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