Nutritional Cosmetics

Formulation

www.coresupplementtech.com

Sarita Sangthong, Ph. D.

1
 The preformulation of NC product

Active ingredient (s)

NC product dosage form

2
 The formulation of NC product

Active ingredient (s)

NC product dosage form

with the

maximum efficacy
3
 Formulation considering factors!

1. Physico-chemical properties of active ingredients

2. Dosage form

3. Excipients

4. Formulation process

5. Preservation

6. Stability https://lifehacker.com/treat-failure-like-a-scientist

7. Appearance

4
Dosage form
Definition :
• A term for the physical characteristics of a product
which contains the active substance and almost invariably
other ingredients, such as excipient, fillers, flavours,
emulsifiers, preservatives (Segen's Medical Dictionary, 2012)

• The administration form of the completed product

(World Health Organization, 2014)

• A dosage form is the physical form in which an active

ingredient is produced and dispensed, such as a tablet,
a capsule (U.S. Food and Drug Administration, 2012)

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Dosage form advantages

 Improve product’s physico-chemical properties

 Better delivery system

 Accurate dose

 Better shelf-life

http://www.grammaruntied.com/blog/?p=1233

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Dosage form advantages

 Improve product’s physical appearance

 Consumer’s attractiveness

 Consumer’s organoleptic sensory;

taste, sight, smell, touch

 Consumer’s perception;

healthy, beauty, ease of use

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Formulation considering factors!

Bioavailability Stability

Technical Feasibility

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 Types of oral administration dosage form

• Solid • Semi-solid • Liquid

https://www.linkedin.com/pulse/defying-nature-
rejuvenating-skin-from-inside-out-beauty-sampathi/

http://www.medicdrugstore.com/index.php https://www.ebay.com/sch/Meiji-Vitamins-Dietary- 9
?route=product/product&product_id=124 Supplements/180959/bn_25283718/i.html?_fsrp=1&
Dosage form design; Concerns

 Characteristics of the active ingredient(s)

− Physical appearance
− Recommended usage dose
− Physicochemical property
− Pharmacodynamic property
− Pharmacokinetic property
− Compatibility to the excipient
https://ods.od.nih.gov/factsheets/VitaminE-Consumer/

 Concept of NC product to
target consumers http://www.montrealgrandma.com/eyes/

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Dosage Form Compositions

nutriliving.com/shop/superfood-superboost ninesights.ninesigma.com/

Active ingredients + Excipients

alibaba.com/product-detail/GMP-TGA-certified-Krill-Oil-Softgel http://www.istockphoto.com/ 11
Excipients

Definitions;

• A substance with no pharmacological action,

used as a drug diluent or vehicle
(Illustrated Dictionary of Podiatry and Foot Science by Jean Mooney, 2009 Elsevier Limited.)

• Any inert substance used to bulk up or dilute a

drug, or as a vehicle for a drug.
(Collins Dictionary of Medicine, Robert M. Youngson 2004, 2005)

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 Excipients
 Tablet
1. Diluents or fillers: increase the bulk of the formulation

2. Binder: cause the adhesion of powdered active

ingredients and excipients

3. Lubricants: assist the smooth tableting process

4. Disintegrating agents: promote tablet breakup after

administration

5. Coating: improve stability, control disintegration, or to

enhance appearance
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Modified from Allen (2008 )Clinical Therapeutics (30) 2102-2111
 Excipients
 Solution
1. Solvent: dissolve the active substances and others

2. Flavors and sweeteners: make the product more

palatable

3. Colorants: enhance product appeal

4. Preservative: prevent the microbial growth

5. Stabilizers (eg, antioxidant, chelating agent): prevent

active substances decomposition

Modified from Allen (2008 )Clinical Therapeutics (30) 2102-2111 14

Dosage form design;
Solid form

https://sciencing.com/convert-between-iu-mg-mcg-8298314.html

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NC dosage form: Solid form

Advantage:
 High stability; appearance and efficacy
Convenient in transportation

Dosage forms:
• Powder and Granule
• Tablet
• Effervescent tablet https://www.bloglovin.com/blogs/elle-sees-
1809672/7-days-to-feeling-good-inside-out
• Chewable tablet
• Gummy
• Capsule

http://keepingbee.org/granulated-honey/

https://www.prevention.com/eatclean/collagen-supplements 16
 Powder
Most of the materials (>90%)–both active ingredients
and excipients–are provided in the powder form
Pros
 Easy to adjust the dose in the formulation process

