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Stability of Lipogels with Low Molecular Mass Gelators and Emollient Oils
Ricardo C. Pasquali a; Natalia Sacco a;Carlos Bregni a
a
Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de
Buenos Aires, Buenos Aires, Argentina

Online publication date: 23 March 2010

To cite this Article Pasquali, Ricardo C. , Sacco, Natalia andBregni, Carlos(2010) 'Stability of Lipogels with Low Molecular
Mass Gelators and Emollient Oils', Journal of Dispersion Science and Technology, 31: 4, 482 — 487
To link to this Article: DOI: 10.1080/01932690903212263
URL: http://dx.doi.org/10.1080/01932690903212263

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Journal of Dispersion Science and Technology, 31:482–487, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0193-2691 print=1532-2351 online
DOI: 10.1080/01932690903212263

Stability of Lipogels with Low Molecular Mass Gelators


and Emollient Oils
Ricardo C. Pasquali, Natalia Sacco, and Carlos Bregni
Departamento de Tecnologı́a Farmacéutica, Facultad de Farmacia y Bioquı́mica, Universidad de
Buenos Aires, Buenos Aires, Argentina

The influence of preparation methods on stability of lipogels was studied. The objectives of this
study were to evaluate the ability of different low molecular solid ingredients used as excipients
in pharmaceutical and cosmetical products to form lipogels with emollient liquids of different
polarities as well as to evaluate the stability of the lipogels obtained and the spreading ability
of stable lipogels. The lipogels were prepared by heating the mix of oil and gelator a 100 C with
two different forms of cooling: slow cooling of the without stirring and quick cooling with stirring.
The stability tests were one year of storage at room temperature, centrifugation and three months
at 40 C. None of the lipogels prepared with slow cooling and without stirring were stable in
all stability tests. Eight of the formulations with quick cooling and stirring were stables in all
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stability tests: six with 12-hydroxystearic acid, one with hydrogenated castor oil, and one with
beeswax as gelators. The lipogels with 12-hydroxystearic acid as gelator do not spread on skin
or form clusters that spread after pressing with the fingers. The two lipogels with castor oil have
good spreading ability on the skin.
Keywords Emolients, gelators, gels, lipogels, organogels

INTRODUCTION networks obtained through a sharp solution (or sol) to


Organogels are semisolids systems formed by a gelator gel phase transition at a specific temperature are ‘‘strong’’
and an organic liquid. Organogels of lipophilic liquids gellike systems. ‘‘Strong’’ or solid matrix gels[3] with perma-
are denominated lipogels or oleogels. An organogel is nent solidlike networks in which the nodes are spatially
usually prepared by warming a gelator in an organic liquid extended (pseudo) crystalline microdomains. In the second,
until the solid dissolves, and then cooling the solution materials exhibiting a liquidlike viscoelastic behavior which
(or sol) to bellow the transition temperature.[1] The gela- are made of transient networks are termed ‘‘weak’’ gellike
tor’s aggregates are linked in complex, three dimensional systems. ‘‘Weak’’ or fluid matrix gels[3] with transient net-
networks that immobilize the liquid.[2,3] works exhibiting no elasticity over long periods of time,
Organogels can be divided based on the nature of in which the nodes are entanglements or spatially limited
the gelator in polymeric and low molecular mass organic organized microdomains.[1] The vast majority of low mol-
gelators. Polymers immobilize the organic solvent by form- ecular mass organic gelators assemble into solid networks
ing a network of either cross-linked or entangled chains for when added to appropriate organic solvents.[3] Fluid
chemical and physical gels, respectively.[3] Low molecular matrices are formed upon the incorporation of polar sol-
mass organic gelators posses a relative molecular mass vents to organic solutions of surfactants, which results in
below 3000.[4] These gels are viscoelastic solidlike materials, the reorganisation of surfactant molecules into mono or
possessing both the elastic properties of ideal solids and the bilayer cylindrical aggregates that immobilize the solvent.
viscous properties of newtonian liquids.[5] An extensively investigated biocompatible organogels in
Two different types of three-dimensional networks and drug delivery are formed by sorbitan monostearate[2] and
viscoelastic materials can be obtained in organogel systems. sorbitan monooleate[6] as gelators. Anhydrous gels were
In the first, materials exhibiting a solidlike, viscoelastic, obtained by dissolving low concentrations (1–10%) of the
mechanical behavior and which are made of permanent gelator in liquid alkanes, isopropyl myristate and various
vegetable oils at 60 C. Subsequent cooling of the system
yielded white thermoreversible gels at room temperature.[3]
Received 2 December 2008; accepted 31 December 2008.
Realdon et al.[7] prepared lipogels of peanut oil gellified
Address correspondence to Ricardo C. Pasquali, Departa-
mento de Tecnologı́a Farmacéutica, Facultad de Farmacia y with white beeswax, a mixture of partial glycerides and
Bioquı́mica, Universidad de Buenos Aires, Junı́n 956, 6 piso esters of long chain fatty acids, glyceryl monostearate, a
(1113) Buenos Aires, Argentina. E-mail: rcpasquali@yahoo.com mixture of mono and diglycerides of palmitic and stearic

