Jurnal Mikroemulsi PDF

International Journal of Drug Development & Research
| October-December 2011 | Vol. 3 | Issue 4 | ISSN 0975-9344 |

Available online http://www.ijddr.in
Covered in Official Product of Elsevier, The Netherlands
2010 IJDDR
Formulation Development & Characterization of Microemulsion
Drug delivery systems Containing Antiulcer drug
Sajal Kumar Jha1, Roopa Karki2, Venkatesh D.P2, Geethalakshami A3
1
Department of Pharmaceutics, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal.
2
Department of Pharmaceutics, Acharya & B.M Reddy College of Pharmacy, Bangalore, Karnataka.
3
Department of Pharmaceutics, Oxford College of Pharmacy, Bangalore, Karnataka.
FULL Length Research Paper

Covered in Index Copernicus with IC Value 4.68 for 2010
Abstract
Key words:
An attempt was made to develop an oral
Microemulsion; Famotidine; BCS Class III drugs;
microemulsion formulation for enhancing the
Surfactant; Cosurfactant.
bioavailability of famotidine is a BCS class III

drugs which are known to have high solubility but
How to Cite this Paper:
low
Sajal Kumar Jha, Roopa Karki, Venkatesh
permeability.
An
Olive
oil
based
microemulsion formulation with Tween 80 as
D.P,
Geethalakshami.
Formulation
surfactant and PEG 400 as cosurfactant was
Development & Characterization of Microemulsion
developed for oral delivery of famotidine. A single
Drug delivery systems Containing Antiulcer drug,
isotropic region, which was considered to be a
Int. J. Drug Dev. & Res., Oct-Dec 2011, 3(4): 336-343
bicontinuous microemulsion, was found in the

at
Copyright 2010 IJDDR, Sajal Kumar Jha et
various Tween80: PEG 400: oil ratios. The
al. This is an open access paper distributed under the
microemulsion system was also investigated in
copyright agreement with Serials Publication, which
terms of other characteristics, such as viscosity,
permits
pH, conductivity, clarity, particle size, in vitro drug
reproduction in any medium, provided the original
release, in vitro intestinal permeability study
work is properly cited.
pseudoternary
phase
diagrams
developed
unrestricted
use,
distribution,
and
compared to the plain drug solution (64.18%). The

developed microemulsion system improved the
permeability
(93.43%)
by
increasing
the
lipophillicity due to the oil phase and also by

destabilizing the membrane stability due the
surfactants and may be used as an enhanced
delivery of BCS class III drugs.
Article History:-----------------------Date of Submission: 08-11-2011

Date of Acceptance: 22-11-2011
Conflict of Interest: NIL
Source of Support: NONE
Introduction:
Microemulsion
*Corresponding author, Mailing address:

Mr. Sajal Kumar Jha
Bengal College of Pharmaceutical Sciences &
Research, Durgapur, West Bengal.
Email: sajal.kumar.jha@gmail.com.
are
clear,
transparent,
thermodynamically stable dispersions of oil and

water, stabilized by an interfacial film of surfactant
frequently in combination with a co-surfactant and
having diameter of the droplets in the range of 100-
Int. J. Drug Dev. & Res., Oct-Dec 2011, 3 (4): 336-343

Covered in Scopus & Embase, Elsevier
336
Sajal Kumar Jha et al: Formulation Development & Characterization of Microemulsion

2000A (10-200 nm). Recently, there has been a
Materials & Methods:
considerable
microemulsion
Famotidine was a generous gift from Microlabs
formulation, for the delivery of hydrophilic as well as
(Bangalore, India);PG, PEG 400, Tween 80, Span 80
lipophilic drug as drug carriers because of its
were obtained from Merc Chemicals (Mumbai,
improved drug solubilization capacity, long shelf life,
India). All other chemicals & sovents used were of
ease
analytical grade.
of
interest
preparation
for
the
and
improvement
of

