rainer h. müller nanopearls · rainer h. müller no. 2 content • short look into cosmetic...
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PharmaSol GmbH No. 1AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 1
Lipid Nanoparticles for Improved Formulationof
Cosmetic and Pharmaceutical Actives
Rainer H. Mü[email protected]
NLC®
Nanopearls®
PharmaSol GmbH No. 2AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 2
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 3AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 3
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 4AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 4
Let us go back in cosmetic history………….
1968 Invention of liposomes by Bingham(liposome size in nanometer range, i.e. liposomes were nanotechnology)
1986 Introduction of first cosmetic product to market:
Capture® by Dior
…..to learn from history for future innovative products
PharmaSol GmbH No. 5AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 5
PharmaSol GmbH No. 6AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 6
Extraordinary market success:
Most people did not know what a liposome is
but
they bought the product when the name liposome was on thepackaging!
Association: Association: liposomeliposome = = qualityquality
PharmaSol GmbH No. 7AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 7
Dermal history since the liposomes
• many attempts to develop a similar successful system
• examples: nanoemulsions
microemulsions
multiple emulsions
MDS - microsponge delivery systems
transfersomes (by Cevc / Munich, Germany)
PharmaSol GmbH No. 8AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 8
2005The novel approach in cosmetics & pharma:
NLC = Nanostructured Lipid Carriers
PharmaSol GmbH No. 9AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 9
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 10AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 10
Development of lipid nanoparticle concept
Polymericnanoparticles
polymer(solid)
liquid lipid(=oil)
o/w emulsion
solid lipid
SLN / Lipospheres1st generation
solid lipidblend
NLC2nd generation
surfactant/ stabilizer layer
Traditional Carriers Lipid Nanoparticles
PharmaSol GmbH No. 11AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 11
Definitions• Lipid Nanoparticles in solid state:
derived from o/w emulsions, simply replacing the liquid lipid (= oil) by a solid lipid (i.e. solid at body temp.)
• SLN – Solid Lipid Nanoparticlesproduced from solid lipids
• NLC – Nanostructured Lipid Carriers:produced from blend of solid and liquid lipids, but particles are in solid state at body temperature
PharmaSol GmbH No. 12AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 12
FeaturesLipid nanoparticles with solid matrixMean particle diameter: 80 - 1000nmProduction by dispersion techniques, e.g. high pressurehomogenizationLoading* with active compounds, e.g.
1-2% prednicarbate, prednisolone, cyclosporine etc…10% Benzophenone-3, Allure6% Retinol (Vitamin A)
24% Tocopherol (Vitamin E)(* calculated as %age of solid lipid matrix)
PharmaSol GmbH No. 13AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 13
NLC Technology / Nanopearls®
novel particulate carrier for pharmaceutical / cosmetic products
Nanoparticles based on regulatory accepted excipients, physiological / natural solid lipids (renewable resources)
Application examples: protection of chemically labile active compounds &controlled release (CR) - because of solid matrixpenetration enhancement of activesdermal CR (e.g. drugs, perfumes, repellents)oral absorption enhancement
PharmaSol GmbH No. 14AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 14
NLC the more intelligent system
SLN: tendency to form perfect crystals active expulsione.g. tristearin
NLC: inhibit crystallization process by mixing “spatially” very different molecules imperfections in lattice
mixture solid &liquid lipids
PharmaSol GmbH No. 15AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 15
Nanostructure of NLC
imperfection (“holes” in lattice)
The particle matrix of NLC is composed of spatially very different molecules whichcannot form a perfect lipid crystal
PharmaSol GmbH No. 16AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 16
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 17AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 17
The Production Technology
Basic principles:
high pressure homogenization
• equipment can be qualified & validated
• accepted by regulatory authorities in production lines used for pharmaceutical parenterals
• existing industrial production lines for cosmetics / i.v. pharmaceutical parenteral emulsions can be used
PharmaSol GmbH No. 18AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 18
Production Technology - Basics
basic mixture:solid lipidliquid lipidemulsifier(co-emulsifier)water
(SLN: solid lipids, 0.1% - 30% solid)
solid content> 30%
PharmaSol GmbH No. 19AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 19
Production by high pressure homogenization
Melt lipid (>40°C) and dissolve active compound
Disperse active-containing lipid melt in hot surfactantsolution = pre-emulsion
Homogenize pre-emulsion at >40oC, 250 bar, 2 cycles = nano-emulsion
cooling, solidification
NLC / Nanopearls®
PharmaSol GmbH No. 20AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 20
“old” SLN vs. novel NLC
PharmaSol GmbH No. 21AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 21
Gaulin 5.5 - 150 kg/h
PharmaSol GmbH No. 22AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 22
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 23AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 23
Oral application example: cyclosporine annual sales: appr. 1.2 billion US $ “old” Sandimmun: problem of variation in
bioavailability “new” Sandimmun: high plasma peak (microemulsion) (> 1000 ng/ml) target of previously developed SLN: combine advantage of “old” & “new” Sandimmun, i.e.