482
LIPOGELS WITH LOW MOLECULAR MASS GELATORS 483

acids, and polysiloxane polyalkylene copolymer. The lipo- Preparation of Lipogels


gels were gelled in two different conditions: cooling to
By Slow Cooling without Stirring. The ingredients
room temperature and cooling at 35 C under continuous
were weighted in 20 cm3 transparent glass vials with a plas-
stirring and maintaining the preparations undisturbed at
tic cap and warmed at 100  2 C until total fusion of gela-
room temperature. Realdon et al. noted that these differ-
tor. The warmed glasses were shaked for homogenize and
ences in processing conditions may change the consistency
then cooling to room temperature on a heat insulating sur-
and the rheological behavior of the lipogels. They attribute
face, at rest and without extra refrigeration (mean cooling
these differences to the shape and dimension of the crystal-
velocity before gelation approximately 5 C=min). Two
lites of the solid fraction and their ordering in three-
samples of each formulation were prepared.
dimensional structure. In a posterior study, Realdon,
Ragazzi, and Ragazzi[8] observed considerable differences By Quick Cooling with Stirring. Lipogels were pre-
in rheological characteristics when prepared lipogels by pared in a same way that previous, except that the cooling
gelling olive oil with mono and diglycerides at rest, under was performed by stirring with a magnetic bar of 12 mm in
stirring, and milled after gelling. length and refrigeration with a water bath at 25 C (mean
Almeida and Bahia[9] where evaluated the physical stab- cooling velocity before gelation approximately 40 C=
ility of two lipogels (sweet almond oil gellified with sorbi- min). Two samples of each formulation were prepared.
tan monostearate and liquid paraffin with cholesterol)
using three different methodologies: at different tempera-
Physical Stability
tures (20 C and 40 C) over a 3-month period, an acceler-
The vials were stored lying down 30 days at room tem-
ated test performed where the temperature changed
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perature. It was observed gels formation and liquid separ-


between 4 C and 40 C every 24 hours during 7 days and
ation. A lipogel is considerate unstable with a minimum
rheological tests. In the remaining consulted bibliography
separation of liquid. A portion of the stable lipogels (1 g)
there is not mention about physical stability studies of
was centrifuged (30 minutes at 2500 rpm). The remain of
lipogels.[2,6–8,10–19]
the stable lipogels were stored additional eleven months
The objectives of this study are: 1) to evaluate the ability
at room temperature and the duplicates three months at
of different low molecular solid ingredients that are used as
40  2 C.
excipients in pharmaceutical and cosmetical products to
form lipogels with emollient liquids of different polarities;
2) to evaluate the stability of the lipogels obtained.
RESULTS AND DISCUSSIONS
The results of the stability tests are showing in Tables 1
MATERIALS AND METHODS through 4.