 Easy for administering; drinks or foods

 Suitable for high dose-required active ingredients

 Pleasant flavor, smell, and color can be improved

Cons
 Not suitable for strong unpleasant smell ingredient

 Not suitable for highly hydroscopic ingredients

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 Powder
Natural origin
prevention.com/eatclean/collagen-supplements

• Animal products: lactose

• Plant products: microcrystalline cellulose, starch,

pregelatinized starch

Semi-synthetic origin
• Sodium starch glycolate, Hydroxypropyl cellulose

Synthetic origin
• Pyrrolidone, polyvinyl pyrrolidone (PVP), magnesium
stearate
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 Powder
Basic powders preparing technique
• Trituration: mortar and pestle (small scale)

• Geometric dilution: mixing the same amount of two

ingredients at a time

Active Excipient A Excipient A

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Excipient B
 Powder  Granule

vibrating

Granules

Segregated powder
 Powder segregation due to the variation of particle sizes 20
Granule
Pros
 Dust-free and free-flowing http://superfoodify.com/9-bee-pollen-benefits-from-fertility-to-weight-loss/

 Suitable for high dose-required active ingredients

 Good solubility

 Attractive appearance

Cons
 Not suitable for thermal and moisture sensitive
active ingredients (wet granulation)
 Not benefit for masking of strong unpleasant
taste of active ingredients
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www.buywholefoodsonline.co.uk/lecithin-granules
Granule

• Agglomerated form of powder http://superfoodify.com/9-bee-pollen

• Size of 0.2-4 mm

(https://www.youtube.com/watch?v=HCP-4P0eoOo)
Snow ball rolling down (Graham Li, 2013)
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Granule
Basic granule preparation; Dry granulation

 Suitable for high dose active ingredient

 Heat and moisture sensitive active ingredient

 Powder produced along the process

nutriliving.com/shop/superfood

ninesights.ninesigma.com/

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http://www.drygranulationrollercompactor.com/roll-compactor.html
Granule
Basic granule preparation; Wet granulation

http://pharmatip.blogspot.com/2013/10/wet-granulation-process.html

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 Granule
Basic granule preparation; Wet granulation

Binder solution containing binder/suspension/gelatinized binder

Ethanol:  Better for moisture sensitive products
Dry more quickly
 Higher in cost and cost of disposing
Aqueous (water):
Cheaper
Safer and easier to handle and dispose
Adversely affect stability by hydrolyzing some ingredient
Longer drying times and longer exposure to heat and abrasion
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Granule

Granulating agents
• Starch (5-25%)

• Acacia (1-5%)

• Pregelatinized starch (5-10%)

• HPMC (2-8%)

• MC (1-5%)

• PVP (2-8%)

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 Pellet

• The aggregation of fine powders or granules

• Small, free-flowing, spherical units
• Mostly available as a coated pellet with polymer film in
order to obtain a controlled release effect

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http://www.samedanltd.com/magazine/15/issue/152/article/2935
 Pellet

• Pellets range in size 0.5 mm–1.5 mm

http://www.caleva.com/faq/

• Can be compressed into tablets

• Can be filled into hard gelatin capsules

http://www.gea.com/en/stories/mups-production.jsp http://www.procysbi.com/hcp/about-procysbi/
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Pellet

Pellet preparation  Spheronization

Reddy et al., IJRPLS, 2014, 2(2): 224-235

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 Tablet

• The powders, granules, and/or http://secureswitch.com/?wekhq=1830546118

pellets of active ingredient is combined

with excipients are compressed into a hard tablet

• There are various shapes, sizes and colors

Powder  Granules  Pellet  Tablet

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http://www.empr.com/medical-news/tablet-splitting-when-is-it-ok/article/391470/ http://www.gea.com/en/stories/mups-production.jsp
Tablet
• Tablets are available in fast acting, slow release,
controlled release, enteric coated, film coated,
sublingual, chewable and other formulations

https://pharmatreasures.blogspot.com/2012/02/what-is-difference-between-dissolution.html 31
Tablet; compression process

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Gamlen , 2015. Tablet Press, Scientific papers
 Tablet; evaluations
• Tabletability is the relationship between
compaction pressure and tensile fracture stress.
• Compressibility is the relationship between
compaction pressure and solid fraction.
• Compactibility is the relationship between
tensile fractures stress and solid fraction.
Compaction
pressure

