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FORMULATION

PLAMEN KIRILOV1*, ANH KHANH LE CONG1, ALICE DENIS1, HALIMA RABEHI1,


SILVIA RUM2, CARLA VILLA2, MAREK HAFTEK1,3, FABRICE PIROT1,4
* Corresponding author
1. Université 1, EA 4169 "Aspects fondamentaux, cliniques et thérapeutiques de la fonction cutanée",
SFR Lyon-Est Santé – INSERM US 7 – CNRS UMS 3453
Laboratoire de Pharmacie Galénique Industrielle, ISPB, 8 Avenue Rockefeller, 69737 Lyon, Cédex 08, France
2. DIFAR - Dipartimento di Farmacia dell'Università,
Sezione di Chimica del Farmaco e del Prodotto Cosmetico VIale Benedetto XV 3, 16132 Genova, Italy
3. Université Claude Bernard Lyon 1, EA 4169 "Aspects fondamentaux, cliniques et thérapeutiques de la
fonction cutanée", SFR Lyon-Est Santé – INSERM US 7 – CNRS UMS 3453 Plamen Kirilov
Laboratoire de Dermatologie, ISPB, 8 Avenue Rockefeller, F-69737 Lyon, Cédex 08, France
4. Groupement Hospitalier Eduard Herriot – Service Pharmaceutique –
Fabrication et contrôles des médicaments, Pavillon X, Place d’Arsenal, 69437 Lyon, Cédex 03, France

Organogels for cosmetic


and dermo-cosmetic applications
Classification, preparation and characterization of
organogel formulations - PART 2*

KEYWORDS: organogel, organogelator, LMOG, formulation, cosmetic product, dermo-cosmetic application

Abstract Organogels are semi-solid systems in which an organic liquid phase is immobilized by a three-dimensional
network composed of low molecular weight or polymeric components. Recently, they have raised an
increasing interest in the pharmaceutical, cosmetic and food industry. Numerous cosmetic products based on organogels
formulations are marketed. Many studies now focus on new applications of organogels and therefore, aim to develop novel systems
of organogels and new generations of organogelators.
In this review, methods of preparation and characterization of organogel will be described, as well as different classifications and
current applications in the cosmetic field, more particularly in dermo-cosmetics.

PREPARATION OF ORGANOGEL bonds between polar molecules and phosphate groups of


the lecithin molecules. A further addition of a small amount
Generally, organogels are prepared by heating a mixture of water results in the formation of long, flexible and worm-
of a gelator and an organic liquid (or organic solvent) in like tubular micellar structures. Tubular micro-structures, thus
order to obtain a dispersion mixture, which after cooling at formed, overlap and entangle with each other to form a
room temperature, leads to the formation of a jelly structure. three-dimensional gel network of fibrils and fibers, which
Organogelator molecule interactions induce a gelator possesses viscoelasticity and thermo-reversibility properties.
organization into well-defined aggregates, such as tubular The organic liquids get entrapped in the spaces between the
rods, fibrils and fibers. Mainly three methods are used for the entangled reverse micelles (35) (Figure 3).
organogel preparation: fluid-filled fiber mechanism, solid
fiber mechanism and mechanical homogenization and Solid fiber mechanism
microirradiation method. The solid fiber mechanism involves the dispersion of the solid
organogelator into the apolar solvent by hot emulsification
Fluid-filled fiber mechanism and formation of an apolar liquid mixture of organogelator.
The gelation process takes place with the addition of a After cooling to room temperature, organogelator molecules
trace amount of water into the solution of apolar solvent precipitate out as fibrils which undergo non-covalent
and surfactant, such as lecithin molecules. Before the physical interactions amongst each other and form a three-
addition of water, the surfactant is dispersed in the organic dimensional fibrillar network structure. The apolar solvent
medium. With the addition of small amount of water, the is then immobilized by the gelator fibers and a semi-solid
surfactant molecules assemble themselves together to form organogel is thus formed (30, 36, 37) (Figure 4).
micelles. Further addition of water makes the short tubular
or cylindrical micellar aggregate. The water molecules bind Mechanical homogenization and microirradiation
stoichiometrically to the hydrophilic head of the surfactant This novel technique consists in a high speed
molecules. The water molecules link two surfactant molecules homogenization using Ultra-Turrax® before microwave
together which forms linear networks with the hydrogen heating. Commonly, organogels are formed using

16 H&PC Today - Household and Personal Care Today, vol. 10(4) July/August 2015
technique might be of great advantages,
especially in industrial scale when reduction
in the preparation time and low energy
consumption are always appreciated (38).