no plasma peak and low variation in bioavailability
PharmaSol GmbH No. 24AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 24
Oral delivery: cyclosporine study
animal: pigs (n=3)
application: via gastric catheter
comparison: SLN dispersion vs. Sandimmun® Neoralcyclosporine particles
PharmaSol GmbH No. 25AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 25
Oral cyclosporine - blood profiles
0
400
800
1200
1600
2000
0 2 4 6 8 10 12 14 16 18 20 22 24tim e [h]
cycl
ospo
rine
con
c. [n
g/m
l] cyclosporine SLNSandimmun Neoral
PharmaSol GmbH No. 26AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 26
Oral drug delivery with lipid nanoparticles
What are the mechanisms?
What are the advantages?
PharmaSol GmbH No. 27AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 27
Mechanisms of oral lipid nanoparticles
general adhesiveness of very fine particles (nanoparticles)
adhesion processes very reproducible (= little variation in bioavailability)
lipids known to support absorption of a number of drugs* (Trojan horse)
* W. N. Charman, Proc. of 26 th Int. Symp. of CRS, Boston 1999
PharmaSol GmbH No. 28AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 28
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 29AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 29
Technical advantages of NLC vs. liposomesProblems of liposomes:1. physical stability in o/w systems
2. quantitative analysis difficult
3. chemical stability of labile actives
Advantages of NLC:1. high physical stability due to solid state of particle matrix
2. physical stability easy to prove (DSC)
3. chemical stabilisation of actives due to solid character
PharmaSol GmbH No. 30AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 30
Physical stability: DSC analysis• Determine melting enthalpy of solid lipid matrix of
Nanopearls®
this allows– to prove molecular loss of lipid particles during
incorporation in cosmetic product
– to prove 100% presence of intact, undissolvedNanopearls® during shelf live of product(„standard“ stability in cosmetics: 3 months)
PharmaSol GmbH No. 31AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 31
Chemical stability of incorporated activesNanoemulsions and Liposomes:Limited protection of actives because:• lipophilic actives are in exchange with water due to fluidcharacter of oil droplet / liposome bilayer
• hydrophilic actives in liposome core diffuse through bilayer inouter water phase
NLC:Enhanced protection of actives:• solid state minimizes exchange of actives withwater phase (diffusional law by Einstein)
PharmaSol GmbH No. 32AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 32
Chemical stability of incorporated actives
Nanoemulsion Nanoparticle dispersion
e.g. polymericnanoparticle or NLC
modified after Rolf Petersen, Berlin
PharmaSol GmbH No. 33AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 33
Chemical stabilisation effect of NLCStability of Retinol
in Nanopearls® dispersion(Compritol ATO 888 10% stabilized with Miranol C32) versus Miglyol emulsion (10% oil,1.5% Tween 80).
Reference: V. Jenning, Ph.Dthesis, 1999, Free Univ. of Berlin
020406080
100
cont
ent[
%]
RT
020
406080
100
0 20 40 60 80 100 120 140 160 180time [days]
cont
ent[
%] 40°C
N
N
E
E
PharmaSol GmbH No. 34AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 34
Film formation on skin - principle mechanism
Interparticle space:= identical (24 %)
however: different hydrodynamics
nanoparticle pores: capillary condensationeffect (similar to dryingagent silica gel!)
H2O evaporation
small"capillary pores"
skin
200 nm
Top view:
large pores
tightly packedlayer of lipid-nanoparticles
Occlusion effectlarge lipidmicroparticles
2 µm
PharmaSol GmbH No. 35AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 35
How work NLC in cosmetic creams and lotions?
NLCOil dropletsCream
water
Skin
PharmaSol GmbH No. 36AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 36
Situation on damaged skin
damaged areas of lipid film
Lipid film on skin thin film
Skin
Reduced protection, moisture loss, distorted cell function
PharmaSol GmbH No. 37AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 37
Action of NLC in creams
Repair !Re-inforce !
Skin
NLC film
PharmaSol GmbH No. 38AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 38
Occlusion effect - in vitro test1. Filter paper on beaker with water2. Apply formulation onto filter3. Measure amount of water evaporated4. Reference: beaker with filter only5. Calculate occlusion factor F: 0 = evaporation from ref.