Solid Tensile
fraction Compactibility strength 33
 Tablet
 Excipients
1. Diluents or fillers: increase the bulk of the formulation

2. Binder: cause the adhesion of powdered active ingredients

and excipients

3. Lubricants or glidants: assist the smooth tableting process

4. Disintegrating agents: promote tablet breakup after

administration

5. Coating: improve stability, control disintegration, or to

enhance appearance

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Modified from Allen (2008 )Clinical Therapeutics (30) 2102-2111
Tablet

Component Content

Active 300 mg

Filler (lactose powder) 182.5 mg

Disintegrant (3% croscarmellose) 15 mg

Lubricant (0.5% magnesium stearate) 2.5 mg

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Caplet

guess? https://www.dreamstime.com/royalty-free-stock-images-
pill-caplet-spilled-container-pills-capletspllied-over-orange-

Oval-shape tablet

Easy to swallow
How better than round tablet ?

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Coated tablet

Advantages:
• Hiding the unfavorable smell or taste

• Enhance the tablet's appearance

• Make the tablet smoother and easier to swallow

• Control the release rate of the active ingredient

• Make it more resistant to the environment

(extending its shelf life)

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Coated tablet

Feature Sugar coating Film coating

Appearance Rounded, glossy Original shape, semi-matte

Weight increasing 30-50% 2-3%

Break-line Inapplicable Applicable

Process Multi-steps Single step

Coating time > 8 hrs. 1.5-2 hrs

Example
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Plain coating tablet

Coating agents

• Sugar

• Starch

• Calcium carbonate

• Talc

• Titanium dioxide

http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1151_viewall.html
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Films coating tablet

Coating agents:
• Hydroxypropyl methylcellulose

• Methylcellulose

• Hydroxypropylcellulose

• Carboxymethylcellulose sodium

• Mixture of cellulose acetate phthalate and

polyethylene glycol

http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1151_viewall.html

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Coated tablet

Feature Sugar coating Film coating

Appearance Rounded, glossy Original shape, semi-matte

Weight increasing 30-50% 2-3%

Break-line Inapplicable Applicable

Process Multi-steps Single step

Coating time > 8 hrs. 1.5-2 hrs

Example
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Enteric coated tablet

• Tablet which are designed to release the drug in the

intestine
• They resist degradation in the acidic pH in stomach
and stay intact
• Once they reach basic pH in intestine, they release
their contents https://www.studyread.com/types-of-capsules

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Pharmacology: Oral Meds Absorption, GABAY MEDICAL library (2008)
Enteric coated tablet

Coating agents

Polymers Dissolution pH

Shellac (esters of aleurtic acid) 7.0

Cellulose acetate phthalate (CAP) 6.2

Poly(methacrylic acid-co-methyl methacrylate) 5.5 - 7.0

Cellulose acetate trimellitate (CAT) 5.0

Poly(vinyl acetate phthalate) (PVAP) 5.0

Hydroxypropyl methylcellulose phthalate 4.5 - 5.5

(HPMCP) https://www.studyread.com/types-of-capsules 43
Chewable Tablet

• Smooth disintegrated by chewing

• Highly contained sweeteners; mannitol,
sucrose, lactose, sorbitol, inositol
• Easy to consumed

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https://www.minimayy.com/2015/01/colgiko-banana-flavour.html
 Effervescent Tablet

• Effervescent products are based on

a chemical incompatibility between

the acidic and the basic sources!

• An autocatalytic reaction in the presence

of water which produces a gaseous product.

RCOOH + NaHCO3 → RCOONa + H2O + CO2

(Organic acid) (Alkaline metal) (Salt) (Carbon dioxide)

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Effervescent Tablet TRY: Define the function
of ingredients

Vitamin C Effervescent Tablet (1.5 grams) http://formulation.vinensia.com/

Ingredient Mass (mg) % (w/w) Function

1. Vitamin C 500 33.33 Active ingredient

2. Pyroxidine 20 1.33 Active ingredient

3. PVP 45 3.06 Binder

4. Sucrose 225 15 Filler

5. Citric acid monohydrate 208 13.86 Acid source

6. Tartaric acid 222.9 14.86 Acid source

7. Sodium bicarbonate 249.5 16.63 Base source

8. PEG 8000 30 2 Lubricant

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Effervescent Tablet

 Pleasant taste and smell

 Easy to be consumed (as a drink)

