Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March...
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Delivery systems for nutraceuticals Enhanced bioavailability and improved functionality for lipophilic nutrients
Transcript of Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March...
Delivery systems for nutraceuticals Enhanced bioavailability and improved functionality for lipophilic nutrients
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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
