Documente Academic
Documente Profesional
Documente Cultură
ISSN 2349-7750
PHARMACEUTICAL SCIENCES
Abstract:
The present work was carried out with the grail of formulating a gellified emulsion of lycopene, an anti-oxidative
agent. The distinctive feature of topical drug delivery system is the direct accessibility of the skin as a target organ
for diagnosis and treatment. Emulgels have emerged as one of the most prevailing drug delivery systems for the
delivery of hydrophobic drugs owing to their dual control release system i.e. gel and emulsion. Lycopene, as a
natural source of anti-oxidants, has enamoured attention due to its biological and physicochemical properties. It is
completely insoluble in water, so to overcome this limitation, an emulsion based approach was being used so that
even this hydrophobic moiety can enjoy the unique property of gels. Lycopene, an anti-oxidative agent, has been
used in the treatment of various oxidative diseases. This pigment protects the cells against damage from the free
radicals formed when body cells burn oxygen for energy. In order to decrease the oxidative reactions with skin i.e.
to treat acne vulgaris, lycopene emulgel was developed. This work was conducted to develop an emulgel of lycopene
using three different gelling agents i.e. Carbopol 934P, HPMC LV-15 and NaCMC. Oleic acid was used as a
penetration enhancer. The gellified emulsions were characterized for their physical appearance, rheology,
spreadability, drug content and stability. In-vitro release studies were conducted to check the drug release through
egg membrane. The formulations were evaluated for their antioxidant activity as well as their acute skin irritation
potential. Formulation F1 was found to have fallen within the stipulated criteria of all the evaluation parameters.
Hence, it was concluded that formulation F1, containing carbopol 934P (1% w/w), was the optimized formulation. It
exhibited the maximum drug release and antioxidant activity, in addition to the least skin irritation potential.
Keywords: Lycopene, Emulgel, Gelling agents, Anti-oxidant, gellified emulsion.
Please cite this article in press as A. Kumari et al, , Formulation and Evaluation of Lycopene Emulgel , Indo
American J of Pharm Sci, 2015;2(6).
Stability of solution Then, the pH was measured. The test was performed
The stock solution of lycopene was kept for 24 hours in triplicate using a digital pH meter and the mean ±
to assess any possible degradation and again the SD was calculated.
calibration curve was plotted. There was no
difference in the slope of both the calibration curves Spreading Coefficient
at 0 and 24 hours. Spreading coefficient was determined by the
apparatus suggested by Multimer et al (1956). It
Preparation of Lycopene Emulgel consists of a wooden block, which is attached to a
The steps involved in the preparation of the gellified pulley at one end. Spreading coefficient was
emulsion include the preparation of the emulsion measured on the basis of ‘slip’ and ‘drag’
phase, followed by the addition of the emulsion into characteristics of emulgel. A ground slide was fixed
an aqueous solution of the gelling agent, to form a on the wooden block. An excess of emulgel (about 2
semisolid formulation. The oil phase of the emulsion gm.) under study was placed on this ground slide.
was prepared by dissolving the lipophillic surfactant Emulgel preparation was then sandwiched between
(span 80) in olive oil while the hydrophilic surfactant this slide and second glass slide having same
(Tween 80) was dissolved in de-ionized water to dimension as that of the fixed ground slide. The
obtain the aqueous phase. The selection of oil for second glass slide is provided with the hook. Weight
preparation of lycopene emulgel was based on of 1 kg was placed on the top of the two slides for 5
solubility studies conducted initially using different min to expel air and to provide a uniform film of
oils such as light liquid paraffin, eucalyptus oil, clove emulgel between the two slides. Measured quantity
oil and olive oil. A clear homogenous solution of weight was placed in the pan attached to the pulley
resulted using olive oil and lipophillic surfactant span with the help of hook. The time (in sec) required by
80. In formulations F1, F2 and F3 the gel bases were the top slide to move a fixed distance was noted. A
prepared by dispersing carbopol 934P in de-ionized shorter interval indicates better Spreading coefficient.
water with constant stirring at a moderate speed using It is calculated by using the formula:
magnetic stirrer. Formulations F4, F5 and F6 were S = M.L / T
prepared by using NaCMC as a gelling agent and
formulations F7, F8 and F9 were prepared by Where, M = weight tied to upper slide.