Materials
Isopropyl myristate, decyl oleate (Cetiol V), octyldode- Lipogels Prepared with Slow Cooling
canol (Eutanol G), glycerol monostearate (Cutina MD), and without Stirring
ethylene glycol distearate (Cutina AGS), dicaprylyl carbon- Mineral oil, dicaprylyl carbonate, cetyl isononanoate,
ate (Cetiol CC), 2-propylheptyl caprylate (Cetiol Sensoft) and 2-propylheptyl caprylate do not produce lipogels that
and cetyl isononanoate (Cetiol SN) were provided by are stables after 30 days at room temperature.
Cognis. Hydrogenated castor oil and 12-hydroxystearic Isopropyl myristate gelify without liquid separation with
acid are from Castoroil (Argentina) and sorbitan mono- 12-hydroxystearic acid. The lipogel is stable by centrifuga-
stearate (Span 60) was provided by Uniquema (Argentina). tion and unstable after one year at room temperature and
Beeswax, paraffin, and mineral oil meets the requierements three months at 40 C.
of Farmacopea Argentina VI. Decyl oleate and octyldodecanol gelifyes without liquid
separation with ethylene glycol distearate. This lipogels are
unstable by centrifugation and after one year at room tem-
Methods perature and three months at 40 C.
Composition of Lipogels Castor oil gelify without liquid separation with glycerol
Lipogels were composed by 9.00 g of oil and 1.00 g of monostearate, beeswax and ethylene glycol distearate. This
gelator. The oils were mineral oil, isopropyl myristate, lipogels are stables by centrifugation. The lipogel with
decyl oleate, castor oil, octyldodecanol, dicaprylyl carbon- beeswax is the only stable after one year at room tempera-
ate, and cetyl isononanoate and the gelators were paraffin, ture and the three are unstable after three months at 40 C.
hydrogenated castor oil, glycerol monostearate, beeswax, Not one lipogels prepared with slow cooling and with-
ethylene glycol distearate, and 12-hydroxystearic acid. out stirring are stables in all stability tests.
484 R. C. PASQUALI ET AL.

TABLE 1
Stability of lipogels after 30 days of storage at room temperature: G ¼ gel, GL ¼ gel and liquid; up: slow cooling
without stirring; down: quick cooling with stirring
Gelator Glycerol Ethylene glycol 12-Hydroxystearic Hydrogenated Sorbitan
oil Paraffin monostearate Beeswax distearate acid castor oil monostearate

Mineral oil L GL L GL GL GL GL
L GL GL GL G GL GL
Dicaprylyl L L L GL GL GL GL
carbonate GL GL GL GL G GL GL
Isopropyl GL LS LS GL G GL GL
myristate GL GL GL GL G GL GL
Cetyl L GL GL GL GL GL GL
isononanoate GL GL GL GL G GL GL
2-Propylheptyl L L L GL GL GL GL
caprylate L GL GL GL G G L
Decyl oleate GL GL GL G GL GL GL
L GL GL GL G G GL
Castor oil GL G G G GL GL L
G G G GL GL G L
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Octyldodecanol GL GL GL G GL GL LS
GL GL G GL GL GL LS

Lipogels Prepared with Quick Cooling and Stirring 2-Propylheptyl caprylate and decyl oleate gelifyes
Mineral oil, dicaprylyl carbonate, isopropyl myristate without liquid separation with hydrogenated castor oil
and cetyl isononanoate gelifyes without liquid separation and 12-hydroxystearic acid. The lipogels with 12-
only with 12-hydroxystearic acid. The formed lipogels are hydroxystearic acid are stables in all stability tests, but with
stables in all stability tests. hydrogenated castor oil are unstable by centrifugation.

TABLE 2
Stability at centrifugation of lipogels that are stable after 30 days of storage at room temperature: G ¼ gel,
GL ¼ gel and liquid, — ¼ unstable after 30 days of storage at room temperature; up: slow cooling without stirring;
down: quick cooling with stirring
Gelator Glycerol Ethylene glycol 12-Hydroxystearic Hydrogenated Sorbitan
oil Paraffin monostearate Beeswax distearate acid castor oil monostearate

