International Journal of Drug Delivery 6 (2014) 113-120

http://www.arjournals.org/index.php/ijdd/index

Original Research Article

ISSN: 0975-0215

Preparation and Evaluation of Curcumin Invasomes

Lakshmi PK1, Mounica V1, Manoj Kumar Y1, Prasanthi D1
*Corresponding author:
Lakshmi PK
1Department

of Pharmaceutics, G.Pulla
Reddy College of Pharmacy,
Hyderabad, India.

Abstract
Curcumin has poor aqueous solubility and has bioavailability problems. Hence in the present study
the solubility of curcumin was increased by complexing with cyclodextrin (CD) and Hydroxy propyl
cyclodextrin(HPCD). This complex is incorporated in to invasomes and then into HPMC gel to
prepare as a transdermal formulation.Curcumin cyclodextrin complexes were prepared by physical
mixture and co-precipitation method. Different formulations of invasomes containing 0.5, 1.0, 1.5 %
of limonene, fenchone, nerolidol individually were prepared using mechanical dispersion technique.
Invasomes were characterized for vesicular size, surface morphology, zeta potential, entrapment
efficiency and percutaneous permeation.Formulations CHL1 and CHL2 were optimized for further
studies. It was found in the study that complex with HPCD in 1:2 proportion prepared by coprecipitation method was found to bind 90% of curcumin.Invasomal preparation with 0.5% limonene,
4% ethanol was found to enhance permeation by 8.11 times the control.In vivo diffusion studies
were conducted using franz diffusion cell, ex vivo skin permeation studies of CHL1using rat
abdominal skin showed cumulative drug permeated (Q24)of 70.32 g/cm2, steady state transdermal
flux of 3.344 g/cm2/hr-1, permeability coefficient of 5.35 cm/hr and lag time of 1 hr when compared
with control formulation. From the results it was concluded that the solubility of curcumin increased
by complexing with HPCD and invasomal preparation with 0.5% limonene has improved
permeation through the skin.
Keywords: - Curcumin, Cyclodextrin, Invasomes, HPMCK4M gel

Introduction
Curcumin known as diferuloylmethane a yellow polyphenol is an
extract from rhizomes of Curcuma longa lin. This compound has
potency against many diseases such as cough, diabetes, anorexia,
alzheimer disease, rheumatism, hepatic disorders, antioxidant,
anti-inflammatory, anti carcinogenic, hypocholesterolemic,
antibacterial, antispasmodic, anticoagulant, anti tumor etc.
[1].Although therapeutic properties of curcumin have been the topic
of several studies widespread clinical applications of curcumin is
limited due to its poor aqueous solubility, degradation at alkaline
pH, photodegradation, low systemic bioavailability. Cyclodextrins
are 1,4 linked cyclic oligosaccharides produced by enzymatic
conversion of starch and contain atleast 6 D - (+) glucopyranose
units. -CDsare insufficient in size for many drugs while -CDsare
expensive. Usually -CD has been used extensively for many
studies because of its ready availability, cavity size and use with
wide range of drugs. Cyclodextrins are used pharmaceutically for
drug complexation, as solubilizers, diluents, bioavailability
enhancers for poorly soluble drug [2]. Serum plasma levelswere
found to be only 2.25g/ml by intra peritoneal route and 0.36g/ml
by intravenous route [3, 4]. Curcumin was complexed with cyclodextrin using co-precipitation method to increase the
solubility[5]. Anand et al., coated that nanoparticles, liposomes,

phospholipid complexes are promising novel formulations which

improve the bioavailability [6]. Transdermal route is the alternate
pathway for localized or systemic pharmacological effects.
Although advantageous in avoiding problems of poorly absorbable
drugs and enzymatic degradation, penetration through the stratum
corneum (SC) of epidermis an efficient barrier is the major
problem. Hence several techniques and carrier systems were
developed to cross this barrier.Liposomes,phospholipid vesicles
are used as drug carriers. Traditional liposomes can be used only
for topical application but they cannot deeply penetrate the skin
and are restricted to upper layers of SC [7].Hence a series of
vesicular carriers transferosomes with edge activators,
ethosomes with high amounts of ethanol, invasomes with ethanol
and terpenes were developed. Elastic vesicles have shown to be
superior in enhancing the penetration than conventional gel state
and even liquid state vesicles [8]. Terpenes like cineole, citral and
limonene are widely used for hydrophilic and lipophilic drugs.
Dragicevic-Curic et al., 2009preparedsemisolid liposomal
formulation by mixing with carbomer hydrogel to avoid leaky
behavior of liposomes on application site [8].Two proposed
mechanisms of penetration enhancement of terpenes observed are
permeation as intact vesicles and disruption of intercellular lipid
lamellae, forming channels[9].
Hence the present study deals with improving the solubility of
curcumin by complexing with CD or HPCD and then incorporating

This work is licensed under a Creative Commons Attribution 3.0 License.

