This document discusses nutraceuticals, including their definition, examples of functional food components, and regulatory considerations for formulating nutraceuticals and dietary supplements. Some key points: - Nutraceuticals are foods or nutrients that provide health benefits for preventing or treating disease. They include fatty acids, polyphenols, saponins, probiotics, and phytoestrogens. - Formulating nutraceuticals presents challenges due to variations in active ingredients and sensitivities to factors like heat, light, and moisture. Finished products must meet specifications for identity, purity, strength, and stability. - Regulatory requirements for claims substantiation, manufacturing, and product registration vary globally and can

2. Topical Subjects
Nutraceuticals
Formulation of Nutraceuticals and Dietary Supplements
Regulatory Considerations

3. NUTRACEUTICALS
(Let Food be Our Medicine Also)

4. • Greek Physician Hippocrates,
Known as father of Medicine.
(said several centuries ago)
“Let Food be Your Medicine”
The Philosophy behind is:
“Focus on Prevention”

5. • The term “Nutraceutical” was coined from
“Nutrition” & “Pharmaceutical” in 1989 by
Stephen DeFelice,
MD, Founder and Chairman of the Foundation
for Innovation in Medicine (FIM).
• Other words used in the context:
Dietary supplementation, Functional, Multi-
functional Foods, etc.

6. • Nutraceutical can be defined as
“ A food or part of food or nutrient, that
provides health benefits, including the
prevention and treatment of a disease.”

7. Class /
components
Source Potential benefit
1. Fatty acids
CLA
Milk & Meat Improve body
composition,
reduce cancers
n-3 FA(DHA,
EPA)
Fish oils, berseem &
maize
fodder,mustard,linseed,
rapeseed
Reduce CVD &
improve mental,
visual function
EXAMPLES OF FUNCTIONALFOODCOMPONENTS

8. Class /
components
Source Potential benefit
2. Polyphenols
Anthocyanidine Fruits Nutralises free
radicals, reduce
risk of cancer
Catechins Tea,babul pods,mustard
cake,rape seed,salseed
Flavonone Citrus
Flavones Fruits, vegetables,soya
bean
proanthocyanidine Cocoa,
chocolate,tea,rape seed
Reduce CVD
EXAMPLES OF FUNCTIONALCOMPONENTS

9. 3. Saponins Soybeans,GNC,lucer
ne,chick pea
Lower cholesterol,
anti cancer
4.Probiotics / Prebiotics / Synbiotics
Lactobacillus Dahi,yogurt Improve GI health
Fructo -
oligosaccharides
Whole grains,
onions, combination
of Pro & Prebiotics
5.Phytoestrogen
Daidzein ,
Zenistein
Soybean, flax,
lentilseed,maize,
berseem,lucerne,sub
abul fodder
Reduce menopause
symptoms, ↑ bone
health
Lignans Flax,rye, vegetables Reduce cancer and
heart diseases

10. 6.Caroteinoids
β- caroteine
Luteine
Berseem,lucerne ,oat & Nutralises free
maize fodder, Carrots, radicals
vegetabels,fruits
vegetabels Healthy vision
Zeoxanthine Eggs,citrus,corn
Lycopene Tomatoes Reduce prostate
cancer
7.dietary fiber
Insoluble fiber Wheat bran Reduce breast,
colon cancer
β-glucan Oats Reduce CVD
Whole grain Cereal grains

11. Brand name Components Function
Betatene Carotenoids Immune function
Xangold Lutein esters Eye health
Lipoec α-lipoic acid Potent
antioxidant
Generol Phytosterol CHD reduction
Premium
probiotics
probiotics Intestinal
disorder
Soylife Soyabean
phytoestrogen
Bone health
NUTRACEUTICALS AVAILABLE IN MARKET

12. Brand name Components Function
Z-trim Wheat Zero calorie fat
replacer
Linumlife Lignan extract flax Prostate health
Fenulife Fenugreek
galactomannon
Control blood
sugar
Teamax Green tea extract Potent antioxidant
Marinol ω 3 FA, DHA, EPA Heart health
protection
Clarinol CLA Weight loss
ingredient
Cholestaid Saponin Reduce cholesterol
NUTRACEUTICALS AVAILABLE IN MARKET

13. Broadly can be defined as:
•Nutrients: Substances which have established
Nutritional functions e.g. Vitamins, Minerals, Amino
Acids, Fatty acids, etc.
• Herbals/ Phytochemicals: Herbs or Botanical
products
• Dietary Supplements: Probiotics, Prebiotics,
Antioxidents, Enzymes, etc.

