You are on page 1of 10

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/224899154

Development of span 80–tween 80 based fluid-filled organogels as a matrix for


drug delivery

Article  in  Journal of Pharmacy And Bioallied Sciences · April 2012


DOI: 10.4103/0975-7406.94822 · Source: PubMed

CITATIONS READS
31 1,557

5 authors, including:

Nikhil Kumar Sai Sateesh Sagiri


Indian Institute of Technology Kanpur City College of New York
11 PUBLICATIONS   458 CITATIONS    56 PUBLICATIONS   1,303 CITATIONS   

SEE PROFILE SEE PROFILE

Kunal Pal Sirsendu Sekhar Ray


National Institute of Technology Rourkela National Institute of Technology Rourkela
296 PUBLICATIONS   6,002 CITATIONS    63 PUBLICATIONS   815 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Voice-Controlled Home Automation View project

Electronic devices for rehabilitation engineering View project

All content following this page was uploaded by Kunal Pal on 06 May 2014.

The user has requested enhancement of the downloaded file.


[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

Original Article
Development of span 80–tween 80 based fluid-
filled organogels as a matrix for drug delivery
Charulata Bhattacharya, Nikhil Kumar, Sai S. Sagiri, Kunal Pal, Sirsendu S. Ray

Department of ABSTRACT
Biotechnology and
Background: Organogels are defined as 3-dimensional networked structures which immobilize apolar solvents
Medical Engineering,
National Institute of
within them. These gelled formulations are gaining importance because of their ease of preparation and inherent
Technology, Rourkela, stability with improved shelf life as compared to the ointments. Aim: Development of span 80–tween 80
India mixture based organogels for the first time by fluid-filled fiber mechanism. Materials and Methods: Span 80
and tween 80 were used as surfactant and co-surfactant, respectively. The surfactant mixtures were dissolved
Address for correspondence: in oil followed by the addition of water which led to the formation of organogels at specific compositions.
Dr. Kunal Pal, The formulations were analyzed by microscopy, X-ray diffraction (XRD), time-dependent stability test and
E-mail: pal.kunal@yahoo.
com
accelerated thermal stability test by thermocycling method. Ciprofloxacin, a fourth-generation fluoroquinolone,
was incorporated within the organogels. The antimicrobial activity of the drug loaded organogels and in vitro
drug release from the gels was also determined. Results and Conclusions: Microscopic results indicated that
the gels contained clusters of water-filled spherical structures. XRD study indicated the amorphous nature of
the organogels. The release of the drug was found to be diffusion controlled and showed marked antimicrobial
property. In short, the prepared organogels were found to be stable enough to be used as pharmaceutical
formulation.
Received : 10‑03‑11
Review completed : 07‑06‑11
Accepted : 14‑08‑11 KEY WORDS: Antimicrobial activity and drug release, organogel, span 80, tween 80

O rganogels may be defined as a gelled system in which


the external organic phase has been immobilized by the
3-dimensional network formed by the organogelators. The
includes lecithin organogel where the increase in the viscosity is
approximately 104–106-fold.[8,9] Most organogels are isotropic in
nature and do not allow polarized light to pass through them.[10-12]
formation of the networked structure may be attributed to the The increased applications of organogels as delivery vehicles in
physical or covalent interactions amongst the gelator molecules. cosmetics, nutraceutical and pharmaceutical industries may be
In general, physical gels show gel-to-sol phase transition (Tg).[1-3] attributed to the thermostable nature of the organogels with
This property is not shown by the gels formed due to chemical improved shelf life.[13,14] Depending on the composition of the
reactions. Tg has been determined by various methods including organogels, they may be either transparent or opaque. The
“dropping ball” technique,[4] bubble motion[5] or by the inverted lecithin organogels are transparent in nature while the sorbitan
test tube method.[6] The physical gels show shear thinning monostearate organogels are opaque in nature.[9,15-17] Till recent
behavior and can be best explained by plastic flow behavior.[7] past, most organogels were developed using components which
During the formation of physical organogels, there is an increase were not regarded as biocompatible. Keeping the long-term
in the viscosity as aqueous phase is added to the apolar solution stability and the ability of the organogels to accommodate
of the amphipaths. The classical example of this phenomenon both lyophilic and lyophobic agents in mind, scientists are
working toward the development of organogels with improved
Access this article online
biocompatibility.[17] This has added a new dimension in the food
Quick Response Code:
Website: and pharmaceutical industries because of the easy preparation
www.jpbsonline.org of the organogels.[18] The current study reports the development
and characterization of the span 80–tween 80 mixture based
DOI: organogels. To the best of the knowledge of the authors, the
10.4103/0975-7406.94822 development of the organogels using span 80–tween 80 mixtures
has not been reported till date.