Lakshmi et al. International Journal of Drug Delivery 6 (2) 113-120 [2014]

this complex mixture into vesicular carrier invasomes. This
vesicular carrier is then incorporated into HPMC K4M gel.
Invasomes are characterized for size, morphology, zeta potential,
stability. Invasomal gels are investigated for ex vivo permeation
studies.

entrapped is calculated indirectly from the amount of free drug from

the formula.

100

Materials and methods

Surface morphology

Materials

Surface morphology was studied by placing a drop of preparation

on a clear glass slide, air dried, coated with gold using sputter
coater (Polaron E5100, Watford, UK) and visualized under
Scanning electron microscope (Joel 5400, Japan).

Curcumin was procured from Sanat Products Limited, New Delhi,

Soya phosphatidylcholine-70 from Sonic-Biochem extractions,
limonene, fenchone and nerolidol procured from Alfa aesar, HPMC
K4M procured from Sigma labs, HPCD from Otto Kemi and other
analytical reagents.

Ex Vivo permeation studies

Ex vivo studies were approved by institutional animal ethics

1:1

43%

comittee. Abdominal skin section of male wistar rat was prepared

and permeation studies were performed using Franz diffusion cell.
Effective surface area of cell was 2.0 cm2 and has a receptor
volume of 20ml. Donor compartment was applied with invasomal
preparation and 20 ml of pH 7.4 phosphate buffer saline
maintained at 37C was used as receptor medium. Aliquot
amounts were withdrawn and replaced by fresh media to maintain
sink condition. Samples were analyzed using UV
spectrophotometer, steady state transdermal flux (g/cm2/hr),
permeability coefficient (cm/hr), enhancement ratio were
calculated.

1:2

61%

Preparation of Gel

1:1

65%

1:2

90%

1:1

24%

1:2

36%

Aqueous gel of 2% HPMC K4M was prepared by soaking the

polymer overnight, appropriate amounts of propylene glycol was
added and mixed until gel was formed. To this gel base optimized
invasomal suspension was added such that 500 mg of gel contains
12.5% curcumin.

1:1

43%

Speradability studies

1:2

54%

Spreadability was determined by measuring the spreading

diameter of 1g of gel between 20X20 cm glass plates for 1 min.
Mass of upper plate was standardized at 150g. It is calculated by
using the formula

Complexation of Curcumin
Curcumin was complexed with CD and HPCD according to the
formula (Table
1) by Physical Mixture and Co-precipitation
method (Zaibunnisa A.H et al., 2011)[5].
Table 1: Preparation and optimization of curcumin CD complex.
Drug:
Percentage
Carrier
Method
Carrier
bound
Physical Mixture
HPCD
Co-precipitation

Physical Mixture
CD
Co-precipitation

Preparation of invasomes
Optimized 1:2 co-precipitated complex of Curcumin and HPCD
was loaded in to invasomes by mechanical dispersion technique.
Soya Phosphotidylcholine (1 3% w/v) was added to ethanol and
vortexed for 5 minutes. Curcumin HPCD complex and different
terpenes (0.5 1.5%) were added under constant vortexing, this
mixture was sonicated for 5 minutes. Fine stream of Phosphate
buffer saline (upto 10%w/v) was added with syringe under constant
vortexing. It was vortexed for additional 5 minutes to obtain final
invasomal preparation.

Where S is spreadability, M is weight tied on upper glass plate, L is

length of glass slide, T is time in sec.

Extrudability
Extrudability was carried out by Pfizer hardness tester. 15g of gel
was filled in aluminium tube and plunger was adjusted to hold the
tube properly. Pressure of 1 Kg/cm2 was applied for 30 sec and the
mass of gel extruded was measured. This procedure is repeated at
three equidistance places of tube.

Entrapment efficiency

Skin irritant studies

Entrapment efficiency was studied by ultracentrifugation method.

