Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March...
Transcript of Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March...
![Page 1: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/1.jpg)
Delivery systems for nutraceuticals Enhanced bioavailability and improved functionality for lipophilic nutrients
![Page 2: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/2.jpg)
Current sales
Potential sales
![Page 3: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/3.jpg)
What is innovation in health?
faster onset of action improved compliance
![Page 4: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/4.jpg)
Why do we need innovation?
![Page 5: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/5.jpg)
Capabilities & Partners
![Page 6: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/6.jpg)
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
![Page 7: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/7.jpg)
Lipid: a fat-like molecule that does not have the ability to dissolve in water
![Page 8: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/8.jpg)
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
![Page 9: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/9.jpg)
Bile salts act as an emulsifier of lipids
Emulsify = break large fat droplets into small droplets
![Page 10: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/10.jpg)
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
![Page 11: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/11.jpg)
Pancreatic Lipase - the fat digesting enzyme
Digestive products of lipids
Free Fatty Acids Monoglycerides
![Page 12: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/12.jpg)
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
![Page 13: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/13.jpg)
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
![Page 14: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/14.jpg)
... in any dosage format
![Page 15: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/15.jpg)
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
![Page 16: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/16.jpg)
![Page 17: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/17.jpg)
®
MICELLAR TECHNOLOGY
![Page 18: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/18.jpg)
• SMEDS for lipophilic compounds
• Stable
• Increased oral bioavailability
• Food effect
• Demonstrated in human studies
![Page 19: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/19.jpg)
®
MICELLAR TECHNOLOGY
![Page 20: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/20.jpg)
0 4 8 12 16 20 240
500
1000
1500
Time (hours)
CoQ
10 C
onc.
(pm
ol/m
l) AquaCelle CoQ10
Commercial CoQ10
![Page 21: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/21.jpg)
Pharmacokinetic StudiesCoQ10n = 45
![Page 22: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/22.jpg)
Pharmacokinetic StudiesFish Oiln = 26
![Page 23: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/23.jpg)
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.
![Page 24: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/24.jpg)
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
![Page 25: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/25.jpg)
CPOsCompressible Powdered oils
![Page 26: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/26.jpg)
Specifically designed for
lipids / oils
Wide variety of active
ingredients
Customisation
AquaCelle®
Compressible Powdered Oils
![Page 27: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/27.jpg)
![Page 28: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/28.jpg)
Overcoming Tabletting Challenges
CPOsCompressible Powdered oils
![Page 29: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/29.jpg)
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
![Page 30: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/30.jpg)
CWDCold Water Dispersible
Powders using LipiSperse®
![Page 31: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/31.jpg)
![Page 32: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/32.jpg)
Why curcumin? The most researched ingredient!
2018
![Page 33: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/33.jpg)
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
![Page 34: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/34.jpg)
![Page 35: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/35.jpg)
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
![Page 36: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/36.jpg)
Agglomerate behaving as one single large particlePrimary particles
Scale is the same (10 microns) in both pictures
LipiSperse®
DISPERSION TECHNOLOGY
![Page 37: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/37.jpg)
![Page 38: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/38.jpg)
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
![Page 39: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/39.jpg)
Repulsive forces between the particles prevent agglomeration or aggregation: allowing CWD Powders to have proper particle dispersion
LipiSperse®
DISPERSION TECHNOLOGY
![Page 40: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/40.jpg)
20 micronsor 20 thou of mm
![Page 41: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/41.jpg)
![Page 42: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/42.jpg)
... in any dosage format
![Page 43: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/43.jpg)
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.
![Page 44: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/44.jpg)
• Cmax 807• Tmax 1 hr• Total AUC 1898 ng/ml• P <0.05
![Page 45: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/45.jpg)
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)
![Page 46: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/46.jpg)
90% curcumin
10% LipiSperse®
30% curcumin
70% excipient
<20% curcumin
>80% excipient
![Page 47: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/47.jpg)
![Page 48: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/48.jpg)
![Page 49: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/49.jpg)
![Page 50: Delivery systems for nutraceuticals Enhanced ... · Nature Reviews | Drug Discovery, Vol. 6, March 2007, 231-248. Bile salts act as an emulsifier of lipids Emulsify = break large](https://reader036.fdocument.pub/reader036/viewer/2022062601/5e513067ac41de60a80feff2/html5/thumbnails/50.jpg)