14. NUTRIENTS
• Most common Nutrients used/ supplemented
as Nutraceutical are:
Minerals and Vitamins.
or in combination
or in combination with other antioxidants

15. Health Benefits of different common
nutrients
• Vitamins
Fat Soluble Vitamins
• Vitamin A: Acts as antioxidant, essential for growth
and development, maintains healthy vision, skin and
mucous membranes, may aid in the prevention and
treatment of certain cancers and in the treatment of
certain skin disorders.

16. • Vitamin D: Essential for formation of bones and
teeth, helps the body to absorb and use
calcium
• Vitamin E: Antioxidant, helps to form blood
cells, boosts immune system
• Vitamin K: Essential for blood clotting

17. Water Soluble Vitamins
• Vitamin C: Antioxidant, necessary for healthy
bones, gums, teeth and skin. Helps in wound
healing, prevent from common cold
• Vitamin B 1: Helps in carbohydrate metabolism,
essential for neurological function.
• Vitamin B 2: Energy metabolism, maintain
healthy eye, skin and nerve function.

18. • Vitamin B 3: Energy metabolism, brain function
• Vitamin B 6: Helps to produce essential
proteins, convert proteins to energy
• Vitamin B 12: Help in producing genetic
material, formation of RBC, maintenance of
CNS, synthesis of amino acids, involved in
metabolism of protein, fat and carbohydrate.

19. • Folic acid: Helps in RBC formation, formation of
genetic material of cell, very much essential
during pregnancy
• Pantothenic acid: Aids in synthesis of
cholesterol, steroids, and fatty acids, crucial for
intraneuronal synthesis of acetylcholine

20. Vitamins like Compounds
• L- Carnitine: Helps in oxidation of fatty acids, role in
oxidative phosphorylation,
• Choline: Lipotropic agent, used to treat fatty liver and
disturbed fat metabolism,
• Inositol: For amino acid transport and movement of
Potassium and sodium,
• Taurine: Helps in retinal photoreceptor activity, bile
acid conjugation, WBC antioxidant activity, CNS
neuromodulation, platelet aggregation, cardiac
contractibility, sperm motility, insuline activity,

21. • Minerals:
• Calcium: essential for bone and teeth, maintaining
bone strength, nerve, muscle and glandular function,
blood clotting,
• Iron: energy production, Hb, oxygen transport,
• Magnesium: for healthy nerve and muscle function,
bone formation,
• Phosphorous: energy production, phosphorylation
process, bone and teeth, for genetic material,

22. • Cobalt: component of Vit. B 12 and B 12
coenzymes,
• Copper: Hb and collagen production, function of
heart, energy production, absorption of Iron,
• Iodine: proper function of Thyroid gland,
• Chromium: with insulin it helps in conversion of
carbohydrate and fat into energy, treatment of
diabetes,

23. • Selenium: Antioxidant, functioning of heart
muscle, part of GPX enzyme,
• Zinc: Essential for cell reproduction, for
development in Neonates, wound healing,
production of sperm and testosterone
hormone,

24. • Herbals:
• Aloe vera: Anti-inflammatory, emollient, wound
healing,
• Evening Primrose oil: Dietary supplement of
linoleic acid, treatment of atopic eczema,
• Garlic: Antibacterial, antifungal, antithrombotic,
antiinflammatory,
• Ginger: carminative, antiemetic, treatment of
dizziness

25. • Ginseng: Adaptogen,
• Green tea: Antioxidant, reduces risk of CVD,
enhances humoral and cell mediated Immunity,
• Vegetables, fruits, whole grain, herbs, nuts and
various seeds contain an abundance of
phenolic compounds, terpenoids, sulphur
compounds, pigments etc. that has been
associated with protection / treatment of certain
disease conditions,

26. •Phytochemicals:
• Phytochemicals could provide health benefits
as:
1. Substrate for biochemical reactions
2. Cofactors of enzymatic reactions
3. Inhibitors of enzymatic reactions
4. Absorbents that bind to & eliminate undesirable
constituent in the intestine
5. Scavengers of reactive or toxic chemicals

27. 6. Enhance the absorption and / or stability of
essential nutrients
7. Selective growth factor for beneficial bacteria
8. Fermentation substrate for beneficial bacteria
9. Selective inhibitors of deleterious intestinal
bacteria

28. Various Phytochemicals
Phytochemicals Source Role
Tocotrienols &
tocopherols
Grains Suppressed the growth of
diverse tumors cell lines via
initiation of apoptosis and
concomitant arrest of cells in
the G1 phase of the cell cycle
Carotenoids Fruits &
vegetables
Antioxidants, protects against
uterine, prostate, colorectal,
lung and digestive tract
cancers, and protection to
other antioxidants.