How to cite this article: Bhattacharya C, Kumar N, Sagiri SS, Pal K, Ray SS. Development of span 80-tween 80 based fluid-filled organogels as a matrix for
drug delivery. J Pharm Bioall Sci 2012;4:155-63.

Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2 155 
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

 Bhattacharya, et al.: Span 80-tween 80 based organogels

Materials and Methods Table 1: Composition of the organogels used for stability tests
Organogel Surfactant % Composition
Materials mixture Surfactant Water Oil
G_1 1:1 46 24 30
Span 80 (sorbitan monooleate) was procured from Loba G_2 61.47 18.03 20.49
chemie, Mumbai, India. Tween 80 (polyoxyethylene sorbitan G_3 20 30 50
H_1 1:2 46 24 30
monooleate), rhodamine B and tetracycline hydrochloride were
H_2 61.47 18.03 20.49
procured from Himedia, Mumbai, India. Ciprofloxacin was H_3 20 30 50
obtained from Fluka Biochemika, China, and metronidazole I_1 1:3 46 24 30
was a gift from Aarti Drugs, Mumbai, India. Edible sunflower oil I_2 61.47 18.03 20.49
I_3 20 30 50
was purchased from the local market. Dialysis tubing (molecular
weight cutoff: 50 kDa) was purchased from Himedia, Mumbai,
India. All the experimental samples were prepared using double- Microscopic study
distilled water.
The samples were observed under Hund, Wetzlar Light
Methods microscope (H-600, Germany) coupled with JVC color video
camera (TK-C1381, Japan). H_1 organogel was observed
Organogel preparation under Zeiss confocal microscope (LSM 500, Germany) and
environmental scanning electron microscope (ESEM) (Quanta
Surfactant mixtures of span 80 and tween 80 were prepared 200, FEI Company, The Netherlands).
so as to have span 80:tween 80 ratios of 1:1 (G-organogels),
1:2 (H-organogels) and 1:3 (I-organogels). Specified amounts XRD analysis
of the surfactant mixtures were added to specified volume of
sunflower oil in 15-ml culture bottles kept on magnetic stirrer. X-ray diffraction (XRD) analysis was carried out for G_1, H_1,
The above mixture was stirred for 20 min. Subsequently, water I_1 and H_1 + D (H_1 organogel containing 1% ciprofloxacin)
was added drop by drop to the surfactant–oil solution with the and ciprofloxacin. The test was performed using Cu–Kα source,
use of a burette until the formation of organogel or until the with the machine operating at 30 kV and 20 mA. The samples
total fraction of water has reached 80% of the volume of the were scanned within the range of 10°–50° 2θ at a rate of 2° 2θ
surfactant–oil–water mixture. Based on the composition of the per minute.
surfactant–oil–water mixture, the systems either formed gelled
structures or remained as a liquid mixture. A ternary phase Rheological study
diagram was plotted to find the area of the gelation. Origin 8
(Professional) software was used to plot the ternary plot. Rheological studies of the organogel samples were carried
out using cone and plate viscometer (BOHLIN VISCO-88,
Samples for morphology and microscopic studies were prepared Malvern, UK). The diameter of the cone was 30 mm and had
in a similar manner except the use of 0.01% (w/v) rhodamine B an angle of 5.4°. A gap of 0.15 mm and a temperature of 25°C
solution in water as the aqueous phase. were maintained throughout the experiment. The samples were
subjected to a shear rate sweep starting from 10 to 60 sec−1. The
The samples containing antimicrobial drugs were prepared results were obtained in triplicate.
by using drug (ciprofloxacin, metronidazole or tetracycline)
suspension in oil. The rest of the procedure for the preparation Sol–gel transition study
of the organogels was same. The final composition of the drugs
in the organogel was 1% (w/w). The organogels were heated in a temperature-controlled water
bath (Lauda Ecoline, RE104, Germany). The experiment was
Characterization of organogels started at 30°C and the temperature was increased up to 80°C
with an increment of 5°C. The samples were incubated at the
The compositions of all the prepared organogels by the above specified temperature for 5 min and were observed by inverted
said method are summarized in Table 1. Of these, three samples test tube method. The temperature at which the gel started to
of organogels, one each from G, H and I groups, i.e. G_1, H_1, flow was regarded as gel-to-sol transition. The study was done
I_1, were used for the further characterization of the organogels. in triplicate.