CHARACTERIZATION OF ORGANOGELS

Evaluation and physicochemical


characterization are very important steps
after organogel formation. Organogels
show particular physico-chemical properties
listed as follow and which permit their
characterization (Table 1) (6-9, 30).
Figure 3. Schematic representation of the fluid-filled fiber organogelator organization (35).

Various characterization parameters are


used to confirm the purity and the stability of
prepared organogels. In Table 2 are reported
various characterization parameters and
different techniques which are used for their
evaluation (6, 20, 30, 36).

ORGANOGELS FORMULATIONS USED


FOR COSMETIC AND DERMO-COSMETIC
APPLICATIONS

Organogel nanoparticle dispersions as


immobilization systems for a sunscreen agents
LMOGs are frequently used in cosmetology for
their desirable physical organization properties
Figure 4. Solid fiber mechanism. Transmission electron microscopy (TEM) and SEM within the oil phase and their capacity to
micrographs of orhanogelator solid fiber self-assembling (30, 36, 37).
jellify the organic solvents in small quantities.
Novel particles obtained from a LMOG and
an organic liquid present many advantages:
they show a better encapsulation rate of
lipophilic or amphiphilic molecules, with a
homogeneous repartition into the particles
(21, 22). The active ingredient, as a liquid,
can be directly jellified and be the main
constituent of the formulation; the consistency
can easily be controlled depending on
the organogelator wt%. The surface of
nanoparticles can be functionalized by a
stabilizing agent (polymer or surfactant) for a
better vectorization (Figure 5).

Based on gelled nanoparticle concept,


sunscreen semi-solid dispersions have been
Figure 5. Preparation concept of gelled nanoparticle dispersion (21, 22).
prepared and their physico-chemical
properties studied. Gelled particle dispersions
of sunscreen organic mixture – butyl-
conventional heating which has been mentioned earlier. metoxydibenzoyl-methane (Avobenzone®, UVA solar filter,
However, nowadays, microwave irradiation is more and powder) dissolved in 2-ethylhexyl-2-3,3-diphenylacrylate
more used as an alternative heat source in laboratories (Octocrylene®, UVB solar filter, viscous liquid) and HSA were
instead of conventional heating. The main advantage of obtained by hot emulsification (T > Tgel), with a polymer (PVA
microwave irradiation is the rapidity of heating the products. 80) as a stabilizing agent, and cooling at room temperature
Indeed, heating a system for 30 min is time and energy (T < Tgel). The dispersion observation by TEM showed
consuming. Therefore, microwave heating appears to be spherical particles with a mean diameter of 600 nm, a size in
an economic alternative method for producing organogels. accordance with DLS measurements (Figure 6).
Microwave-assisted heating has several advantages like
high efficiency, low energy consumption and homogeneity. These results confirmed that the sunscreen particle size was in
Microwave heating is then a hopeful method to obtain agreement with the necessity to keep the particles on the skin
organogels with suitable characteristics. This novel surface, avoiding their penetration through the epidermis.

H&PC Today - Household and Personal Care Today, vol. 10(4) July/August 2015 17
The UV spectroscopy
observations showed more
important absorption of the
gelled particles comparing
to that of corresponding
emulsion droplets. A
rheological investigation
allowed to determine the
Tgel, thus confirmed their
gelled state. This last point
was also proved by zeta
potential measurements.
A comparative aging
study of the emulsion and
corresponding dispersion
showed greatly enhanced
stability after gelation (36, 37).
The preparation and
physico-chemical
evaluation of a stable
dispersion in water of
organogel nanoparticles
containing a sunscreen
molecule (EHMAB) (39,
40) was also realized.
Particles were obtained
by hot emulsification
in the presence of a
stabilizing agent (PVA 80).
HSA has been chosen as
organogelator and almond
oil as the oily phase.
Nanoparticle diameter is
Table 1. Physico-chemical properties and specific characteristics of organogels.
found to be between 100
and 5000 nm (Figure 7).

