Nanoparticle:
Improvement of Cosmetics Delivery
Systems
Aditya Trias Pradana
Nanoparticles Development in Cosmetics
Microemulsios,
multiple Liposomes and
emulsions and niosomes Solid lipid Nanostructured
solid particle (vesicular nanoparticles lipid carier
(microsponge system)
delivery system)
Compared to liposomes and emulsions, solid paricles possess some advantages
(protection of active compounds against chemical degradation and more flexibility
in modulating the release of the compound)
Excipients of SLN
All excipients used in current topical cosmetic
and dermal pharmaceutical products can be
used
Substances with accepted status can be used
There is no need to use higher surfactant
concentrations compared with marketed
products
Models for Incorporation of Active Compounds
into SLN
Homogeneous
matrix model
Different
models for
the
incorporation
of active
ingredients
Drug- into SLN Drug-
enriched enriched
shell model core model
The structrure obtained is a function of
the formulation composition (lipid, active compound, surfactant) and of
the production conditons (hot vs cold homogenisation
Homogeneous matrix model
A homogeneous matrix with molecularily dispersed
drug or drug being present in amorphous cluster
• When applying the cold homogenisation method
• When incorporating very lipophilic drugs in SLN with the
hot homogenisation method
The bulk lipid
Mechanical breaking by high
contains the
pressure homogenisation leads
dissolved drug in
to nanoparticles having the
molecularily
homogeneous matrix structure
dispersed form,
Drug-enriched shell model
An outer shell enriched with active compound
• When phase separation occurs during the cooling process
from the liquid oil droplet to the formation of a solid lipid
nanoparticle
The compound-
The lipid can The concentration of
enriched shell
precipitate first active compound in
crystallises
forming a the remaining liquid
comparable to the
compound-free lipid increases
eutecticum in the
lipid core continuosly
TX diagram
Drug-enriched core model
Active compound This leads to a
starts membrane
A core enriched
precipipating first controlled release
with active
and the shell will governed by the
compound
have distinctly Fick law of
less drug diffusion
Hot Microemulsion
Emulsion and Solvent Evaporation Method
Solvent Diffusion Method
High Pressure
Homogenization
High Pressure Homogenization
Release of Active Compounds From SLN
Followed by a
prolonged
Initial burst release
release
The release
profiles were
often biphasic
Release of Active Compounds From SLN
Burst release was highest when
producing at highest
temperatures and applying the
hot homogenisation method
High surfactant
concentration leads to
high burst release
Higher the solubility in the water
phase during production, the more
pronounced is the burst effect
Release of Active Compounds From SLN
Heating the lipid/water mixture leads an
increased solubility af the active compound in
the water phase
Cooling leads to supersaturation
of the compound in the water
phase
A solid core has already started
forming leaving only the liquid
outer shell for compound
accumulation
Problems Associated With SLN
Pay-load for a number of drugs too low
Drug explusion during storage
•In higher energy modifications α and β’. During
storage this modifications can transform to the
low energy.
•Due to its high degree of order, the number of
imperfections in the crystal lattice is reduce thus
leading to drug explusion
High water content of SLN dispersions
• The limitation of the lipid concentration was set to 30%, bicoherent
creams were formed in the homogenisation process above 30%.
• The resulting water content 99,9 to 70% can potentially create
problems when incorporating the SLN dispersion into a cream
Concept of Nanostructured Lipid Carriers
Spacially very different lipid molecules
are mixed (blending solid lipids with
liquid lipids/oil)
The resulting matrix of the lipid
particles shows a melting point
depression compared to the original
solid lipid but the matrix is still solid at
body temperature
Basic Idea of NLC
Expulsion of
Giving the
the
lipid matrix a
compound
certain
during storage
nanostructure
is avoided
The pay-load for
active compounds is
increased
Requirements of Excipients
The solubility of active compound in lipid matrices is essential
The oil molecules shouldn’t be participated in the solid
crystalline matrix and the solid cristalline matrix shouldn’t be
dissolved in the liquid lipid
The lipid phase should be more stable to chemical
degradation
The lipid should be degradable and be capable to nanometric
scale
The lipids should have an acceptable toxicological profile
Types of NLC
The
imperfect
The type
amorphous
type
The
multiple
type
Using different molecules “stones”
to build the matrix “wall”
Crystallinity
X-ray difractometer
Differential Scanning
Calorimetry
Nuclear Magnetic Resonance
Particle Size and Morphology
Scanning Electron Microscophy
Particle Size Analyzer
(combined with Zeta Potential analyzer)
In Vitro Occlusion
A beaker of water covered by a
filter paper
The formulation was spread in a
definite amount of 200 mg on a
filter surface of 18,8 cm2
A reference control was a beaker
with a filter only
In Vitro Occlusion
Low F = 100. ((A-B)/A)
melting
lipids Where
F = occlusion factor
A = water loss reference
B = water loss with sample
Highly
crystalline
Highest
particles occlusivity
Smallest
particles
Penetration of Active Compounds Into The Skin
Using the Tesa stripping test
Figure shows the cumulative amount of the
compound in the strips as a function of the strip
number
It is important that the active compounds stay
in the skin,penetrate sufficiently deep but not
to deep leading to systemic availability
Penetration of Active Compounds Into The Skin
Drug Loading / Entrapment Efficiency
Evaluated by ultrafiltration or
centrifugation method
Solution obtained through filtration
Quantify the free drug with HPLC,
spectroscopy or another instriments
In Vivo Test
25 volunteers in which a commercial
cosmeticformulation was applied to the left lower
arm of each volunteer
• Skin hydration was measured as a function of time using
Corneometer CM 825
• Elasticity was quantified with the Cutometer SEM 575
• Wrinkle depth
• Tesa strip was analysed using electron microscopy to detect adhesive
on human skin