Delivery systems for nutraceuticals Enhanced bioavailability and improved functionality for lipophilic nutrients

Delivery systems for nutraceuticals Enhanced bioavailability and improved functionality for lipophilic nutrients

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What is innovation in health? faster onset of action improved compliance

Why do we need innovation?

Capabilities & Partners

D 3 A K E Ω-3 Ω-6 Ω-9 CLA fat soluble Resveratrol Curcumin Boswelia Poorly absorbed Stored in the body Lycopene Betacarotene PEA Silymarin Gingerols Lutein Zeaxanthin Astaxanthin CoQ 10 Hesperiden Quercetin Rutin B 1 C B 3 B 2 B 6 B 12 Na Mg K Ca Se Bo H 2 O soluble Well absorbed Excreted in urine

Lipid: a fat-like molecule that does not have the ability to dissolve in water

Digestion and solubilization of dietary oils: Bile salts and Pancreatic lipase Christopher J. H. Porter et al. Nature Reviews Drug Discovery, Vol. 6, March 2007, 231-248

Bile salts act as an emulsifier of lipids Emulsify = break large fat droplets into small droplets

Bile salts act as an emulsifier of lipids Structure of Micelles Hydrophilic head = water loving Lipophilic tail = fat loving bile salts coat the lipid to form micelles

Pancreatic Lipase - the fat digesting enzyme Digestive products of lipids Free Fatty Acids Monoglycerides

Intestinal milieu ph ~ 6.4 for absorption, the lipids need: to adhere to be adsorbed SEDDS CoQ 10 Endogenous lipids Mixed micelles Lipid vesicle Aqueous Media Endogenous and digested lipids Lower solubilisation Higher solubilisation V. Bala et al., Mol. Pharmaceutics, 2016, 13 (10), pp 3518 3525 Poor absorption Improved absorption

D 3 A E Ω-3 K Ω-6 Ω-9 CLA Lycopene Betacarotene Zeaxanthin Lutein Astaxanthin PEA CoQ 10 fat soluble Resveratrol Curcumin Boswelia Gingerols Silymarin Quercetin Rutin Hesperiden therapeutic dose high absorption low B 1 C B 3 B 2 B 6 B 12 Na Mg K Ca Se Bo H 2 O soluble lower therapeutic doses easily absorbed

... in any dosage format

AquaCelle MICELLAR TECHNOLOGY LipiSperse DISPERSION TECHNOLOGY SMEDDs Self Micro- Emulsifying Drug Delivery Systems using AquaCelle CPOs Compressible Powdered Oils using AquaCelle CWDs Cold Water Dispersible Powders using LipiSperse

MICELLAR TECHNOLOGY

SMEDS for lipophilic compounds Stable Increased oral bioavailability Food effect Demonstrated in human studies

MICELLAR TECHNOLOGY

CoQ 10 Conc. (pmol/ml) 1500 AquaCelle CoQ 10 1000 Commercial CoQ 10 500 0 0 4 8 12 16 20 24 Time (hours)

Pharmacokinetic Studies CoQ 10 n = 45

Pharmacokinetic Studies Fish Oil n = 26

Correlation between micelle size and enhanced bioavailability. AUC10h 19 AquaCelle Micelles Mean Particle Size 6.5 17 6 15 5.5 13 11 5 9 4.5 7 4 Group 5 AquaCelle 20Group 1 AquaCelle 15Group 4 AquaCelle 10 5 Group 5 AquaCelle 20 Group 1 AquaCelle 15 Group 4 AquaCelle 10

AquaCelle not only increases bioavailability it also removes fishy reflux. Regular fish oil, from oil or Powder, floats on top of stomach contents AquaCelle micelles disperse in the aqueous environment of the gut

CPOs Compressible Powdered oils

AquaCelle Compressible Powdered Oils Specifically designed for lipids / oils Wide variety of active ingredients Customisation

CPOs Compressible Powdered oils Overcoming Tabletting Challenges

CPOs Compressible Powdered Potential oils CPO Applications Enable a broad range of potential applications: tablets hard capsules beverages foods protein shakes infant formula meal replacements Fish oils Algal oil Krill oil Chia oil CLA EPO Lavender oil

CWD Cold Water Dispersible Powders using LipiSperse

Why curcumin? The most researched ingredient! 2018

Curcumin is hot Google classified turmeric (curcumin) as the breakout star of the functional food movement of the past five years. 300% increase in searches Grandview Research

LipiSperse DISPERSION TECHNOLOGY Primary particle Agglomerate behaving as one single large particle Perfect Dispersion: Effective Specific Surface Area Large = ENHANCED BIOAVAILABILITY Poor Dispersion: Effective Specific Surface Area Small = POOR BIOAVAILABILITY

LipiSperse DISPERSION TECHNOLOGY Primary particles Agglomerate behaving as one single large particle Scale is the same (10 microns) in both pictures

LipiSperse DISPERSION TECHNOLOGY Water Small Contact Angle = Good Wetting Large Contact Angle = Bad Wetting With LipiSperse, surface tension is lowered, so water will adhere to particles Water + + Goal is to allow water to engulf the lipophilic crystal + + + + + + + + + +

LipiSperse DISPERSION TECHNOLOGY Repulsive forces between the particles prevent agglomeration or aggregation: allowing CWD Powders to have proper particle dispersion

20 microns or 20 thou of mm

... in any dosage format

Pharmacokinetic Study 18 healthy male and female volunteers Single dose Randomised Double blinded study Crossover - Seven volunteers Plasma concentrations were determined at baseline and at regular intervals over a 24-hour period following curcuminoid ingestion.

Cmax 807 Tmax 1 hr Total AUC 1898 ng/ml P <0.05

Plasma levels per mg of curcuminoids ingested (based on published Cmax) (ng/ml) 1.20 1.00 0.80 0.60 0.40 0.20 0.00 CavaCurmin - Wacker BCM 95 - Arjuna Meriva - IndenaHydroCurc - Pharmako

10% LipiSperse 90% curcumin >80% excipient <20% curcumin 70% excipient 30% curcumin

enquiries@pharmako.com.au Bronwen.Kerr@ingredients-plus.com philip@ingredients-plus.com