Macroscopic study Accelerated stability testing

The samples prepared with aqueous rhodamine B solution Freshly prepared samples were subjected alternatively to
were visually examined to understand the phenomenon of the temperatures of 50°C and −20°C for a period of 15 min. The
gelation. The photographs of the samples were taken with a 10 experiment was carried out for 8 h. The samples were analyzed
megapixel Canon DSLR camera. visually for any instability.

 156 Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

Bhattacharya, et al.: Span 80-tween 80 based organogels 

Stability studies on a time scale indicates that the samples attain low energy state as they
undergo transition into gelled structures and may be regarded
The freshly prepared samples were kept at the ambient as thermodynamically stable. In general, the developed
temperature (AT), 5°C and 37°C. The samples were visually organogels were white to pale yellow in color depending on
observed at regular intervals of time for any instability. the composition and were opaque in nature. They were having
slight odor and were oily to touch.
In vitro drug release studies
Ternary phase diagrams were prepared for the G, H and I type
Accurately weighed 1 g of the organogel samples (G_1 + D, organogels [Figure 2]. Each arm of the phase diagram represents
H_1 + D, I_1 + D), containing 1% (w/w) ciprofloxacin, were the proportion of a particular component. The formation of the
put into dialysis tubings (molecular weight cutoff: 50 kDa),
organogel was dependent on the concentration of all the three
whose one end was secured by a knot. After filling the samples
components, viz. surfactant mixture, sunflower oil and water.
within the tubing, the other end was also secured by a knot. The
From the experimental results, it can be concluded that the
tubings were dipped into a beaker containing 50 ml of double-
composition of the surfactant mixture played an important role
distilled water, which served as a dissolution medium. Until
the first hour completion, the sample tubings were taken out in governing the phenomenon of gelation as can be visualized
from the beaker and were put into another beaker containing from the area of gelation in the ternary phase diagram. Table 2
fresh 50 ml of water at every 15 min interval. After 1 h, the identifies the % gelled area, given by the formula:
changeover was done at an interval of 30 min. Two milliliters WG
of the dissolution medium containing the drug was collected at % Gelled Area = ×100 (1)
WT
the above-mentioned intervals in a test tube for further studies
and the rest was discarded. The experiment was carried out for where WG = weight of the paper representing the gelled area
a period of 8 h. By using the collected samples, the amount of and WT = weight of the paper representing the total area.
ciprofloxacin released from the organogels into the dissolution
medium was measured at λmax of 237 nm using UV-visible Initially, the % gelation area increased from G to H type
spectrophotometer (Shimadzu UV 1601 r). The experiments organogels. It may be attributed to the increase in the tween
were carried out in triplicates. 80 (water soluble surfactant) fractions, which may result in the
increased water uptake, thereby resulting in the increased gelled
Antimicrobial test phase.[12] With the further increase in the tween 80 fraction
from H to I type organogel, there was a slight decrease in the %
Gram-positive bacterium Bacillus subtilis (MTCC 121) and gelled area. This may be attributed to the further increase in the
gram-negative bacterium Escherichia coli (NCIM 5051) were hydrophilicity with the subsequent alteration in the intergelator
used for antimicrobial study using nutrient agar solid medium hydrophobic bonding.[19]
as the culture medium. Warm, sterilized medium was poured
into the Petri plates and was allowed to solidify. One milliliter
of the cell suspension (containing 10−6 to 10−7 cfu/ml, approx.)
was spread over the surface of the nutrient solid agar medium.
Thereafter, wells of diameter 9 mm were made into the agar
plates using a borer to accommodate 0.5 g of antimicrobial
loaded H_1 organogels. The Petri plates were incubated at 35°C
for 18 h. The zone of inhibition was measured by a ruler. The
H_1 samples of organogels without drug served as control for
the counterpart with drug.