According to the HSA


gelation test results, EHMAB
was mixed with almond
to favor the gelation
phenomenon and thus
lower the minimum gelation
concentration (MGC) of
HSA. The Tgel and Tmelt
determination by rheology
permeated to predict the gel
phase transition according
to the gelator concentration.
Concerning the gelled
particles, stable dispersions
were obtained by ultrasound
emulsification method. An
investigation of the influence
of different dispersion
ingredients (oil, gelator
and stabilizer) showed the
importance of the HSA and
the stabilizing agent(s) for the
size, polydispersity index (PI)
and zeta-potential values of
nanoparticles and the stability
of their dispersions. Thanks to
Table 2. Characterization parameters and evaluation techniques of organogels. the preliminary formulation
tests, stable EHMAB

18 H&PC Today - Household and Personal Care Today, vol. 10(4) July/August 2015
formulations with HSA, cosmetic
oil, antiperspirant actives, and
sometimes a copolymer (42).
Even when used at relatively low
concentration, HSA tends to give
rise to rigid gels that have limited
capacity to retain fluids. It has
been found that HSA organogels
modified by incorporating selected
copolymers produce a more
stable crystalline structure, which
improves the oil retention, and thus
Figure 6. Chemical structure of gelled sunscreen particle ingredients. Gelled a better fracture resistance. Better
sunscreen particle preparation concept and corresponding TEM micrographs rheological properties also assess
(36, 37).
a facilitated spreadability over the
skin (28, 29, 39). Moreover, modified
HSA organogels allow to overcome
the use of higher hydrophilic
lipophilic balance (HLB) surfactants,
in particular anionic, many of which
are potentially harsher on skin
than the more lipophilic lower HLB
surfactants.

Organogels in make-up products


In care and make up products, it is
Figure 7. TEM and SEM micrographs of sunscreen gelled nanoparticles and macroscopic common to find a structured, namely
structure of their dispersion (concentrated and diluted samples) (39, 40). gelled or rigidified, liquid fatty phase.
This is particularly the case in solid
compositions such as balms and
nanoparticles, with mean size of 450 nm and zeta-potential value lipsticks, eye shadows, concealers and foundation. This
above - 30 mV, were obtained. A comparative aging study of structuring is generally obtained with the aid of waxes or
the nanoparticle dispersion showed a greatly enhanced stability fillers. Unfortunately, these adjuvants tend to mattify the
after gelation. Finally, the gelation process is thus a functional composition which is not always wanted for some products.
technique to improve both the photoprotective ability and It is necessary to structure the fatty phase, meaning the
photostability of UVB filter and to reduce the particle release upon oil phase, to limit its exudation from solid compositions
immersion (39, 40). and its migration after application. It has been found
All these results demonstrate the interest of gelled that the use of organogelators combined with particular
nanoparticles and their aqueous dispersion for the polymers, allowed to structure oil-based phases (41, 43).
preparation of new formulations for cosmetic applications Gels obtained are more or less solid, and have a good
and dermo-cosmetic applications. mechanical strength, an acceptable rheology and an
enhanced heat stability (44).
PLO organogels as vehicles for anti-cellulite ingredients Perez et al. presented a fluid cosmetic composition for care
Cellulite leads to vascular, structural and hypertrophic or make-up of the lips associate a polyester, a non-volatile
alterations in adipose tissue. This is due to changes in the silicone oil, and an organogelator (45). It is shown that the
conjunctive dermic and subcutaneous tissue. Studies use of a polyester with a silicone oil, associated with an
have been conducted to evaluate the properties of a organogelator leads to a creamy texture, with a long-lasting
delivery system made from a pluronic lecithin organogel brilliance and pleasant (not sticky) when applied on skin
formulation and two physiotherapeutic ingredients, Aloe or lips. The organogelator was chosen among dialkyl-N-
Vera and Hydrocotyle asiatica (41). PLO have been the acylglutamides, polyamides and their mixtures. The optimum
interest of many studies, and proved to be effective as a concentration of organogelator in this composition is
dermic, and transdermal vehicle of medication. PLO were between 0.1 and 5 wt%. The final composition is anhydrous.
formed with Pluronic F127™ (Poloxamer 407), isopropyl
palmitate, soy lecithin and water. Propolis organogel for treating wounds
The advantage of the organogel over hydrogels with Propolis is a hard resinous material derived by bees from plant
the same ingredients is that it facilitates the transdermal juices. It contains pollen, waxes, resins and a large amount of
penetration to a greater degree. It is important in the flavonoids (46). It exhibits significant antibacterial, antifungal
treatment of cellulite as the ingredients must be able to and sometimes antiviral properties, depending on the chemical
reach the deepest layer of the skin to act upon the cells composition and the geographic location. It has been widely
where fat is accumulated in the adipose tissue (41). use in traditional medicine for treatment of wounds and burns.
Pluronic lecithin organogels (PLO) containing 4 wt% of propolis
Organogels in antiperspirant gel formulation extract were developed, evaluated and designed for treating
A gelator of particular interest for many applications wounds (47). Various formulations have been realized,
is HSA. Many patents have been filed describing depending on the concentration of lecithin and pluronic; the