100 = no evaporation at allfilter
formulationH2O H2O
REFH20 H20
Literature: method after de Vringer, 1992; company: Yamanouchi
PharmaSol GmbH No. 39AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 39
Occlusion factor of a commercial o/w cream (left) and a cream withincorporated Nanopearls® (right) as a function of time. (Dingler et al., J. Microencapsulation, 1999)
Occlusion effectCream vs. Cream with Nanopearls®
0
10
20
30
40
50
60
cream cream + Nanopearls
6 hours24 hours48 hours
Occ
lusi
onfa
ctor
PharmaSol GmbH No. 40AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 40
Penetration of:
coenzyme Q10 and Tocopherolinto the stratum corneum(SC) from aqueous
Nanopearls® dispersionvs. solid lipid microparticlesdispersion
Increased penetration of actives
(cumulative amount of skin strips 2-9; skin strip 1 = non-penetrated fraction).
0
10
20
30
40
50
60
70
80
90
fractionpenetratedin SC
fractionpenetratedin SC
microparticlenanoparticle
Tocopherol coenzyme Q 10
Con
tent
activ
e[1
0 %
]
PharmaSol GmbH No. 41AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 41
Principle mechanisms of UV protection
• Particular sunscreen:UV
• Molecular sunscreen: heat, light
synergistic effect: sunscreen in NLC
PharmaSol GmbH No. 42AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 42
Release of molecular sunscreen and side effects
0
2
4
6
8
10
0 5 10 15 20 25
time [h]
Rel
ease
[%]
Nanopearls Emulsion
Release of benzophenone-3 from emulsion is twice as high as fromNanopearls® dispersion*
* Wissing, Ph.D. thesis, Free University of Berlin, 2001
PharmaSol GmbH No. 43AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 43
Performance & Effects on skin
• adhesiveness to skin• film formation, repair of stratum corneum• occlusion effect• skin hydration ↑• wrinkle depth ↓• increased / modulated penetration of actives• UV protection system
⇒ i.e. skin healing, caring & protective effects!
PharmaSol GmbH No. 44AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 44
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance• Access to NLC products• Summary
PharmaSol GmbH No. 45AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 45
Lipid Nanoparticles in the German Pharmaceutical Press
Lipid Nanoparticles
Smart delivery systemfor dermal actives
Application to the skin is the keyto release the actives
PharmaSol GmbH No. 46AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 46
Nanopearls® in cosmetic products• Lotions• Creams & Gels• Decorative cosmetics• Sprays
• Mode of incorporation
Blend NLC concentrate with existing product / newformulation
PharmaSol GmbH No. 47AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 47
Present state of commercialisation
• 1st non-exclusive license sold for cosmetic finalproducts in 2005 to:
Dr. Rimpler GmbH
• 1st product launch announced at the PCIE in Paris2005
• presentation of first 2 NLC products on the world at thecosmetic trade fair „Beauty“ in Munich, autumn 2005
PharmaSol GmbH No. 48AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 48
PharmaSol GmbH No. 49AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 49
Composition of NLC coenzyme Q10 suspension
Coenzym Q10 4.8 %
Cetylpalmitat
Miglyol 812
surfactant
Water up to 100.0 %
PharmaSol GmbH No. 50AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 50
In vivo penetration of Q10: NLC vs. references
0
5
10
15
20
25
1 2 3 4 & 5 6 & 7 8 & 9
Tape number
Cum
ulat
ive
%ag
e Q
10
NLCEmulsionParaffinum liquidum
PharmaSol GmbH No. 51AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 51
Measurement of skin hydration: Corneometer
• Not invasive method• Measuring time: 1 sec• Principle: capacity
changes• Capacity changes are
dependent upon the watercontent in stratumcorneum (ε = 78 at 32 oC)
MPA5 with Corneometer 825(Courage and Khazaka, Köln)
Nanopearls®
PharmaSol GmbH No. 52AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 52
Q10 skin hydration in vivo: NLC vs. NLC-free
no NLCw ith NLC
0
5
10
15
20
25
30
Can
ges
[%]
Long-term study, 42 days,measurement 12 h after last application
PharmaSol GmbH No. 53AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 53
Examples of available loaded NLC• Coenzyme Q10
• Vitamin E
• Tocotrienol
• Retinol
• Black current oil (BCO)
• KuKui oil
• use of special lipids: e.g. Carnauba wax
also service forcustomer tailor-made
NLC available
PharmaSol GmbH No. 54AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 54
South Korean
Top Model no. 1
for the introduction of the
NLC Supervital products
in the pretigous line
IOPE1. Sept. 2006
PharmaSol GmbH No. 55AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 55
Cosmetic products in the series by Amore Pacific: SuperVital cream (left), SuperVital serum (middle) and SuperVital eye cream (right).