Results and Discussion

Preparation of the organogels

The organogels were prepared by dissolving the surfactant


mixture in sunflower oil followed by the addition of water.
With the initial addition of water, the mixture turned into a Figure 1: Organogel samples of different composition
white turbid solution. As further amount of water was added,
the samples either formed a gelled structure or remained as
turbid solution. The samples were regarded as organogels if Table 2: Percentage gelled area of the organogel groups
the surfactant–sunflower oil–water mixture did not flow when Organogel groups % Gelled area
the culture bottles were inverted [Figure 1]. The samples G 6.9
which formed gelled structures released heat, indicating H 21.9
I 17.5
an exothermic reaction as the gels were developed. This

Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2 157 
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

 Bhattacharya, et al.: Span 80-tween 80 based organogels

a b c
Figure 2: Ternary phase diagrams of the (a) G, (b) H and (c) I organogels

a b c
Figure 3: Morphological observation of (a) G_1, (b) H_1 and (c) I_1 organogels

Macroscopic study focal lengths. Hence, no conclusion could be drawn from the
micrographs. Subsequently, the samples were analyzed under
The macroscopic study was done by using the samples whose confocal and environmental electron scanning microscopes
aqueous phase contained rhodamine B solution. Figure 3 [Figure 5]. The micrographs indicated the presence of
indicates that the aqueous phase constitutes the internal phase, aggregated granular structures which lead to the formation of
indicating that the organogel is a water-in-oil emulsion. From a 3-dimensional network structure.[16] The apolar fluid phase
Figure 3, it seems that the surfactant molecules self-assembled remained entrapped within this gelled network.[17] With the
increase in the concentration of surfactant mixture, there
into spherical shaped structures,[16] which then underwent
was a corresponding increase in the 3-dimensional networked
physical interactions so as to form agglomeration of the self-
structure as visualized under light microscope [Figure 4].[20]
assembled structures resulting in the formation of a networked
structure. The networked structure, so formed, immobilized the
XRD analysis
external oil phase, leading to the formation of the organogel.
The gels were oily to touch which confirmed that the external The XRD profile of the organogels and ciprofloxacin is shown
phase is apolar in nature. in Figure 6. The XRD of ciprofloxacin alone indicated sharp
peaks at 10.4°, 11.2°, 13.5°, 14.5°, 16.5°, 17.8°, 19.2°, 20.8°, 22.2°,
Microscopic study 22.6°, 23.3°, 24.5°, 25.4° and 26.5° 2θ. The presence of sharp
peaks indicates the crystalline nature of ciprofloxacin, which
Light microscopy revealed that G_1, H_1 and I_1 organogels may be attributed to the highly ordered molecular structure.
are having granular structures [Figure 4]. But the main problem The G_1, H_1 and I_1 organogels showed a broad peak at 20°
with the light microscope is that it provides images from all the 2θ (approx.), though the intensity of the peaks and the profile

 158 Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

Bhattacharya, et al.: Span 80-tween 80 based organogels 

indicates that the suspended ciprofloxacin got entrapped within


the networked structure and was not available on the surface
for detection by XRD technique.

The width of the peak at half maximum (FWHM) is dependent


on the crystallinity of the sample, which in turn is dependent
on hydrophobic interactions amongst the gelator molecules
a b responsible for the formation of an ordered structure. For
the determination of the FWHM, the XRD profile data was
smoothened using Savitzky–Golay filter. The smoothening
was done using 50 points of window and polynomial order
of 5. Subsequently, the smoothened curve was normalized
and the width of the curve at 50% normalized intensity was
calculated which gave the FWHM [Figure 7]. The FWHM
for the G_1, H_1, I_1 and H_1 + D was found to be 9.5, 8.28,
9.39 and 10.66, respectively. In general, lower FWHM values
c indicate higher crystallinity and vice versa. This indicates that
there is an initial increase in the crystallinity with a subsequent
Figure 4: Micrographs of (a) G_1, (b) H_1 and (c) I_1 organogels increase in tween 80. But as the proportion of tween 80 is further
without rhodamine B increased, there is a reduction in the hydrophobic interactions,
resulting in a decrease in the intensity of the peak of the I_1
organogel. The FWHM of the H_1 + D organogels was highest
(10.66), supporting the fact that the ciprofloxacin molecules
are present within the networked structures and interact with
the gelator molecules, thereby resulting in the decrease in the
interactions amongst the gelator molecules. This result shows
decrease in the ordered structure of the organogels, and hence
the increased FWHM.