H&PC Today - Household and Personal Care Today, vol. 10(4) July/August 2015 19
Organogel-based cosmetic tablets
and capsules
There is a need in the field of
cosmetics to have alternative types
of containers, for example regarding
travel situation, where there are more
and more restrictions concerning
liquids containing in canyon baggage
and bag weight. Tablets and capsules
of cosmetic products as shower gel,
soap, perfumes or creams, seems to
be a good alternative to classical
containers. Hurwitz et al. presented
the development of cosmetic tables
or capsules soluble in water and able
to deliver the active ingredient, which
is in an inner cavity protected by an
outer shell. The outer shell can be an
effervescent ingredient (mixture of
citric acid and sodium bicarbonate),
Figure 8. Schematic representation of the soft focus effect on the skin and the SEM micrographs
of the DBS fusiform particles (49). a gelatin composition to encapsulate
the ingredients, a coating agent or
an organogel (50). It is described
topical formulation containing 3 wt% of lecithin and 20 wt% as noncrystalline non glossy thermoreversible solid materials
of pluronic has been evaluated as the best one in terms of composed of an organic liquid such as an organic solvent, a
effectiveness, showing a higher drug release, skin permeation mineral or a vegetable oil.
and antimicrobial activity compared to propolis suspension
in water. It can offer an alternative therapeutic way to treat
wounds and scars. CONCLUSION

Pseudopeptidic organogels for cosmetic applications In this paper, we have reviewed (i) different categories
Simple short peptidic sequences derived from natural amino of organogels based on the nature of: organic solvent,
acids have been studied as organogelators for a variety of organogelator and its intermolecular interactions in the
solvents (5). In general, the organogelling behavior is associated medium, (ii) conventional and novel methods of preparation,
with the presence of a central aliphatic spacer. The properties (iii) essential parameters for characterization of organogels
of the pseudopeptides can be modulated through the proper and (iv) recent applications in the cosmetic and dermo-
selection of amino acids and spacer. cosmetic field.
Specific applications for these types of gel in cosmetic Organogels present interesting advantages to transdermal
formulations include the location where the products are delivery systems, especially for cosmetic agents, thanks
applied as creams or gels, in order to increase contact time to their inherent stability, non-irritation, excellent skin
and ease their topical application. Gels with high transparency moisturization, spreadability and ease of preparation and
and stability are obtained from low concentrations of administration. Over the last decade, the interest has been
organogelators. They have a great biocompatible potential. increased in development of organogels for various cosmetic
Few instances of amino acids derived gelling agents for applications including make-up, care of skin, nails, hair,
cosmetic applications are currently stated in the literature, lips, antiperspirant, anti-cellulite, etc. Novel systems such as
some organogelators with a bisamide structure based on organogel nanospheres, orgalogelator fusiform particles and
different diamines and fatty acid is described by Luis et al (48). organogel-based tablet and capsule have been designed for
Amides of stearic acid with ethanolamine or ethylene diamide delivering cosmetic agents and the results obtained are very
have been used for the preparation of toilet oil bars that enable impressive. Important progress is also observed in the field of
the release of oil when wetted water. organogelators with the arrivals of new generation of LMOGs
like pseudopeptidic LMOGs or supramolecular self-assembling
Diffusing particles based on organogelling xerogel fibres POGs, which are potential ingredients for cosmetic and dermo-
In this case, the creation concerns particles in the form cosmetic applications.
of a mass, essentially constituted by a plurality of fibers of
organogelator (49). It is not strictly speaking an organogel
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