1ml of invasomal suspension was transferred to Ephendroff tubes,
centrifuged at 15000 rpm, 4C for 15 min in two cycles to separate
the unentrapped drug and invasomes. Clear fraction was analyzed
for free drug at 430 nm spectrophotometrically. Percentage

Skin irritant studies were performed on 3 healthy rabbits.

Unbraided skin was cleaned with rectified spirit, control formulation
was placed on left dorsal surface and test formulation on right
dorsal surface. The formulation was removed after 24 hrs and the

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Lakshmi et al. International Journal of Drug Delivery 6 (2) 113-120 [2014]

skin was examined for erythema/edema and scored according to
primary dermal irritation index classification.

Stability studies
Optimized invasomal gel was sealed in 10 ml glass vial and stored
at refrigeration temperature (4 - 8C) and room temperature for one
month. Entrapment efficiency, physical appearance was
determined at regular intervals.

Results and Discussion

Characterization of curcumin complex
Physical mixture, co-precipitation methods using CD, HPCD in
two ratios 1:1 and 1:2 were used for complex preparation.
Complexes prepared by co-precipitation method showed more
bonding/ complexing than the physical method. It was found that
complexation in 1:1 ratio showed 43, 65% bonding by coprecipitation method with CD and HPCD respectively which
was more than 24, 43% prepared by physical mixing method.
Similarly with 1:2 ratio it was found to be 54, 90% with CD and
HPCD by co-precipitation method where as only 36, 61% by
physical mixing method. Complex prepared by co-precipitation
method in 1:2 ratio with CD showed complexation of only 54%,
where as HPCD showed 90%. Hence co-precipitation method
showed more bonding than physical method [5] and more bonding
was observed with 1:2 proportion.
Solubility of pure curcumin was found to be 2.98X10-11M and
increased to 1.63X10-8M in HPCD whereas only 0.21X10-8M with
CD. This is accounted because of hydrophilic nature of CD
derivative HPCD which enhanced the solubility of poorly water
soluble curcumin when compared to parent CD [10]. Hence
curcumin- cyclodextrin complexes prepared by co-precipitation
method using HPCD in 1:2 proportion was optimized.

Figure 1: Comparision of FTIR spectra.

FTIR spectral studies

Compatibility studies were performed using Fourier Transform
Infrared spectrophotometer (FTIR 8400s, Shimadzu, Japan) in the
range of 4000 400 cm-1 using potassium bromide pellet method.
Pure curcumin showed absorption peaks at 3504.46 cm-1
characteristic to hydroxyl ( OH) group, peak at 1601 cm-1
characteristic to C=C of benzene ring, 1506.31 cm-1 characteristic
to C=O, C=C, peaks at 1000 1260cm-1 for C-O and are found to
be near to the absorption bands [11]. The complexed mixture with
HPCD also showed peaks in the region of 3503.84, 1601.39,
1506.73cm-1(figure 1). Retention of the peak in the region 1601
shows that complexes were not formed with carbonyl group of
curcumin and increase in intensity around the region of C-O ether
bond shows that complexation was due to this C-O bond of
curcumin [5].

Figure 2: DSC of curcumin alonend curcumin complex

DSC studies
DSC studies were performed and exothermic peaks were observed
around the region of 170 180C [12] this was because of melting
of curcumin. The reduced intensity of the peak in complex of
curcumin with HPCD indicates complexation of curcumin (figure
2).

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Characterization of invasomes

In vitro studies

Entrapment efficiency

In vitro diffusion studies were carried out using dialysis membrane

to evaluate release from invasomes. Release profile for 24 hrs
study is shown in figure 3.Three terpene formulations CHL1, CHL2,
CHF2 showed good release rate of 22.313.0, 20.892.8,
15.251.9
respectively. In previous studies 1% terpene formulations showed
better release [13] but the results show that 0.5% limonene showed
good release than 1% formulation this may be attributed to
presence of ethanol in the formulations. These three formulations
were selected for ex vivo studies. Although CHF1 showed good
entrapment efficiency of 88.4 0.11 because of its release rate
compared to CHF2 it was not selected for further studies.

Invasomes were prepared by mechanical dispersion method.