Rheological study of the organogel

a b The viscosity profile of the organogels indicates a decrease in


Figure 5: Micrographs of H_1 organogel as visualized under (a) the viscosity of the organogels with an increase in the shear
confocal microscope and (b) ESEM rate [Figure 8]. The viscosity profile of the organogel showed
an elastic phase followed by a non-elastic phase. The presence
of the elastic phase may be attributed to the elastic nature
of sorbitan ester organogels.[12] In this region, the physical
interactions amongst the gelator molecules are stronger and
the applied shear is not able to dislodge the gelator molecules
involved in the formation of the gelled structures via fluid-
filled microstructures. As the applied shear is increased, the
hydrophobic interactions are not able to keep the fluid-filled
microstructures together. This results in the transition of the
system from the gelled phase to the free-flowing liquid phase,
marked by the disruption of the 3-dimensional networked
structures.[12]

Thermal study
Figure 6: XRD graphs of G_1, H_1, I_1, H_1 + D and ciprofloxacin The organogels were subjected to increasing temperatures
starting from 30°C. An increment of 5°C was made after 5 min
for the diffractogram were considerably different. The presence incubation at the previous temperature. The samples were
of the peaks at the same position indicates that the composition considered to have undergone gel–sol transition when they
of the organogels is same. The H_1 + D organogel also showed started to flow (determined by inverted test tube method).
a broad peak at 20° 2θ. This indicates that either ciprofloxacin The gel-to-sol transition temperatures were found to be
is present as solution in oil or present within the networked at 60°C, 70°C and 65°C for G_1, H_1 and I_1 organogels,
structure of the gelators. It was found experimentally that 1% respectively [Figure 9]. As the temperature is increased, there
(w/v) ciprofloxacin in sunflower oil forms a suspension, which is a corresponding increase in the surface free energy with

Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2 159 
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

 Bhattacharya, et al.: Span 80-tween 80 based organogels

Figure 9: Gel–sol transition temperatures of organogels


Figure 7: Normalized XRD graphs of G_1, H_1, I_1 and H_1 + D
organogels
organogels loaded with ciprofloxacin showed lower transition
temperatures of 55°C, 65°C and 60°C for G_1 + D, H_1 + D
and I_1 + D organogels, respectively [Figure 9]. This may be
attributed to the interaction of the ciprofloxacin molecules
with the gelator molecules, resulting in decreased interaction
amongst the gelator molecules.

Accelerated stability testing

The accelerated stability testing of the G_1, H_1 and I_1


organogels was carried out by the thermocycling method.
The organogels may be considered as water-in-oil emulsion.
Emulsions, in general, are considered as a complex system
whose stability cannot be studied by Arrhenius relationship
which is usually used for stability testing of various simple
pharmaceutical, nutraceutical and cosmetic formulations. The
simplest method of conducting the same is to use a freeze–
thaw method. The method employs continuous exposure of
the samples to a freeze–thaw cycle at short intervals of time.
The freezing temperature should be ≤−5°C, whereas the
thawing temperature is dependent on the type of formulation.
This method only provides a prediction and does not give us
an absolute value. This has been attributed to the process of
destabilization only during freeze–thaw cycles and not under
storage conditions.[21] The testing considers the probable change
in the properties of the surfactants at elevated temperatures,
which in turn may alter the partitioning property of the
Figure 8: Viscosity profile of the organogels surfactant and the probable rupture of the surfactant layer in
the presence of ice crystals at lower temperatures. In either
of the case, the samples will become unstable. In general, it
a subsequent increase in the mobility of the self-assembled
is considered that the samples should withstand at least five
structures formed by the gelators. With further increase in
cycles of freeze–thawing process.[22] The developed organogels
the temperature, the interaction amongst the self-assembled
were able to sustain much more than five cycles, indicating
structures gets abolished, and hence results in the disruption their inherent stability. The observations of the experiment are
of the networked structure, which causes the system to flow tabulated in Table 3.
freely.[16] The results are in conjunction with the XRD results,
which showed highest crystallinity for H_1 followed by I_1 and Stability studies on time scale
G_1. The energy needed for the disruption of a gel is expected
to be higher, so as the samples with higher crystallinity. The The samples of organogels were kept at AT, 5°C and 37°C. The