bioavailability [1]. A microemulsion generally consists
Selection of Oil, surfactants & cosurfactants
of four different components, a lipophilic phase, a
for microemulsion:
[2].
The solubility of famotidine in various oils (Olive oil,
The nature of the components like the oil, surfactant,
groundnut oil, coconut oil & castor oil), surfactants
co-surfactant and water, as well as temperature and
(Tween
pressure which affect the microemulsion systems are
cosurfactants(PG,PEG 400). Was determined by
known as the formulation variables. The quantities of
dissolving an excess amount of famotidine in 2 mL
different substances present, are also likely to change
of each of the selected oils, surfactants, and co-
the properties, and are referred to as composition
surfactants in 5 mL capacity stoppered vials
variables which can be expressed as weight,
separately to determination of solubility. An excess
percentage
or
proportion.
amount of famotidine was added to each 5 mL
applications
of
microemulsions
hydrophilic phase, surfactant and co-surfactant
Pharmaceutical
20,40,60,80
&
Span
80),
drug
capacity stoppered vial and mixed using a vortex
synthesis, purification and extraction as well as drug
mixer. The mixture vials were then kept in a shaker
delivery vehicles and controlled drug release systems.
for 72 h to get to equilibrium. The equilibrated
The biopharmaceutics classification system classifies
samples were removed from the shaker and
drug according to their solubility and permeability
centrifuged at 3000 rpm for 30 min. The supernatant
which is chosen as reference standard are categorized
was taken and filtered through a 0.45 m membrane
as permeable drugs and those drugs which have dose
filter.
number of 1 are classified as soluble. For a BCS
determined
class III drug we need to increase its permeability to
cosurfactants by UV spectrophotometer at their
improve its oral bioavailability because here, in class
respective wavelength 265nm[3].
III drugs they have high solubility but low
Construction
permeability. The purpose of this work was to
diagram:
improve the oral bioavailability of famotidine by
Pseudo ternary phase diagram was constructed
preparation the microemulsion. Since most of the
keeping the ratio of Smix (Tween 80 and PEG 400)
drugs
drug
constant and varying the remaining two components
discovery study to increase their solubility and
(water and oil). For convenience, the phase diagram
efficiency penetrate the biological barriers and reach
was constructed by drawing water dilution lines
their target receptors easily. While increase in the
representing increasing water content and decreasing
lipophillicity helps in better absorption. On the other
surfactant and cosurfactant levels. Four different
hand, some drugs have good water solubility but lack
combinations of oil and Smix (1:9, 2:8, 3:7, 4:6)
sufficient lipophillicity to effectively penetrate the
respectively were made for the study to delineate the
lipoidal tissues and absorption becomes rate limiting
boundaries of phases precisely formed in the phase
are
for such
structurally
candidates [8].
optimized
include
during
The
concentration
in
each
of
of
oils,
famotidine
was
surfactants,
and
Pseudoternary
phase
diagrams. Water was added drop by drop while

mixing on a magnetic stirrer (Remi Instruments Ltd.
337


Mumbai, India) at room temperature & the samples
The pH of the each formulation was found before and
were marked as being optically clear or turbid. The
after diluted to 10 times as well as 25 times be
microemulsion regions were identified as transparent
measured by a pH meter[5].
& isotropic mixtures[4].

Preparation of microemulsion
Conductivity:
On the basis of the solubility studies, oleic acid was
All formulation were studies the effect of the amount
selected as the oil phase. Tween 80 and PEG 400
of water phase of microemulsions was found before
were
and after diluted to 10 times as well as 25 times was
selected
as
surfactant
and
cosurfactant,
respectively. Distilled water was used as an aqueous
monitored
phase. Surfactant and cosurfactant (Smix) were
conductivity[5].
by
measuring
the
electrical
mixed at different mass ratios (1:1,2:1,3:1,4:1). These

ratios were chosen in increasing concentration of
Viscosity:
surfactant
and
The viscosity of all formulations was determined
increasing concentration of cosurfactant with respect
without dilution using normal force measurements
to surfactant for a detailed study of the phase
on the AR 1000-N- Rheometer[6].
with
respect
to
cosurfactant
diagrams. Predetermined amounts of the drug were

dissolved in the required quantity of oil. Surfactant
Particle size measurement:
and co-surfactant were added to the above mixture as
Morphology and structure of the microemulsion were
a fixed ratio. Distilled water was added gradually
studied using transmission electron microscopy
with continuous stirring, which resulted in the
(TEM), A JEOL JEM 100. CX2 is instruments and
formulation of a transparent and homogenous
capable of point to point resolution. To perform the
microemulsion.
the
TEM observations, first take 2 L of formulation (F4)
preparation of microemulsion were the type and
and put it on formvar coated grid, wait for 2 min, add
concentration of the oil phase, surfactant and co-
2L of uranyl acetate and dry it for 1h. After 1 h take
surfactant [4].
the grid and look for the image [4].
Characterization of microemulsion
In vitro drug release study:
Thermodynamic stability studies:
The release of famotidine crude drug powder and
To overcome the problem of metastable formulation,
microemulsion was compared. Release of drugs from
thermodynamic stability tests were performed.
microemulsion employed a dialysis bag/dialysis
Selected formulations were centrifuged at 3000 rpm
membrane with molecular weight. It was first
for 30 min. Those formulations that did not show any
activated using 5% EDTA solution and release
phase separation were taken for the heating and
medium. Phosphate buffer of pH 4.5 has been used
cooling cycle at temperature of 4C and 45C for 48 h
as release medium; the dialysis membrane was
were done. The formulations were then observed for
suspended with the help of glass rod in a beaker
phase separation. The formulations which were
containing 200 mL of phosphate buffer solution
stable at these temperatures, those formulations that
which was kept on magnetic stirrer. The over all
survived thermodynamic stability tests were selected
experiments necessary maintain the temperature of
for the further studies[3].
37C was maintained, the formulation of 5 mL was
Parameters
optimized
for
transferred to a dialysis bag. The sample of 1mL has

pH determination:
been removed from the beaker containing phosphate

338

buffer at definite time intervals 5, 15, 30, 45, 60, 120,
other
formulation,
up to 180 min. and diluted to 10 mL with phosphate
significant. The drug release after 3 h for all
buffer solution. The absorbance of each sample was
formulations varied from 62.45% to 74.25% as
noted at 265 nm[7].
compared
with
and
55.21%
this
for
difference
pure
was
drug.
The
formulation F4 shows highest intestinal permeation

Results & Discussion:
93.43% was found to be significantly higher as
The solubility of famotidine in different oils was
compared with that of plain famotidine is 64.18% &
determined. Among the oils, the solubility of
hence bioavailability. It could be suggested that the
famotidine was found to be highest in Olive oil 6.9%,
microemulsion formulation resulted in spontaneous
lowest solubility in Castor oil 0.95%. Thus, Olive oil
formation of a microemulsion with a small droplet
was selected as the oil phase for the development of
size, which permitted a faster rate of drug release
the formulation. The solubility of famotidine in
into the aqueous phase, much faster than that of
different surfactants was determined. Among the
plain famotidine. Thus, this greater availability of
surfactants, the solubility of famotidine was found to
dissolved
be highest in Tween 80 8.85%, lowest solubility in
formulation could lead to higher absorption and
Tween 20 2.35%.The solubility of famotidine in
higher oral bioavailability.
famotidine
from
the
microemulsion
different cosurfactants was determined. Among the

cosurfactants, the solubility of famotidine was found
Table 1: Solubility of Famotidine in various oils and

surfactants (meanS.D., n=3)
to be highest in PEG 400 is 14.7%, lowest solubility in

PG is 7.12%. The phase study revealed that the
maximum proportion of oil was incorporated in
microemulsion systems when the surfactant to
cosurfactant Smix was 4:1 ratio. From a formulation
viewpoint,
the
increased
oil
content
in
microemulsion may provide a greater opportunity for

the solubilization of famotidine. Pseudoternary phase
Excipients
Volume
(ml)
Quantity
(mg)
Water
100
Solubility
SD
(mg/ml)
00
100
6.90.282
100
5.520.298
Olive oil
Ground nut
oil
Coconut oil
100
1.920.340
Castor oil
100
0.950.238
Serial
No
Tween 80
100
8.850.264
diagram were constructed separately for Smix ratio
Tween 60
100
4.120.359
so O/W microemulsion regions could be identified
Tween 40
100
3.470.287
and microemulsion formulations could be optimized.
Tween 20
100
2.350.191
To
10
Span 80
100
4.950.173
11
PEG 400
100
14.70.416
12
PG
100
7.120.286
overcome
this
metastable
formation,
thermodynamic stability tests were performed. The

formulations
selected
were
centrifugation
and
heating cooling cycle tests, if the microemulsion are

stable over these conditions. The pH of the designed
formulation varied from 7.26 to 7.48 . This was ideal
Table 2: Final formulation with different oil

concentration
Formulation
Code
F1
Oil
(%)
5
S mix
(%)
45
Water
(%)
50
having conductivity between 78.3 to 88.5 s. All four
F2
5.52
44.48
50
formulations had clear transparent yellowish to pale
F3
6.25
43.75
50
yellow
F4
7.12
42.84
50
and near blood pH (7.4). The formulations were
colour.
The
viscosity
of
the
selected
formulations was determined. The viscosity of

formulation F4 (08.21) was lower than that of any
339


Table 3: Physicochemical Parameters of developed Microemulsion

Formulation Code Conductivity
pH
Viscosity
% Transmittance
F1
78.3
7.26
18.64
85.4
F2
86.5
7.63
15.35
89.6
F3
84.7
7.34
12.72
92.5
F4
88.5
7.48
08.21
97.6

Table 4: In vitro drug release studies profile of famotidine from 4 different microemulsion formulations
Formulation
Code
F1
5min
15min
30min
45min
60min
120min
180min
5.122.8
8.36 1.9
17.483.48
30.21 2.31
35.381.56
46.58 2.72
62.45 1.76
F2
4.180.56
7.29 3.46
13.82 2.17
22.64 2.78
32.422.36
40.683.48
59.27 2.18
F3
6.482.04
12.89 2.63
18.32 2.82
24.262.54
34.81 2.60
42.491.92
61.38 1.72
F4
9.152.09
14.56 2.57
22.681.8
27.323.42
33.73 2.17
57.16 2.84
74.25 1.28
(Mean result (g/mL) S.D; (n=3)

Table 5: In vitro intestinal permeability studies profile of famotidine from 4 Different microemulsion
formulations
Formulation
Code
F1
5min
15min
30min
45min
60min
120min
180min
12.23 2.41
23.432.22
48.542.10
54.311.65
75.521.48
82.342.65
86.652.48
F2
16.542.63
27.323.26
51.421.85
56.561.68
78.482.21
84.682.08
88.761.8
F3
21.322.57
32.54 2.81
56.652.64
60.123.23
84.282.34
87.561.90
90.482.18
F4
26.45 1.96
34.321.92
59.352.39
64.412.10
85.531.85
90.651.76
93.433.12
(Mean result (g/mL) S.D; (n=3).

Table 6: In vitro stomach and intestinal permeability studies for pure drug (PD)
Time in min
% Cumulative drug release in intestine
17.59 1.018
15
24.97 2.51
30
35.32 0.79
45
44.26 1.82
60
51.77 2.27
120
60.98 1.72
180
64.18 1.48

340


Figure 1: Pseudoternary phase diagram of system
Figure 2: Transmission electron microscopic positive image of famotidine microemulsion

Formulation (F 4) showing size of some oil droplets with a range of 10-200 nm.
Figure 3: Solubility studies of Famotidine in various components.
341



Figure 4: In vitro drug release studies profile of famotidine from four different microemulsion
formulations.
Figure 5: Comparison of % intestinal drug permeation for F4 & Pure drug

3)
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evaluation of SMEDDS (Self microemulsifying drug
drug delivery system, Current drug delivery., 2006,
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J.,2007; 9(3):E344-E352.
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Patel AR, Vavia PR., Preparation and in vivo
Scriven L.E., Equilibrium bicontinuous structures,

Nature (London)., 1976, 263.
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Shakeel F, Baboota S, Ahuja A, Ali j, Aqil M, Shafiq

S. Nanoemulsion as vehicles for transdermal

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PharmSciTech.,
2007,8(4),104.
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Kantarci G, Ozguney I, Karasulu HY, Arzik S,

Guneri
T.
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ofdifferent
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sodium:preparation, characterization, release rate,

and
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PharmSciTech.,2007,8(4),91.
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Biruss B, Valenta C. The advantage of polymer

addition to a non- ionic oil in water microemulsion
for the dermal delivey of progesterone. Int J
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silymarin by self microemulsifying drug delivery
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343


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International Journal of Drug Development & Research

| October-December 2011 | Vol. 3 | Issue 4 | ISSN 0975-9344 |

FULL Length Research Paper

An attempt was made to develop an oral

Microemulsion; Famotidine; BCS Class III drugs;

microemulsion formulation for enhancing the

bioavailability of famotidine is a BCS class III

How to Cite this Paper:

Sajal Kumar Jha, Roopa Karki, Venkatesh

microemulsion formulation with Tween 80 as

surfactant and PEG 400 as cosurfactant was

Development & Characterization of Microemulsion

developed for oral delivery of famotidine. A single

Drug delivery systems Containing Antiulcer drug,

isotropic region, which was considered to be a

Int. J. Drug Dev. & Res., Oct-Dec 2011, 3(4): 336-343

bicontinuous microemulsion, was found in the

Copyright 2010 IJDDR, Sajal Kumar Jha et

various Tween80: PEG 400: oil ratios. The

al. This is an open access paper distributed under the

microemulsion system was also investigated in

copyright agreement with Serials Publication, which

terms of other characteristics, such as viscosity,

pH, conductivity, clarity, particle size, in vitro drug

reproduction in any medium, provided the original

release, in vitro intestinal permeability study

work is properly cited.

compared to the plain drug solution (64.18%). The

lipophillicity due to the oil phase and also by

Article History:-----------------------Date of Submission: 08-11-2011

*Corresponding author, Mailing address:

thermodynamically stable dispersions of oil and

Int. J. Drug Dev. & Res., Oct-Dec 2011, 3 (4): 336-343

Sajal Kumar Jha et al: Formulation Development & