphiphilic polymersand their release kinetics study in water and different ph conditions. Journal of Food Science and Technology 2015; 52(12): 8068-76.
50. Ariviani S, Anggrahini S, Naruki S and Raharjo S: Characterization and chemical stability evaluation of β-carotene microemulsions prepared by spontaneous emulsification method using vco and palm oil as oil phase. International Food Research Journal 2015; 22(6): 2432-39.
51. Erna Wulandari, Adella Clara Alverina, Ronny Martien: snedds (self- nanoemulsifying drug delivery system) formulation of carotene in olive oil (Olea europaea)”, International J of Advanced Resear 2016; 4(11): 1031-43.
52. Kar HK: Efficiency of beta-carotene topical application in Melasma-an open clinical trial. Indian J Dermatol venereal Leprol [serial online] 2003 [cited2017 Jul 7]; 69: 92-4. Available from: http://ijdvl. Com / tex. Asp. 2003/69/2/92/5884.
53. Oliveira RGA, Lucia De Carvalho MJ, R. Marília Nutti L, De Carvalho JV and Fukuda WG: Assessment and degradation study of total carotenoid and ß-carotene in bitter yellow cassava (Manihot esculenta crantz) varieties. African Journal of Food Science 2010; 4(4): 148-55.
54. Shegokar KMR, Gohla S, Snselmi C and Müller HR: Lutein nanocrystals as antioxidant formulation for oral and dermal delivery”, International Journal of Pharmaceutics 2011; 420(1): 141-46.
55. Evans M, Beck M, Elliott J, Stephaneetheve, Richard R: Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, Comparative, single-dose study in healthy subjects. European Journal of Nutrition 2013; 52(4): 1381-91.
56. Kale S, Bhandare S and Gaikwad M: Formulation and in-vitro evaluation for sun protection factor of lutein ester extracted from Tagetes erecta Linn flower (family asteraceae) sunscreen creams. Research Journal of Pharmaceutical Biological and Chemical Sciences 2011; 2(3): 947-55.
57. Mitri K, Shegokar R, Gohla S, Anselmi C, Rainer H: Müller, lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. International Journal of Pharmaceutics 2011; 414(1–2): 29, 267-75.
58. Tanumihardjo SA, Jialiang L, Dosti MP: Lutein absorption is facilitated with cosupplementation of ascorbic acid in young adults. Journal of the American Dietetic Association 2005; 105(1): 114-18.
59. Shanmugam S, Park J, Kim KS, Piao ZZ, Yong CS, Choi GH and Woo JS: Enhanced bioavailability and retinal accumulation of lutein from self-emulsifying phospholipid suspension (SEPS). International Journal of Pharmaceutics 2011; 412(1-2): 99-05.
60. Schmitt D, Levy R and Carroll B: Toxicological evaluation of β-Caryophyllene oil. International Journal of Toxicology 2016; 35(5): 558-67.
61. Heuskin S, Lorge S, Lognay G, Wathelet J, s Béra F, Leroy P, Haubruge E, Brostaux Y: A Semiochemical Slow-release formulation in a biological control approach to attract hoverflies. Journal of Environment and Ecology 2012; 3(1): 72-85.

Edris E and Malone CFR: Preferential solubilization behaviours and stability of some phenolic-bearing essential oils formulated in different microemulsion systems. International Journal of Cosmetic Science 2012; 34(5): 441-50.