 160 Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

Bhattacharya, et al.: Span 80-tween 80 based organogels 

composition of the samples used for the stability studies is given i.e. H_1 > I_1 > G_1. The study indicates that if the developed
in Table 1. The observations of the test are reported in Tables 4–6. organogels are stored either in a cold or cool place, they can have
In general, it was found that the samples kept at 5°C were considerably longer shelf life and may be used in formulating
stable for a prolonged period of time. The samples kept at 37°C drug delivery systems.
showed destabilization of the organogels within a period of 1
week, whereas the samples kept at AT showed stability for an In vitro drug release
intermediate period of time. The H_1 organogels were more
stable for prolonged periods of time at AT compared to others. The release rate of drug from organogel systems depends on
This may be attributed to the crystallinity of the sample. The the drug partition coefficient and drug solubility in the oil
stability and % crystallinity of organogels follow the same order, and aqueous phases.[11] Ciprofloxacin as a model drug was
incorporated within organogels and its release rate was studied.
G_1 + D [G_1 organogel containing 1% (w/w) ciprofloxacin]
Table 3: Observations of the accelerated stability test
organogel showed maximum percentage of drug release at
Time (h) Observations
the end of 8 h, followed by the release of the drug from I_1
G_1 H_1 I_1 + D [I_1 organogel with 1% (w/w) ciprofloxacin] and H_1 +
0 Gel Gel Gel D [H_1 organogel with 1% (w/w) ciprofloxacin] organogels
1 Gel Gel Gel
[Figure 10]. With the increase in crystallinity of the organogel,
2 Gel Gel Gel
3 Gel Gel Gel there is a decrease in the release behavior of the drug. As the
4 Phase separation Gel Gel crystallinity of samples increases, there is a corresponding
starts (at 3.5 h) increase in the crystallite regions which act as crosslinked sites,
5 Gel at −20°C Phase separation Gel and hence an increase the crosslinking density. [11] The hindrance
starts (at 5.45 h)
to the diffusion of solutes is higher in matrices with higher
6 Destabilization Gel at −20°C Phase separation
(at 6.10 h) starts (at 6.30 h) crosslinking density. This results in the decrease in the flux of
7 Destabilization Destabilization Gel at −20°C the drug from the organogel. This phenomenon is confirmed
(at 6.50 h) in majority of the reported systems.[23] As per XRD results, the
8 Destabilization Destabilization Destabilization H_1 organogels are more crystalline than the others and these
(7.45 h)
results are in accordance with the in vitro drug release pattern

Table 4: Observations of the stability test for G organogels


Samples Sample conditions
G_1 G_2 G_3
AT 5°C 37°C AT 5°C 37°C AT 5°C 37°C
Observations Day 0 Stable Stable Stable Stable Stable Stable Stable Stable Stable
Day 1 Stable Stable Not stable Stable Stable Not stable Stable Stable Not stable
1 week Stable Stable - Stable Stable - Stable Stable -
1 month Stable Stable - Stable Stable - Stable Stable -
2 months Stable Stable - Stable Stable - Stable Stable -
3 months Stable Stable - Not stable Stable - Stable Stable -
4 months Not stable Stable - - Stable - Stable Stable -
5 months - Stable - - Stable - Not stable Stable -
6 months - Stable - - Stable - Not stable Stable -
AT: Ambient temperature

Table 5: Observations of the stability test for H organogels


Samples Sample conditions
H_1 H_2 H_3
AT 5°C 37°C AT 5°C 37°C AT 5°C 37°C
Observations Day 0 Stable Stable Stable Stable Stable Stable Stable Stable Stable
Day 1 Stable Stable Stable Stable Stable Not stable Stable Stable Not stable
1 week Stable Stable Not stable Stable Stable - Stable Stable -
1 month Stable Stable - Stable Stable - Stable Stable -
2 months Stable Stable - Stable Stable - Stable Stable -
3 months Stable Stable - Stable Stable - Stable Stable -
4 months Stable Stable - Stable Stable - Stable Stable -
5 months Stable Stable - Stable Stable - Stable Stable -
6 months Stable Stable - Stable Stable - Not stable Stable -
7 months Stable Stable - Not stable Stable - - Stable -
8 months (+) Not stable Stable - - Stable - - Stable -
AT: Ambient temperature

Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2 161 
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