29. Limonoids Citrus fruits Inhibiting phase I
enzymes & inducing
phase II detoxification
enzymes in liver, provide
protection to lung tissue.
Phytosterols Various
plants
Exhibit anti-inflammatory,
anti-neoplastic, anti-
pyretic & immune-
modulating activity,
decrease cholesterol
Phenolic
constituents
Various
plants,
wholegrain
Antioxidants, lowers the
risk of CHD, diabetes,
hypertension etc.

30. Flavonoids Grapes, wines Action against free
radicals, free radicals
mediated cellular
signaling, inflammation,
allergies, platelet
aggregation, &
hepatotoxins
Catechin &
gallic acids
Grapes,
berries, cocoa,
green tea,
acacia spp.
Antioxidants, free
radical scavenging
ability, inhibition of
eicosanoid synthesis,
reduces CHD
Isoflavonoids Soybeans Treating cancers &
osteoporosis

31. Anthocyanidins Fruits & flowers Antioxidants & anti-
mutagenic properties
Glucosinolates Cruciferous Activators of liver
detoxification
enzymes, inhibit the
neoplastic effect of
various carcinogens
Indoles Reduces estrogen-
dependent cancer
risk,
Fiber Various
vegetables,
fruits,
Protects against
colorectal diseases,

32. Method to enhance active
components in food
• Manipulating the diet to get maximum
level of active components
• Combination of food ingredients rich in
nutraceuticals
• Fortifying food with active ingredients
• By fermentation of food products
• Changing food habits to natural type of
diet

33. CONCLUSION
• Nutraceuticals are present in most of the food
ingredients with varying concentration
• Concentration, time and duration of supply of
nutraceuticals influence human health
• Manipulating the foods, the concentration of
active ingredients can be increased
• Diet rich in nutraceuticals along with regular
exercise, stress reduction and maintenance of
healthy body weight will maximise health and
reduce disease risk

34. Formulation of
Nutraceuticals and
Dietary Supplements:
Formulation and Regulatory
Challenges
Pharmaceutics and Novel Drug Delivery
Systems Conference 2016

35. NUTRACEUTICAL
nu·tra·ceu·ti·cal also nu·tri·ceu·ti·cal
Nutraceuticals are gaining attention due to the
increasing consumer market share for wellness
products
noun ˌnü-trə-ˈsü-ti-kəl : a specially treated food,
vitamin, mineral, herb, dietary supplement etc., that you
eat or drink in order to improve your health
Full Definition of NUTRACEUTICAL
A foodstuff (as a fortified food or dietary supplement)
that provides health benefits in addition to its basic
nutritional value
http://www.merriam-webster.com/

36. Introduction
• Solid dosage formulation and process design for
drug products and nutrition products is similar.
• Purpose and regulatory requirements may differ
• Desire for a safe and effective dosage form is
the same
• Desire for most cost effective formulation and
process is the same

37. Formulation Challenges of Nutrition
Tablet Design
• Botanicals are complex with multiple chemical
components
• Can contain up to 50 active ingredients; 70- 90%
of the formula can be actives
• Botanicals and extracts can vary based on
region the crop was grown, season grown in and
other factors
• Generally large dose per daily serving

38. Formulation Challenges of Nutrition
Tablet Design
• Significant variation in active ingredient particle
size, compression and flow characteristics within
one dosage form
• Large variation in heat, light and moisture
sensitivity of ingredients within one formula
• Requires addition of overages

39. Formulation Challenges of Nutrition
Tablet Design
Hardness, Friability
Uniformity
Test method
Disintegration, Dissolution
Stability

40. STABILITY FACTORS
Solid State Stability
Degradation Forces
pH stability
Moisture Activity
Microbial bio burden
ANALYTICAL FACTORS
Chemical Analysis
Impurities/Contaminati
on
Structural Analysis
SEM Images
X-ray Diffraction
Thermo analysis (DSC/
TGA)
NMR
FTIR
TECHNOLOGICAL
FACTORS
Particle
size/Micronization
Surface area
Porosity
Crystal structure
Powder flowability
Compressibility
Plastic/brittle
fracture
Moisture content
As we move toward stricter regulations and
higher quality standards….
Optimized
Choice
Formulation Challenges of Nutrition Tablet Design

