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

Current sales

Potential sales

What is innovation in health?

faster onset of action improved compliance

Why do we need innovation?

Capabilities & Partners

C

B2

B3

B6 B12

B1

E

D3

A

K

Ω-9

Ω-6

Ω-3

CLA

fat soluble

H2O soluble

Poorly absorbed

Stored in the body

Well absorbed

Excreted in urine

MgNa

Bo

KCa

Se

Lutein

Lycopene

Zeaxanthin

Astaxanthin

Betacarotene

Curcumin

Resveratrol

Boswelia

Gingerols

Quercetin

Silymarin

Hesperiden

Rutin

PEA

CoQ10

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

Structure of Micelles

Hydrophilic head = water loving

Lipophilic tail= fat loving

Bile salts act as an emulsifier of lipids

bile salts coat the lipid to form micelles

Pancreatic Lipase - the fat digesting enzyme

Digestive products of lipids

Free Fatty Acids Monoglycerides

Mixed micelles Lipid vesicle

Endogenous

and digested lipidsEndogenous lipids

Inte

sti

nal m

ilie

u

pH

~ 6

.4

Improved absorptionPoor absorption

CoQ10

Higher solubilisationLower solubilisation

SEDDS Aqueous

Media

V. Bala et al., Mol. Pharmaceutics, 2016,13 (10), pp 3518–

3525

for absorption,

the lipids need:

• to adhere

• to be adsorbed

C

B2

B3

B6 B12

B1

E

D3

A

K

Ω-9

Ω-6

Ω-3

CLA

fat soluble

H2O soluble

therapeutic dose

high

lower therapeutic doses

easily absorbed

MgNa

Bo

KCa

Se

Lutein

Lycopene

Zeaxanthin

Astaxanthin

Betacarotene

Curcumin

Resveratrol

Boswelia

Gingerols

Quercetin

Silymarin

Hesperiden

Rutin

PEA

CoQ10

absorption

low

... in any dosage format

CWDsCold Water

Dispersible

Powders using LipiSperse®

CPOsCompressible

Powdered Oils using AquaCelle®

SMEDDsSelf Micro-

Emulsifying

Drug Delivery

Systems using AquaCelle®

AquaCelle®

MICELLAR TECHNOLOGY

LipiSperse®

DISPERSION TECHNOLOGY

®

MICELLAR TECHNOLOGY

• SMEDS for lipophilic compounds

• Stable

• Increased oral bioavailability

• Food effect

• Demonstrated in human studies

®

MICELLAR TECHNOLOGY

0 4 8 12 16 20 240

500

1000

1500

Time (hours)

CoQ

10 C

onc.

(pm

ol/m

l) AquaCelle CoQ10

Commercial CoQ10

Pharmacokinetic StudiesCoQ10n = 45

Pharmacokinetic StudiesFish Oiln = 26

4

4.5

5

5.5

6

6.5

Group 5 AquaCelle 20Group 1 AquaCelle 15Group 4 AquaCelle 10

AUC10h

5

7

9

11

13

15

17

19

Group 5 AquaCelle 20 Group 1 AquaCelle 15 Group 4 AquaCelle 10

AquaCelle Micelles Mean Particle Size

Correlation between micelle size and enhanced bioavailability.

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

CPOsCompressible Powdered oils

Specifically designed for

lipids / oils

Wide variety of active

ingredients

Customisation

AquaCelle®

Compressible Powdered Oils

Overcoming Tabletting Challenges

CPOsCompressible Powdered oils

Potential 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

CPOsCompressible Powdered oils

CWDCold Water Dispersible

Powders using LipiSperse®

Why curcumin? The most researched ingredient!

2018

Google classified turmeric (curcumin)

as the “breakout star” of the

functional food movement of the past

five years.

Curcumin is hot

300% increase in searches Grandview Research

Perfect Dispersion:

Effective Specific Surface Area Large

= ENHANCED BIOAVAILABILITY

Poor Dispersion:

Effective Specific Surface Area Small

= POOR BIOAVAILABILITY

Agglomerate behaving as one single large particlePrimary particle

LipiSperse®

DISPERSION TECHNOLOGY

Agglomerate behaving as one single large particlePrimary particles

Scale is the same (10 microns) in both pictures

LipiSperse®

DISPERSION TECHNOLOGY

With LipiSperse, surface tension is lowered, so water will adhere to particles

Small Contact Angle = Good Wetting

Water

Large Contact Angle = Bad Wetting

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

LipiSperse®

DISPERSION TECHNOLOGY

20 micronsor 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 curcuminoidingestion.

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

0.00

0.20

0.40

0.60

0.80

1.00

1.20

CavaCurmin - Wacker BCM 95 - Arjuna Meriva - IndenaHydroCurc - Pharmako

Plasma levels per mg of curcuminoids ingested (based on published Cmax) (ng/ml)

90% curcumin

10% LipiSperse®

30% curcumin

70% excipient

<20% curcumin

>80% excipient

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