Nutritional Cosmetics Formulation II

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) 5

Dosage form advantages  Improve product’s physico-chemical properties  Better delivery system  Accurate dose  Better shelf-life http://www.grammaruntied.com/blog/?p=1233 6

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 7

Formulation considering factors! Bioavailability Stability Technical Feasibility 8

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 http://www.montrealgrandma.com/eyes/ target consumers 10

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) 12

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 13 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 15

NC dosage form: Solid form Advantage:  High stability; appearance and efficacy Convenient in transportation Dosage forms: https://www.bloglovin.com/blogs/elle-sees- 1809672/7-days-to-feeling-good-inside-out • Powder and Granule • Tablet • Effervescent tablet • 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 17

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 18

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 Excipient B 19

Powder  Granule vibrating Granules Segregated powder 20  Powder segregation due to the variation of particle sizes

Granule Pros http://superfoodify.com/9-bee-pollen-benefits-from-fertility-to-weight-loss/  Dust-free and free-flowing  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 21 www.buywholefoodsonline.co.uk/lecithin-granules

Granule http://superfoodify.com/9-bee-pollen • Agglomerated form of powder • Size of 0.2-4 mm (https://www.youtube.com/watch?v=HCP-4P0eoOo) 22 Snow ball rolling down (Graham Li, 2013)

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/ 23 http://www.drygranulationrollercompactor.com/roll-compactor.html

Granule Basic granule preparation; Wet granulation http://pharmatip.blogspot.com/2013/10/wet-granulation-process.html 24

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 25

Granule Granulating agents • Starch (5-25%) • Acacia (1-5%) • Pregelatinized starch (5-10%) • HPMC (2-8%) • MC (1-5%) • PVP (2-8%) 26

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

Pellet http://www.caleva.com/faq/ • Pellets range in size 0.5 mm–1.5 mm • 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/ 28

Pellet Pellet preparation  Spheronization Reddy et al., IJRPLS, 2014, 2(2): 224-235 29

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 30 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 32 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 Compactibility Tensile 33 fraction strength

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 34 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 35

Caplet guess?https://www.dreamstime.com/royalty-free-stock-images- pill-caplet-spilled-container-pills-capletspllied-over-orange- Oval-shape tablet How bEeattseyr tthoanswroaulnlodwtablet ? 36

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) 37

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 38

Plain coating tablet Coating agents • Sugar • Starch • Calcium carbonate • Talc • Titanium dioxide http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1151_viewall.html 39

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 40

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 41

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 42 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 https://www.minimayy.com/2015/01/colgiko-banana-flavour.html 44

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) 45

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 46

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 47

Capsule Type of capsule  Hard Capsules  Soft Capsules 48

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/ 49

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- 50 cherry-fruit-100-vegetarian-capsules-made-in-usa-by-bronson-labs.html