41. Formulation Challenges of Nutrition
Tablet Design
Finished good specifications for:
• Identity
• Purity
• Strength
• Composition
• Shelf Life
cGMP for manufacturing, storage and
handling, packaging and labeling

42. Claims Substantiation
• Different countries have different
requirements
• Established generic claims for vitamins
and minerals
• Due to regulations or USPs, may compel
companies to conduct clinical research
Challenges:
Choice of study population
Nature of nutraceuticals

43. Regulatory Considerations
The Regulatory Landscape has a
strong influence …

44. Global Formulation and Process
Design
Just a Few References That Must be Considered
• WHO
• British
Pharmacopoeia
• US Pharmacopoeia
• European
Pharmacopoeia
• China
Pharmacopoeia
• China GB National
standards
• Japan
Pharmacopoeia
• Codex Alimentarius
• ICH
• Korea HFF Codex
• Japan Positive list for
use in foods (not a
drug ingredient)

45. Registration Certifications May Be
required
an
d
Certification requirements often apply to excipients
as well as active ingredients
• GMO Free
• Halal
• Kosher
• WADA Compliance
– (World Anti Doping Agency) country
product specific

46. More Challenges for Global
Formulation
• Registration category/classification
– According to claims and 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

47. (Powders,
Nutrition – Food Products
Drinks and Bars)
Notification or No Registration
Market
Registration Market (low/med
complexity )
Registration Market (med/high
complexity )

48. Nutrition - Categories Excluding Food
Products
(Health Supplements, TCM’s, Health Foods and items
considered “Drugs/Medicines”)
Notification or No Registration
Market
Registration Market (low/med
complexity )
Registration Market (med/high
complexity )

49. Nutrition Classifications (not
comprehensive)
• Dietary Supplement
• Food
• NHP- Compendial
• NHP- Non Compendial
• Health Functional Food
• Tablet Food
• Health Food
• General food
• Drug
• Traditional Chinese Medicine •
• OTC
• Food Supplement
• Traditional Medicine
• Complimentary
Medicine
• Functional Food
• Novel Food
• Phytotherapeutic
• Food complement
• Natural product
• Natural Products,
Drug
• Herbals
Nutrient Supplement
• Food for Specified
Health Uses

50. Allowance of Ingredients Reference:

51. Several Countries have their own testing
requirements or “positive list” that impact
choices
• Do not always reciprocate the USP
standards for excipients
– China- CHP, MOH, GB Guobiao, or “National
Standard”
– Korea, HFF (Health Function Food Code)
and MFDS (Ministry of Food and Drug Safety)
re-org March 2013
– Japan, JFHA- Japan Health Food Association
(positive list for food additives)

52. Example: Malaysia
• Four nutrition categories- Functional
Foods, Traditional Medicine, OTC, Health
Supplement.
• Many Products fall into the Food Drug
Interface (FDI)
• Depending on characteristics and
ingredients, they may be regulated by the
National Pharmaceutical Control Bureau
(NPCB) or the Food Safety and Quality
Division (FSQD) of the Ministry of Health

53. National Pharmaceutical Control Bureau
First Edition, January 2013 , MOH
Malaysia

54. Towards Global Harmonization
International Alliance of Dietary/
Food Supplements Associations
Global Information, Science and Regulation
– IADSA is the leading international expert association
regarding the globalization of food supplement
markets and increasing regulatory challenges.
– Includes food supplement associations from 6
continents
– IADSA aims to build an international platform for
debate and a sound legislative and political
environment for the development of the food
supplement sector worldwide.

55. ASEAN (Association of Southeast
Asian Nations)
10 Member States
Approx 520 million
population

56. Regulatory trends: Global
Formulation
(Nutrition)
• Regulatory scrutiny is increasing, but with
regional differences
• Increased focus on substantiation of health
claims through clinical studies
• Food safety issues will result in more restrictions
• Some regions heading towards globally
harmonized rules (EU, ASEAN)
• *However, regulatory harmonization delayed in
some regions due to local interests

57. At Amway Nutrilite
We Nurture Our
Ingredients
Every Step of
the Way

58. • A Library of more than 2,500 Botanicals
• Bioassays for 6 mains functions: Antioxidant, DNA Health,
Energy Health, Anti-Inflammation, Glycation and
Pigmentation

59. FTL to Product Development
Technologies to support Discovery and
Development
• Agricultural Research
• Chemistry & Bioassay (Analytical
Sciences Lab)
• Clinical Testing
• Process Technology
• Quality
• Rapid Prototyping