 Increase in absorption due to the tight junction of

cell membrane is widen by CO2

 Not suitable for moisture sensitive

compounds

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Capsule

Type of capsule

 Hard Capsules

 Soft Capsules

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 Hard Capsule

• Cylindrical shape
• Available in different standards sizes
• Two pieces with short cap and large body
• Mostly filled with dry contents; powder, granules, tablet
• Filling is done after manufacturing the capsule

http://www.saintytec.com/types-sizes-capsule-use-fully-automatic-capsule-filling-machine-updated-guide/
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Hard Capsule

 Hard gelatin capsule - animal-derived

 Hard hypromellose* capsule - plant-derived

*(HPMC, Hydroxypropyl)methyl cellulose)

https://www.vitaoto.com/tart-cherry-vitacherry-hiactives-whole-tart-
cherry-fruit-100-vegetarian-capsules-made-in-usa-by-bronson-labs.html 50
Study of Consumer Preferences:
Solid Oral Dosage Forms

Capsugel (2009)
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Liquid Filled Hard Capsule

• New technology https://s3.amazonaws.com/cpsl-web/kc/pdfs/library/

Liquid-Filled_Hard_Capsule_Technology_2016.pdf

 Fast released two-become-one capsule

 Thin shell without plasticizer or preservative
 High protection for oxygen and heat sensitive
active ingredients
 Suitable for low-melting point and high viscosity
fillings

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 Soft Capsule

• More elastically shell due to

plasticizers such as glycerin or polyhydric alcohol (e.g., sorbitol)

• Exist in different shapes such oval, tube, etc.

• A single piece that is always sealed

• Holds liquids, semi liquids and unstable substances

• Filling and sealing takes place in a combined operation

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Enteric Coated Capsules

• Capsule coated for targeting intestine

absorption
• See “ Enteric coating ”
• Same target as Enteric tablet
• Better in >>> EasyGuess!
to swallow

https://www.studyread.com/types-of-capsules 54
Gummy and gummy stick

Advantage
 Attractive
 Pleasant flavor
 Easy to consume
 Heat sensitive compounds
Compositions
• Water
• Active ingredients
• Gelatin
• Sweeteners and flavors
• Colorants

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Gummy and gummy stick

Process
Melting  Molding  Cooling  Polishing or Coating

https://www.albanesecandy.com/

http://www.scarymommy.com/wine-gummy-bears-recipe/

https://cbdfx.com/products/cbd-hemp-gummy-bears-300mg
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Dosage form design;
Semi-solid Form

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NC dosage form: Semi-solid form

Advantage:
Attractive
Convenient in consumption
Pleasant taste

Dosage Form:
• Jelly

Compositions
• Gelatin
• Sugar
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Dosage form design;
Liquid form

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NC dosage form: Liquid form

Ready to drink
 Commonly pleasant flavor
 Not suitable for sensitive molecule
 High cost of transportation

Dosage form:
• Aqueous drink http://www.laneige.com/hk/en/product/collagen

• Concentrated
• Syrup

https://ashieda.com/products/best-anti-aging- 60
collagen-beauty-drink-fast-results-10-day-supply
NC dosage form: Liquid form

• Solutions: The NC is dissolved completely into a liquid

form. Products are on-shelve as a ready to drink form.

• Suspensions: The NC is mixed with, but not completely

dissolved into a liquid. It needs to be shaken before
administration. Less popular than solution.

http://www.sappe.com/en/ http://www.sappe.com/en/ 61
Formulation and Process Development

• Blending, drying, granulation, coating and capsule

development for solid dosage form

• Mixing development for liquid dosage form

• Dosage form specification development

• Excipient compatibility and ration determination

• Formulation of products- the right order of mixing

• Formulation optimization for up-scale production

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Formulation Evaluation Define which
dosage form need
to be evaluated by
• Compressibility evaluation each evaluation

• Content uniformity evaluation

• Disintegration testing

• Dissolution testing

• Friability testing

• in-vitro bioequivalence determination

• Powder flow determination

• Stability assessment

• Tap-density testing
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http://pharmapproach.com/pilot-plant-scale-up-techniques/

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Which dosage form  produces a gaseous
product in the presence of water?

Effervescent
??????

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