1. 62. Pieri: Use of β-caryophyllene to combat bacterial dental plaque formation in dogs. BMC Veterinary Research 2016; 12(216): 1-8.
   63. Khokra SL, Prakash O, Jain1 S, Aneja KR, Dhingra Y: Essential oil composition and antibacterial studies of Vitex negundo Extracts.Indian Journal of Pharmaceutical Sciences 2008; 70 (4): 522-26.
   64. Kumar KA, Choudhary KR, Anand DY, Vidya B and Solomon R: Determination of chemical composition of essential oil portion of reputed marketed unani formulation zinda tilismath. International Journal of Pharmacy and Pharmaceutical Sciences 2011; 3(3): 67-68.
   65. Alviano DS: Biological activities of -pinene and β-pinene enantiomers. Molecular Diversity Preservation International 2012; 17(6): 6305-16.
   66. Dai J, Zhu L, Yang L and Qiu J: Chemical composition, antioxidant and antimicrobial activities of essential oil from wedelia prostrate. Experimental and Clinical Sciences International Online Journal 2013; 12: 479-90.
   67. Shuaib M, Ali M, Ahamad J, Naquvi JK, Ahmad MI: Pharmacognosy of pinus roxburghii: a review.Journal of Pharmacognosy and Phytochemistry 2013; 2(1): 262-68.
   68. Dhumal T and Waghmare J: Essential oils: a perfect solution for headlice. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2014; 5(3): 1486-04.
   69. Khan P, Thube R and Arab R: Formulation development and evaluation of silymarin gel for psoriasis treatment. Journal of Innovations in Pharmaceuticals and Biological Sciences 2014; 1(1): 21-26.
   70. Reddy RBD, Malleswari K and Narayana L: Formulation and in-vitro evaluation of silymarin floating matrix tablet. International Journal of Pharmacy and Pharmaceutical Science 2012; 4(5): 468-72.
   71. Nakhat PD: Design and evaluation of sylamarin hp-beta-cyclodextrin solid dispersion tablets. Indian Journal of Pharmaceutical Science 2007; 69(2): 287-89.
   72. Kumar VD: Hepatoprotective activity of silymarin floating drug delivery system against anti tuberculosis drug. International Journal of Pharmacy & Technology 2010; 2(2): 233-44.
   73. Garg R and Gupta GD: Gastroretentive floating microspheres of silymarin: preparation and in vitro evaluation. Tropical Journal of Pharmaceutical Research 2010; 9(1): 59-66.
   74. Bruna Fernanda Murbach Teles Andradem: Cymbopogon martinii essential oil and geraniol at noncytotoxic concentrations exerted immunomodulatory/anti-inflammatory effects in human monocytes. Journal of Pharmacy and Pharmacology 2014; 66(10): 1491-96.
   75. Arumugam MK: Geraniol, a component of plant essential oils a review of its pharmacological activities. International Journal of Pharmacy and Pharmaceutical Sciences 2013; 1(5): 416-20.
   76. Arellao, Santoyo SC, Martina P, Ygartua: Enhancing effect of terpenes on the in-vitro percutaneous absorption of diclofenac sodium. International Journal of Pharmaceutics 1996; 130(1): 141-45.
   77. Nagaich U, Pal AK, Bharti C and Gulat N: Formulation and evaluation of nutraceutical tablet using herbal drugs by direct compression method. Journal of Drug Delivery & Therapeutics 2014; 4(2): 47-51.
   78. Sheth SN and Mistry RB: Formulation and evaluation of transdermal patches and to study permeation enhancement effect of Eugenol. Journal of Applied Pharmaceutical Science 2011; 01(03): 96-101.
   79. Al-okbi Sahar Y, Doha M, Thanaa EH, Edris EA: Protective effect of clove oil and eugenol microemulsions on fatty liver and dyslipidemia as components of metabolic syndrome. Journal of Medicinal Food 2014; 17(7): 764-71.
   80. Jendresen MP and Phillips WR: A comparative study of four zinc oxide and eugenol formulations as restorative materials. The J of Prosthet Dentistry 1969; 21(3): 300-09.
   81. Jadhav KB, Khandelwal RK, Ketkar RA and Pisal SS: Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Development and Industrial Pharmacy 2004; 30(2): 195-203.
   82. Duangjit ACS, Nimcharoenwan BT, Chomya N, Locharoenrat BN and Ngawhirunpat T: Design and development of optimal invasomes for transdermal drug delivery using computer program. Asian Journal of Pharmaceutical Sciences 2016; 52-53.
   83. Amrish C and Kumar SP: Transdermal delivery of Ketorolac. The Pharmaceutical Society of Japan 2009; 129(3): 373-79.
   84. Vikas S, Seema S, Gurpreet S, Rana AC and Baibhav AJ: Penetration enhancer: a novel strategy or enhancing transdermal drug delivery. International Research Journal of Pharmacy 2011; 2(12): 32-36.
   85. Kalpana B and Lakshmi PK: Transdermal permeation enhancement of Tolterodine Tartrate through invasomes and iontophoresis. Scholars Research Library Journal 2013; 5(6): 119-26.
   86. Regulatory environment for nutraceuticals and functional foods. Valerie Baker Brenda Brady Mary Velin NRC-CISTI National Research Council of Canada 2012; 6
   87. http://www. Inspection. gc. ca/
   88. Malla S, Hobbs EJ and Sogah EK: Functional foods and natural health products regulations in canada and around the world. Nutrition Labels and Health Claims. Report prepared for the Canadian Agricultural Innovation and Regulation Network (CAIRN) 2013.
   89. Hasler MC: Regulation of functional foods and nutraceuticals. A Global Perspective Blackwell Publishing State Avenue Ames Iowa 50014 USA 2007; 37: 89.
   90. http://old.fssai.gov.in/Portals/0/pdf/Direction_Operationalisation_HS_SMP_NF_Nutra_24_11_2016. pdf.
   91. Dillard CJ and German JB: Phytochemicals Nutraceuticals and human health. J Sci Food Agric 2000; 80: 1744-56
       

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       Patel S: Nutraceutical: a review. Int J Pharmacognosy 2020; 7(11): 272-00. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP. 7(11).272-00.

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