60. Nutrilite is the world's number one
selling vitamins and dietary supplements
brand

61. Summary
–Formulation of Nutraceuticals is similar and yet
different than pharmaceutical formulation
–Regulations vary by different countries – there is
a need for harmonization
–Formulation, testing and labeling of nutraceuticals
is getting stricter as we enhance safety and
quality
–Nutrilite at Amway will continue to make
advancements in formulation for optimal health
and wellness

62. ASEAN HARMONIZATION OF
TMHS (Traditional Medicine Health Supplement)
REGULATIONS

63. ASEAN Proposal: Global List of
Restricted
Additives & Excipients
• Currently many countries and regions
maintain “positive lists”
• ASEAN Guiding principles for entry of
additives and excipients into ASEAN List
of Restricted Additives and Excipients
– Development stage
– Not listed in CODEX or any international
reference

64. Any Questions or Additions

66. Reference:
1.Clinical Skills for Pharmacists, A Patient-Focused Approach, 3rd Ed, ISBN 978-0-323-
05485-0, by Karen J Tetze, 2012
2.Clinical Pharmacy & Therapeutics, 5th Ed, ISBN – 978-0-7020-4294-2, by Roger
Walker & Cate Whittlesea, 2012
3.Clinical Anatomy and Physiology of the visual Views, 3rd Ed, ISBN: 978-1-4377-1926-
0, by Butterworth-Heinemann, 2012.
4.Clinical Guidelines : Diagnosis and Treatment Manual, 7th Ed, ISBN: 2-906498-69-6,
By L.Blok (MD) et al.
5.Clinical Pharmacology, 9th Ed, ISBN 0443064814, by P.N. Bennett and M.J. Brown,
2003

67. Study Questions
Define the following generic terms of pharmacy:
[Nutraceutical, Nutrient, herbal, vitamin, phytochemical, Hardness, Friability Uniformity, Disintegration, Dissolution
Stability, purity, strength, composition shelf life, Clinical Pharmacy, Oedema, Hypothyroidism, Dosage, Medication,
Compliance, Pharmaceutical Care, Apothecary, Pharmaceutical compounding, Ayurvedic Pharmacy, Antiquity
Pharmacy, Middle Ages Pharmacy, Modern Pharmacy, Retail pharmacy, Alchemy, Remedy, Drug, Medicine, Cure, Care,
Trephining, Millennium, Symptoms, Renaissance, Disease, Illness, Microbes, Civilization, Herbal remedies, Usage, Side
effects, Quantities, Dosages, Storage, Pharmacopeia, Pharmacology, Pharmaceutics, Pharmacokinetics, Therapeutics,
Pathophysiology, Evolution, Patient counseling, Nutrition, Antibiotics, Chemotherapy, Pain management, Semiotician,
Physician, Pharmacist, Diagnosis, Mutual respect, Honesty/ Authenticity, Open Communication, Cooperation,
Collaboration, Empathy, Sensitivity, Promotion, Competence, Assurance, Confidence, etc]
Respond to the following questions:
In line with historical background of originality of pharmacy, How was disease thought of in early civilization and
how was it treated.
What are some of the contributions to the practice of pharmacy from around the world regions such as Asia,
Greece, Roman Empire, Arabia, Europe.
Why has there been a trend toward fewer independent pharmacies in some world pharmaceutical established
operations as compared to those of national institutes
Historically, how has the role of the pharmacist evolved overtime to its present time nature
Write on the ways the modern-day pharmacist has impacted patients’ health and safety
State and explain the critical role of clinical pharmacy in a designed health sector
Describe in details what is considered when demographic data is compiled
State and explain the essential considerations in patient medication process
Explain in details the process of Pharmaceutical care and it role and stages in the provision of patient care
State and explain the critical components of patient counselling during medication process and how it can
effectively be provided.

68. Group work discussional questions for Journal Club
Meetings:
State and explain the critical role of clinical pharmacy in a designed health
sector
Describe in details what is considered when demographic data is compiled
State and explain the essential considerations in patient medication process
Explain in details the process of Pharmaceutical care and it role and stages in
the provision of patient care
State and explain the critical components of patient counselling during
medication process and how it can effectively be provided.
Categorize the types of nutraceuticals in terms of components, source and
potential benefits
State and describe health benefits of human body according to each type food
nutrients that is eaten as food
What are requirements for formulation of nutraceuticals and food
supplements for their respective medicinal values