Preliminary studies were conducted and 1% soya
phosphotidylcholine was optimized for further studies as it showed
maximum entrapment efficiency. Curcumin-HPCD was taken as
equivalent to 5mg and incorporated into invasomes with different
terpenes limonene, fenchone, nerolidol at 3 levels 0.5, 1, 1.5%
individually and 4% of ethanol was added to all the
formulations(table 2). Entrapment efficiency of each formulation
was calculated and it was found to be maximum inCHL193.50.08%, 88.40.11 in CHF1, 87.40.12 in CHL2, 76.80.07 in
CHF2 and least in CHN3 - 58.40.06. Entrapment efficiency with
different terpenes was found in the order limonene > fenchone
>nerolidol. Limonene showed highest entrapment efficiency which
is attributed due to the presence of hydrocarbon group.

Ex vivo skin permeation studies

Ex vivo studies were approved by IAEC. Permeation studies were
conducted using excised male wistar rat abdominal skin and were
performed usingFranz diffusion cell. Cumulative drug permeated
was found to be 70.321.98 for CHL1, 60.582.61 for CHL2,
51.83.02 for CHF2 which was found to be more than control
22.892.08. D. D. Verma et al., observed increase in permeation
with increase in ethanol [14],many literatures discusses the
increase in permeation with terpene loaded vesicles when
compared with liposome vesicles. Increased permeation in
formulation with terpenes than conventional liposomes (control)
may be attributed to synergistic effect of ethanol and terpenes as
formulation CE prepared without terpenes also showed increase in
permeation of 40.322.76 [7](table 2).

Surface morphology
Characterization of invasomes
Vesicular size
Vesicle size was determined using Microtel X100 Leeds & Northrup
particle size analyzer, UK and it was observed to be 134.7nm and
poly dispersity index was < 0.2 for CHL1.
Zeta potential
Zeta potential was measured at Malvern Instruments Ltd using
Zeta sizer and was found to be -33.7mv for CHL1. Negative charge
may be imparted due to the presence of ethanol [7,12].
90
80
%drugrelease

70
60

CHL1

CHL2

50

CHL3

CHF1

40

CHF2

CHF3

30

CHN1

CHN2

20

CHN3

10
0
0

10

15
Time(Hours)

20

25

30

Figure 3: Release profile of prepared invasomal formulations.

with CHL1 3.34 0.08 and increased flux of 3.02 0.07 with CHL2
and 2.28 0.16 with CHF2.

Penetration parameters like steady state transdermal flux and

permeability coefficient were calculated. Control formulation
showed flux of 0.410.14 g/cm2/hr, maximum flux was observed

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Lakshmi et al. International Journal of Drug Delivery 6 (2) 113-120 [2014]

JSS steady state flux, dM amount of drug permeated, S unit of

cross section, t time, CV total concentration in the donar
compartment, Kp permeability coefficient.
Permeability coefficient was found to be 5.350.03 X10-3 with
CHL1, 4.830.07X10-3, 3.660.06X10-3 with CHL2 and CHF2,
where as only 0.320.04X10-3 with control and 0.980.09 CE (with
out terpenes).

Enhancement ratio

Permeability
Coefficient
cm/hr)

ND

ND

22.89 2.08

0.41 0.14

0.32 0.04

3.6 0.12

CE

ND

ND

40.322.76

1.730.19

0.980.09

4.2

2.40.5

CHL1

0.5

93.5 0.08

22.31 3.0

70.32 1.98

3.34 0.08

5.35 0.03

8.11

1 0.2

CHL2

87.4 0.12

20.89 2.8

60.58 2.64

3.02 0.07

4.83 0.07

7.33

1.2 0.1

CHL3

1.5

82.2 0.06

19.34 2.4

ND

ND

ND

ND

ND

CHF1

0.5

88.4 0.11

14.26 1.0

ND

ND

ND

ND

Lag time
hrs

Nerolidol
(%)

Control

SSTF
g/cm2/hr

Fenchone
(%)

Cumulative
permeated
(Q24)g/cm2

(X10-3

drug

rate
Release
g/cm2/hr1/2

Entrapment efficiency
SD

Limonene
(%)

Formulation code

Table 2: Formulation and Evaluation results of Invasome preparations

CHF2

76.8 0.07

15.25 1.9

51.8 3.02

2.28 0.16

3.66 0.06

5.55

ND
1.9 0.6

CHF3

1.5

68.7 0.13

10.33 2.0

ND

ND

ND

ND

ND

CHN1

0.5

76.5 0.08

12.98 2.8

ND

ND

ND

ND

ND

CHN2

64.8 0.12

14.86 2.7

ND

ND

ND

ND

ND

CHN3

1.5

58.4 0.06

8.79 2.7

ND

ND

ND

ND

ND

CNT G

7.98 1.86

0.28 0.03

0.450.02

4.20.2

CHL1G

52.8 2.32

2.21 0.27

3.530.08

7.78

2.5 0.1

CHL2G

42.32 2.52

1.77 0.08

2.840.04

6.25

20.05

Curcumin Hydroxy propyl cyclodextrin complex 5 mg (5% w/v), Soya lecithin

Fenchone, N- nerolidol, ND- not determined, SSTF - Steady state transdermal flux.