 Bhattacharya, et al.: Span 80-tween 80 based organogels

Table 6: Observations of the stability test for I organogels


Samples Sample conditions
I_1 I_2 I_3
AT 5°C 37°C AT 5°C 37°C AT 5°C 37°C
Observations Day 0 Stable Stable Stable Stable Stable Stable Stable Stable Stable
Day 1 Stable Stable Not stable Stable Stable Not stable Stable Stable Not stable
1 week Stable Stable - Stable Stable - Stable Stable -
1 month Stable Stable - Stable Stable - Stable Stable -
2 months Stable Stable - Stable Stable - Stable Stable -
3 months Stable Stable - Not stable Stable - Stable Stable -
4 months Stable Stable - - Stable - Stable Stable -
5 months Stable Stable - - Stable - Stable Stable -
6 months Not stable Stable - - Stable - Stable Stable -
AT: Ambient temperature

Table 7: Antimicrobial test results


Bioactive agent Zone of inhibition (diameter, cm)
E. coli Bacillus subtilis Control
Ciprofloxacin (1%) 4.0 ± 0.3 4.5 ± 0.1 Nil
Metronidazole (1%) 2.5 ± 0.1 - Nil
Tetracycline HCl (1%) 2.2 ± 0.2 4.0 ± 0.2 Nil

80–tween 80 mixture based organogels for the first time. The


gels were developed by fluid-filled mechanism. The developed
organogels were found to be stable in nature and were able
to sustain heat shocks for prolonged period. The drug release
study from the organogels indicated diffusion-dependent
release. Since the organogels were prepared using FDA approved
components, the organogels are expected to be biocompatible.
Based on the preliminary studies, it seems that the span 80–
tween 80 mixture based organogels may be tried as a drug carrier
for transdermal bioactive agent delivery.
Figure 10: In vitro drug release data for ciprofloxacin
Acknowledgments
of the gels. The % cumulative release of the drug from H_1 +
The authors acknowledge the funding received from National Institute
D organogels is about 5% compared to I_1 + D’s 12% and G_1
of Technology, Rourkela, India, during the completion of the work.
+ D’s 18% of the total drug incorporated. The G_1 organogels
Authors also express their thanks to Prof. G. R. Satpathy, Prof. B. P.
are less crystalline, so they have released the drug in higher
Nayak and Prof. S. Paria for giving access to their laboratory during
concentrations in vitro. The order of % cumulative drug release
the study.
is G_1 + D > I_1 + D > H_1 + D.

Antimicrobial studies
References
1. Guenet JM. Polymer thermoreversible gels vs organogels. Macromol
The bioactive agents having antimicrobial properties were Symp 2006;241:45-50.
incorporated within the organogels. A bore of 9 mm diameter 2. Díaz DD, Marrero TJ, Velázquez D1, Ravelo ÁG. Polymer
thermoreversible gels from organogelators enabled by click
was made in the nutrient agar plates containing the specific chemistry. Tetrahedron Lett 2008;49:1340-3.
microorganism. Table 7 shows the results of the test. It was 3. Dasgupta D, Srinivasan S, Rochas C, Ajayaghosh A, Guenet JM.
found that the bioactive agents were able to diffuse out of the Hybrid thermoreversible gels from covalent polymers and organogels.
Langmuir 2009;25:8593-8.
organogels and showed their antimicrobial property for a period
4. Tan H, Moet A, Hiltner A, Baer E. Thermoreversible gelation of atactic
of 18 h. On the other hand, control organogel samples did not polystyrene solutions. Macromolecules 1983;16:28-34.
show any zone of inhibition. This indicates that the organogels 5. Stein SB, Angew HZ. Math Mech 2000;80:827-34.
may be used as a controlled delivery system, where they can 6. Macosko CW. Rheology: Principles, Measurements and Applications.
NewYork: VCH Publishers; 1994.
deliver the bioactive agents for a prolonged period of time. 7. Abdallah DJ, Sirchio SA, Weiss RG. Hexatriacontane Organogels.
The first determination of the conformation and molecular packing
of a low-molecular-mass organogelator in its gelled state. Langmuir
Conclusion 2000;16:7558-61.
8. Shchipunov YA. Lecithin organogels: Rheological properties of
This study reports the successful development of novel span polymer-like micelles formed in the presence of water. Colloid J

 162 Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2
[Downloaded free from http://www.jpbsonline.org on Saturday, May 05, 2012, IP: 203.124.151.34]  ||  Click here to download free Android application for this journal