Mineral oil —
G
Dicaprylyl —
carbonate G
Isopropyl myristate G
G
Cetyl isononanoate —
G
2-Propylheptyl — —
caprylate G GL
Decyl oleate GL — —
— G GL
Castor oil — G G G —
G G G — G
Octyldodecanol — GL
G —
LIPOGELS WITH LOW MOLECULAR MASS GELATORS 485

TABLE 3
Stability after one year of storage at room temperature of lipogels that are stable after 30 days of storage at room
temperature: G ¼ gel, GL ¼ gel and liquid, — ¼ unstable after 30 days of storage at room temperature; up: slow
cooling without stirring; down: quick cooling with stirring
Gelator Glycerol Ethylene glycol 12-Hydroxystearic Hydrogenated Sorbitan
oil Paraffin monostearate Beeswax distearate acid castor oil monostearate

Mineral oil —
G
Dicaprylyl —
carbonate G
Isopropyl GL
myristate G
Cetyl isononanoate —
G
2-Propylheptyl — —
caprylate G G
Decyl oleate GL — —
— G G
Castor oil — GL G GL —
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GL G G — G
Octyldodecanol — GL
GL —

Castor oil gelify without liquid separation with paraffin, temperature and at centrifugation and unstable after one
hydrogenated castor oil, glycerol monostearate and bees- year at room temperature and three months at 40 C. With
wax. With paraffin is stable over at least 30 days at room glycerol monostearate is unstable after three months at

TABLE 4
Stability after three months at 40 C of lipogels that are stable after 30 days of storage at room temperature: G ¼ gel,
GL ¼ gel and liquid, — ¼ unstable after 30 days of storage at room temperature; up: slow cooling without stirring;
down: quick cooling with stirring
Gelator Glycerol Ethylene glycol 12-Hydroxystearic Hydrogenated Sorbitan
oil Paraffin monostearate Beeswax distearate acid castor oil monostearate

Mineral oil —
G
Dicaprylyl —
carbonate G
Isopropyl GL
myristate G
Cetyl —
isononanoate G
2-Propylheptyl — —
caprylate G G
Decyl oleate GL — —
— G G
Castor oil — GL GL GL —
GL GL G — G
Octyldodecanol — GL
GL —
486 R. C. PASQUALI ET AL.

TABLE 5
Spreading ability on the skin by pressing with the fingers of lipogels prepared with quick cooling and stirring
that passes all stability tests
Oil Gelator Spreading ability

Mineral oil 12-Hydroxystearic acid Form clusters that spreads after pressing
Dicaprylyl carbonate 12-Hydroxystearic acid Not spread
Isopropyl myristate 12-Hydroxystearic acid Form clusters that spreads after pressing
Cetyl isononanoate 12-Hydroxystearic acid Not spread
2-Propylheptyl caprylate 12-Hydroxystearic acid Form clusters that spreads after pressing
Decyl oleate 12-Hydroxystearic acid Form clusters that spreads after pressing
Castor oil Hydrogenated castor oil Good spreading
Castor oil Beeswax Good spreading

40 C. Lipogels with hydrogenated castor oil and beeswax 16.5 MPa0.5), in the meanwhile hydrogenated castor oil
are stables in all stability tests. and beeswax forms stables lipogels with the more polar
Octyldodecanol gelifyes without liquid separation with castor oil (solubility parameters ¼ 18.2).
beeswax. The formed lipogel is unstable after one year at The resistance to spread of the lipogels with 12-
room temperature and three months at 40 C. hydroxystearic acid could be attributed to the rigidity of
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Eight formulations are stables in all stability tests: six the gel network and the good spread ability of the lipogels
with 12-hydroxystearic acid, one with hydrogenated castor of castor oil gellified by hydrogenated castor oil and bees-
oil and one with beeswax as gelators. The lipogels with wax to the minor rigidity of the gel network. Due to its
12-hydroxystearic acid as gelator don’t spread or form good spread ability, the lipogels of castor oil gellified by
clusters that spread after pressing. The two lipogels with hydrogenated castor oil and beeswax are the more
castor oil has a good spreading ability (Table 5). adequate for topical application of lipophilic drugs.
The ability of 12-hydroxystearic acid to form stable lipo-
gels could be able to the hydroxyl group in the atom of car-
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