1%, Ethanol

4% in all formulations except control, L-limonene, F-

The optimized invasomal suspension CHL1, CHL2 was

incorporated in to 2% HPMC K4M which was optimized by
preliminary trials. Prepared gel was inspected under black and
white background and was found very clear and without any
aggregates.
The pH of the gel was determined using digital pH meter LI 127
Elico. 0.5g of gel was dispersed in 100 ml of pH 7.4 Phosphate
buffer and checked for its pH. It was found to be 6.9, 7.0 for CHL1,
CHL2 respectively.
Spreadability and Extrudability were performed as mentioned
earlier and spreadability was found to be 27.07cm, 24.96cm for
CHL1, CHL2 respectively, and extrudability was found to be
excellent.
Viscosity was measured using LV DV-II+Pro Brookfield
programmable viscometer with spindle 64, and was found to be
39822cp, 38961cp with CHL1, CHL2 respectively.

Enhancement ratio was calculated by comparing the formulations

CHL1, CHL2, CHF2 with Control. CHL1 was found to enhance by
8.11 time and only 7.33, 5.55 times with CHL2, CHF2 respectively.
T. Subongkot et al. also reported enhancement of 6.8 8 folds in
ultradeformable vesicles compared to liposomes [9]. Lag time
decreased with the use of terpenes when compared with control
from 3.60.12 for control to 10.2, 1.20.1, 1.90.6 for CHL1,
CHL2, CHF2 respectively owing to increased permeation effect of
terpenes. Permeation enhancement of present study are in
controversy with other authors but are according to the results of
work of A. F. El-kattan et al., 2001 [16] where limonene showed
high entrapment with lipophilic drugs. The increase in the
permeation observed with limonene may be due to its lipophilicity
and low boiling point [17] and lipophilic nature of curcumin.

Organoleptic characterization of gel

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Lakshmi et al. International Journal of Drug Delivery 6 (2) 113-120 [2014]

Statistical analysis

Ex vivo studies were conducted for prepared gels and were

compared with control. Release profile is shown in figure 4.
Cumulative drug permeated was found to be 52.82.32,
42.322.52g/cm2for CHL1G, CHL2G but with control it was just
7.981.86g/cm2. Steady state transdermal flux was found to be
2.210.27, 1.770.08g/cm2/hr for CHL1G, CHL2G respectively
and 0.280.03 g/cm2/hr for control. Permeability coefficient was
3.530.08X10-3, 2.840.04X10-3 for CHL1G, CHL2G and
0.450.02X10-3 cm/hr. Enhancement ratio was found to be 7.78,
6.25 times for CHL1G,CHL2G. Lag time decreased from 4.20.2
for control to 2.50.11, 20.05 hrs for CHL1G, CHL2G
respectively. Drug permeation, flux, enhancement ratio and lag
time was observed to be high for gel preparation with CHL1G

The results obtained were analyzed statistically using one way

ANOVA (Tukeys multiple comparison test) and is depicted in (table
3).Results of control and CHL1 were significant (p<0.001) in SSTF,
Q24, permeability coefficient, enhancement ratio and lag time,
CHL1 and CHL2 were significant (p<0.001) in permeability
coefficient and enhancement ratio but Q24, SSTF and lag time
were not significant (p>0.05). CHL1 and CHF2 were significant
(p<0.01) in permeability and enhancement, Q24 and SSTF but lag
time was not significant (p.0.05). Comparing CHL2 with control
showed significance of p<0.001 for SSTF, Q24, permeability
coefficient, enhancement ratio, lag time. CHL2 and CHF2 are
significant in permeability, enhancement (p<0.001), Q24 and SSTF
were not significant. Comparing CHF2 with control Q24,
permeability coefficient, enhancement ratio showed significance of
p<0.01, SSTF with significance of P<0.005 and significance of
p<0.01 in lag time.
SSTF, Q24, permeability coefficient, enhancement ratio and lag
time were observed to be significant to p<0.001 in CHL1G and
CHL2G with control but lag time was not significant in CHL2G.
SSTF, Q24, permeability coefficient, enhancement ratio were
significant but lag time was not significant (p>0.05) when
comparing CHL1G, CHL2G.
From this analysis it is observed that terpenes shows significant
effect on permeability coefficient and flux was influenced by
permeability enhancer. Least lag time was observed with CHL2G