PharmaSol GmbH No. 56AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 56
PharmaSol GmbH No. 57AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 57
PharmaSol GmbH No. 58AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 58
PharmaSol GmbH No. 59AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 59
Product name Producer/ distibuter
Market introduction
main active ingredients
Cutanova Cream Nano Repair Q10Intensive Serum NanoRepair Q10Cutanova Cream NanoVital Q10
Dr. Rimpler/ Germany
10/200510/200506/2005
Q 10, polypeptide, Hibiscusextract, ginger extract, ketosugarQ 10, polypeptide, mafane extractQ 10, TiO2, polypeptide, ursolicacid, oleanolic acid, sunflowerseed extract
SURMER Crème Legère Nano-ProtectionSURMER Crème Riche Nano-RestructuranteSURMER Elixir du Beauté Nano-VitalisantSURMER Masque Crème Nano-Hydratant
Isabelle Lancray/ France
11/2006 kukuinut oil, Monoi Tiare Tahiti®, pseudopeptide, milk extract from coconut, wild indigo, noni extractkukuinut oil, Monoi Tiare Tahiti®, pseudopeptide, milk extract from coconut, wild indigo, noni extractkukuinut oil, Monoi Tiare Tahiti®, pseudopeptide, milk extract from coconut, wild indigo, noni extractkukuinut oil, Monoi Tiare Tahiti®, pseudopeptide, milk extract from coconut, wild indigo, noni extract
Reference: Euro Cosmetics 2007
PharmaSol GmbH No. 60AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 60
SuperVital- Cream- Serum- Eye cream(line: IOPE)
Amore Pacific/South Korea
09/2006 coenzyme Q10, ω-3 and ω-6 unsaturated fatty acids
NLC Deep Effect Eye SerumNLC Deep Effect Repair CreamNLC deep effect reconstruction serum
BeateJohnen/ GermanyHSE 24
12/200605/2007
coenzyme Q10, highly active oligo saccharidesQ10, TiO2, highly active oligosaccharidesQ10, actyl hexapeptide-8, highly active oligo saccharides
Regenerationscreme Intensiv
Scholl/ Germany
03/2007 urea, avocado oil, macadamia nuts oil
Reference: Euro Cosmetics 2007
PharmaSol GmbH No. 61AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 61
Content• Short look into cosmetic history• Definitions & special features• Production process & large scale production lines• Pharma / nutritional supplements: oral bioavailibility
enhancement• Pharma & Cosmetic: Performance on skin• Cosmetics: products on the market & performance
• Access to NLC products• Summary
PharmaSol GmbH No. 62AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 62
Finished Cosmetic Products• PharmaSol owns world wide IP rights for finished
cosmetic products [email protected]
• Purchase license on a product-by-products base
• Produce own NLC suspensions or source out production of:
- NLC concentrate or- complete production of NLC productto cooperation partner of PharmaSol
PharmaSol GmbH No. 63AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 63
Dr. Rimpler GmbH – partner of PharmaSolfor introducing NLC-technology
Dr.Rimpler GmbHNeue Wiesen 10
D-30900 Wedemark
Founded 1986 by Prof. Dr. Manfred Rimpler
Health & Care development, production
Cosmetic-GMP & approved by §13 AMG
Company Profile54 employees
Production capacity 2500 kg per shift
www.Rimpler.de
PharmaSol GmbH No. 64AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 64
Service by Dr. Rimpler GmbH
• Development of customized NLC in cooperation with PharmaSol
• Contract manufacturing of NLC concentrate for licensees of PharmaSol (finished products)
• Production of bulk product (creams, lotions etc. with NLC)
• Ready-made products incl. packaging
• Cosmetic testing via external partners
PharmaSol GmbH No. 65AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 65
Production machines
Unimix LM 3
First step for scaling up from laboratory
Unimix SRM 250
Batch from 60 to 250 kg
Unimix SRC 1000
Batch from 250 to 1000 kg
PharmaSol GmbH No. 66AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 66
Filling equipment
Jar - Fillpack
60 jars/min
Tube - Norden 400
2 machines with 40 tubes/min
Bottle - Fillpack
120 bottles/min
Airless - Valois
10 bottles/min
PharmaSol GmbH No. 67AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 67
Summary Pharmaceuticals• NLC can be made with regulatory accepted
excipients
• NLC are produced with production technology already available in pharmaceutical industry
• Make-ability of technology proven by cosmetics products on the market
• primary delivery routes:- dermal application- oral administration (poorly soluble drugs)
PharmaSol GmbH No. 68AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 68
Summary Cosmetics• unloaded NLC have own skin effects
• loaded NLC increase- chemical stability & - “bioactivity” of actives
• NLC can easily be incorporated in creams, lotion etc
• physical stability high, easy to prove quantitatively
• extremely short time form invention to market(6 years)
• Products: about 20 in about 1.5 years
PharmaSol GmbH No. 69AmsterdamFree University Technology Presentation 2007Rainer H. MüllerNo. 69
NLC Product Examples