Bhattacharya, et al.: Span 80-tween 80 based organogels 

1995;57:556-60. 1988;92:829-33.
9. Kumar R, Katare OP. Lecithin organogels as a potential phospholipid- 16. Murdan S, Gregoriadis G, Florence AT. Novel sorbitan monostearate
structured system for topical drug delivery: A review. AAPS organogels. J Pharm Sci 1999;88:608-14.
PharmSciTech 2005;6:E298-310. 17. Murdan S. Organogels in drug delivery. Expert Opin Drug Deliv
10. Kantaria S, Rees GD, Lawrence MJ. Gelatin-stabilised microemulsion- 2005;2:489-505.
based organogels: Rheology and application in iontophoretic 18. Vintiloiu A, Leroux JC. Organogels and their use in drug delivery -- A
transdermal drug delivery. J Control Release 1999;60:355-65. review. J Control Release 2008;125:179-92.
11. Nasseri AA, Aboofazeli R, Zia H, Needham TE. Lecithin–stabilized 19. Zhu G, Dordick JS. Solvent effect on organogel formation by low
microemulsion–based organogels for topical application of molecular weight molecules. Chem Mater 2006;18:5988-95.
20. Jibry N, Heenan RK, Murdan S. Amphiphilogels for drug delivery:
ketorolac tromethamine. II. In vitro release study. Iran J Pharm Res
Formulation and characterization. Pharm Res 2004;21:1852-61.
2003;117:123.
21. Lieberman AH, Riege MM, Banker SG. Pharmaceutical dosage forms:
12. Upadhyay KK, Tiwari C, Khopade AJ, Bohidar HB, Jain SK. Sorbitan
Disperse systems. Google books 1996;2:93.
ester organogels for transdermal delivery of sumatriptan. Drug Dev
22. Gooch WJ. Emulsification and polymerization of alkyd resins. Kluwer
Ind Pharm 2007;33:617-25. Academic 2002. p. 52.
13. Avramiotis S, Papadimitriou V, Hatzara E, Bekiari V, Lianos P, Xenakis 23. Pisal S, Shelke V, Mahadik K, Kadam S. Effect of organogel
A. Lecithin organogels used as bioactive compounds carriers. A components on in vitro nasal delivery of propranolol hydrochloride.
microdomain properties investigation. Langmuir 2007;23:4438-47. AAPS PharmSciTech 2004;5:e63.
14. Chen Z, Li F, Yang H, Yi T, Huang C. A Thermostable and long-term-
stable ionic-liquid-based gel electrolyte for efficient dye-sensitized
Source of Support: National Institute of Technology, Rourkela, India,
solar cells. Chem Phys Chem 2007;8:1293-7. Conflict of Interest: None declared.
15. Scartazzini R, Luisi PL. Organogels from lecithins. J Phys Chem

FORM IV
Statement about ownership and other particulars about newspaper (Journal of Pharmacy and Bioallied Sciences) to be published in
the first issue every year after the last day of February as per Rule 8 of the PRB Act
1. Place of publication : Mumbai
2. Periodicity of its publication : Quarterly (January, April, July and October)
3. Printer’s Name : Hemant Manjrekar
Nationality : Indian
(a) Whether a citizen of India? : Yes
(b) If a foreigner, the country of origin : N.A.
Address : B5-12, Kanara Business Center,
Off Link Rd, Ghatkopar (E),
Mumbai - 400075, India

4. Publisher’s Name : Hemant Manjrekar


Nationality : Indian
(a) Whether a citizen of India? : Yes
(b) If a foreigner, the country of origin : N.A.
Address : B5-12, Kanara Business Center,
Off Link Rd, Ghatkopar (E),
Mumbai - 400075, India
Phone: 91-22-6649 1818/1816

5. Editor’s Name : Dr. Himanshu Gupta


Nationality : Indian
(a) Whether a citizen of India? : Yes
(b) If a foreigner, the country of origin : N.A.
Address : 21, Jaina Building, Roshanara Road
Delhi-110007, India

6. Names and addresses of individuals who own : Organization of Pharmaceutical Unity with BioAllied Sciences (OPUBS)
the newspaper and partners or shareholders
holding More than one per cent of the total capital.

I, Dr. Himanshu Gupta hereby declare that the particulars given above are true to the best of my knowledge and belief.

Date: 1st March 2012 Hemant Manjrekar Dr. Himanshu Gupta

Journal of Pharmacy and Bioallied Sciences April-June 2012 Vol 4 Issue 2 163 

View publication stats

You might also like