60
40

CHL1
CHL2

20

CNT

0
0

10

Time(hrs)

20

30

Figure 4: Ex vivo permeation studies

Table 3: Statistical analysis by ANOVA (Tukeys multiple comparison test)

CNT vs CHL1

Cumulative amount
permeated (Q24)
***

CNT vs CHL2

***

Permeability
coefficient
***

Enhancement
ratio
***

***

***

***

***

***

***

CNT vs CHF2

***

***

***

**

F value

61.26

17.88

9640

18610

23.94

CHL1 vs CHL2

NS

NS

***

***

NS

CHL1 vs CHF2

**

***

***

NS

CHL2 vs CHF2

NS

NS

***

***

NS

F Value

61.26

17.88

9640

18610

23.94

CNT vs CHL1G

***

***

***

***

NS

CNT vs CHL2G

***

***

***

***

CHL1G vs CHL2G

***

***

***

***

NS

3.565e+006

5.922

SSTF

Gel

Invasomes

Control vs Other
formulations

Parameters

Comparision with in formulations

Cummulativeamount
permeated(g/cm2)

Ex vivo studies of gel

F value
1.031e+006
191731
488463
n = 2; *** (p<0.001); ** (p<0.01); * (p<0.005); NS non significant (p>0.05)

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Lag time

Lakshmi et al. International Journal of Drug Delivery 6 (2) 113-120 [2014]

CHL1

Table 4: release kinetics of prepared invasomes and gel.

Zero order
First order
Higuchi
Peppas
r2
r2
r2
r2
n
0.990
0.9068
0.952
0.982
0.434

Fickian diffusion

CHL2

0.996

0.7341

0.936

0.923

0.471

Fickian diffusion

CHF2

0.995

0.8202

0.939

0.969

0.472

Fickian diffusion

CHL1G
0.992
0.9078
0.962
CHL2G
0.986
0.7641
0.926
Release kinetics of optimized 0 order kinetics, fickian n<0.5

0.982
0.943

0.454
0.431

Fickian diffusion
Fickian diffusion

Ge
Invasomes
l

Formulations

Release mechanism

Release kinetics

Conclusion

Release kinetics was observed by fitting the data in to Zero order,

First order, Higuchis, Korsemeyer peppas equations and was
found to follow zero order release with Fickian diffusion
mechanism.Table-4
Skin irritation studies were performed on depilated rabbit and was
assessed and scored according to primary dermal irritation index
classification. Gel formulation CHL1G was applied on to depilated
skin and was confirmed that there was no sign of erythema or
edema.

Because of its poor solubility, its instability in alkaline pH curcumin

is formulated as transdermal formulation. Curcumin was
complexed with CD and HPCD. Improved solubility and stability
was observed with HPCD prepared by co-precipitation method
than physical mixture method. Optimized complex ie., 1:2
proportion complex is incorporated into invasomes with limonene,
fenchone, nerolidol as terpenes which acted as phospholipid
membrane flexibilizers, penetration enhancers. 1% soya
phosphotidylcholine, 0.5% limonene was optimized which showed
Q24 of 70.32 g/cm2, SSTF of 3.34 g/cm2/hr-1, permeability
coefficient of 5.35 cm/hr, and decreased lag time of 1 hr.
formulation CHL1 was found to be better in all characteristics and
was incorporated into 2% HPMC K4M gel formulation. Further in
vivo studies are to be carried out to assess the pharmacokinetics of
curcumin invasomal formulations.

Stability studies
Stability studies of optimized formulation was carried out by sealing
the formulation in 10 ml glass vial and refrigerated at 4 - 8C and at
room temperature for 1 month. Drug content was determined and
there was a decrease of only 10 % of entrapped drug after 1 month
when stored at refrigeration. But when stored at room temperature
the loss was upto 50%. Hence curcumin loaded invasomes are
stored at 4 - 8C as aggravated temperatures causes leaking by
transition of lipid bilayer or chemical degradation of lipids.

Abbreviations
HPMC- Hydroxy propyl methyl cellulose

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