dispersing HPMC-LV15 in heated distilled water
(75oC) and the dispersion was cooled and left L = length of glass slides/distance of travel.
overnight. The pH of all the formulations was
adjusted to 5.5 to 6.5 using triethanolamine. Methyl T = time taken to travel a fixed distance.
and propyl paraben were dissolved in propylene
Rheology
glycol and mixed with aqueous phase. Lycopene,
The viscosity of the formulated batches was
being hydrophobic was dissolved in oil phase. Oleic
determined using a Brookfield Viscometer with
acid was also mixed in oil phase as a penetration
spindle 96. The formulation whose viscosity was to
enhancer. Both the oil and aqueous phases were
be determined was placed in the beaker and was
separately heated to 70oC to 80oC, then the oily phase
allowed to settle down for 30 min. at room
was added to the aqueous phase with continuous
temperature before the measurement was taken.
stirring and allowed to cool to room temperature. The
Spindle was lowered into the centre of Emulgel
prepared emulsion was mixed with the gel in 1:1 ratio
taking care that spindle does not touch bottom of the
with gentle stirring to prepare the emulgel. The
beaker and rotated at a speed of 10, 20, 50 and 100
formulation composition of different batches of
rpm. The viscosity reading was noted down and the
lycopene emulgel is presented in Table 6.
averages of three readings were taken.
Physical examination
Extrudability
The prepared gellified emulsions were inspected Extrudability test is based upon the determination of
visually for their color, appearance and homogeneity. the weight required to extrude 0.5 cm ribbon of
emulgel in 10 seconds from lacquered collapsible
pH Determination aluminum tube. The test was performed in triplicate
The pH of the prepared gellified emulsion was and average values were calculated using the
determined by using a digital pH meter. 1 gm of the following formula.
gellified emulsion was stirred in distilled water, until Extrudability=Weight applied to extrude emulgel
a uniform dispersion was formed. It was kept aside from tube (gm)/area (cm2)
for 2 hours. The volume was then made up to 100 ml.
0.15 ml of chloroform is required to dissolve 50 mg of lycopene; hence, it is justified that 15 ml of chloroform shall
be used as medium in receptor compartment of Franz diffusion Cell for release studies. 2.95 parts of chloroform are
required to solubilize 1 part of lycopene; hence, lycopene is freely soluble in chloroform and can be suitably used
for determination of drug content in suitably prepared emulgel formulations. The solubility of lycopene is presented
in Table 2.
The melting point of lycopene was found to be 171oC which is within the reported range hence the sample of
lycopene is free of impurities (Table 3).
Solvent Solubility Volume of the medium required Parts of the solvent required
to dissolve one dose of the drug to dissolve one part of the
(mg/ml) (ml) drug
Chloroform 338.57 0.15 2.95
Wavelength (nm)
Beer’s law was obeyed over the concentration range (Fig. 4) were found to be 0.0007 and 0.007
of 20 to 90 µg/ml at 483.5 nm wavelength for respectively with correlation coefficient of 0.999.
lycopene. The slope and intercept of calibration curve
Batch code F1 F2 F3 F4 F5 F6 F7 F8 F9
Oil phase Lycopene 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05
Oleic acid 2 2 2 2 2 2 2 2 2
Olive oil 4 4 4 4 4 4 4 4 4
Spans 80 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Aqueous Propylene glycol 5 5 5 5 5 5 5 5 5
phase
Tween 80 1 1 1 1 1 1 1 1 1
Methyl paraben 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03
Propyl paraben 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03
Gel phase Carbopol 934P 1 1.25 1.5 - - - - - -
Sodium CMC - - - 5 5.5 6 - - -
HPMC-LV15 - - - - - - 6 7 8
Water q. s. q. s. q. s. q. s. q. s. q. s. q. s. q. s. q. s.
Triethanolamine was added to adjust pH of all the formulations from 5.5 to 6.5
The prepared gellified emulsions were pink, viscous, formulation diminishes as the concentration of
and creamy preparations, with a smooth and polymer increases, as given in Table 7.
homogenous appearance. The pink color of
The pH of all the gellified emulsions was found to be increase in concentration of polymers: Carbopol
in the range of 5.9 to 6.6, which lies in the normal pH 934P, NaCMC and HPMC-LV15 a significant
range of the skin. The results are shown in Table 8. decrease (p≤0.05, df 2 and 6, Fcrit= 5.143, F=
The spreadability indicates the ease with which 722896.2 for Carbopol 934P, F=66.102 for NaCMC
emulgel is spreadable by the amount of shear. From and F=174.699 for HPMC LV-15, single factor
Figure 5 it is clear that the spreading coefficient for ANOVA) was noted in the spreadability of the
the prepared lycopene emulgel formulation in the prepared emulgel formulations. The spreadability is
descending order was very important since it shows the behaviour of the
F1>F7>F8>F9>F2>F4>F5>F3>F6. Formulation F1 emulgel when it comes out from the tube.
gave the highest value for spreadability. The effect of Spreadability coefficient of prepared lycopene
various polymers on spreading coefficient is shown emulgel is shown in Table 9 and Figure 7.
in Figure 9. From Figure 8, it is seen that with
Table 8: pH of Prepared Lycopene Emulgel
The viscosity of the prepared lycopene emulgel was emulsions. While F3 was the most viscous
found to increase in general with increase in formulation, F7 had the least viscosity. It is seen from
concentration of gelling agent. The effect of rpm on Fig. 10 that increase in concentration of gelling
viscosity is depicted in Figure 9. It is seen that there agents results in a significant (p≤0.05, df 2 and 6,
is a shear thinning effect, that is, the viscosity falls on Fcrit=5.143, F=101942.9 for Carbopol 934P, p≤0.05,
increasing shear rate from 10 to 50 rpm. All the df 2 and 6, Fcrit=5.143, F=1385288 and p≤0.05, df 2
prepared formulations possessed optimum viscosity. and 6, Fcrit=5.143, F=158027.1, single factor
Inclusion of different gelling agents in different ANOVA) increase in viscosity of formulations. The
concentrations seems to have brought about a viscosity of the prepared emulgel at 20 rpm is
noticeable difference in the viscosity of the gellified depicted in Table 10 and Figure 8
The extrudability of the prepared lycopene emulgel viscosity of the gellified emulsion increases which
was found to vary from 2.34±0.27 gm/cm2 to leads to decrease in the extrudability of the lycopene
20.7±2.6 gm/cm2. Figure 12 depicts the effect of emulgel. Decrease in extrudability implies
concentration of gelling agent on extrudability of application of higher weight/area to extrude the gel
prepared lycopene emulgel. It is seen that with which correlates to the higher viscosity of the
increase in concentration of Carbopol 934P and formulation. The results are shown in Table 11 and
HPMV LV-15 there is a significant (p≤0.05; df 2 and Figure 11.
6; Fcrit=5.143; F=6.655, p≤0.05, df 2 and 6;
Fcrit=5.143; F=113.317, single factor ANOVA))
decrease in extrudability whereas in case of NaCMC
there is no any significant (p≤0.05; df 2 and 6;
Fcrit=5.143; F=13.57, single factor ANOVA) decrease
or increase in extrudability. As we increase the
concentration of gelling agents consequently the
Table 11: Extrudability of Lycopene Emulgel
Batch code Extrudability Batch code Extrudability
(gm/cm2)* (gm/cm2)*
F1 14.2±1.9 F6 3.80±0.38
F2 18.5±2.1 F7 12.02±0.51
F3 20.7±2.6 F8 7.31±1.5
F4 2.34±0.27 F9 2.73±0.61
F5 2.45±0.47
* Data indicates mean± S.D. of triplicate determinations
From the above results it was found that the drug batches is greater than 0.5, hence, it is clear that all
release was best fit to Korsmeyer Peppas model for the formulations are showing non-Fickinian and
F2, F3, F7, F8 and F9 since highest value of r for the anamolous diffusion.
formulations was seen and Higuchi model for
formulation F1, F4, F5 and F6. The ‘n’ value for all
Table 14: Model Fitting For Release Kinetics Of Prepared Lycopene Emulgel
Batch Release models Best fit model
Fig 14: In-vitro Release of Lycopene from the Prepared Emulgel in 240 min
Fig. 15: Effect of Concentration of Gelling Agent on Release of Lycopene at 4th hour
Fig.16: Micrograph of Egg Membrane After Soaking In Fig.17: Micrograph of Egg Membrane after In-
Dissolution Media Overnight Chloroform Vitro Release Study
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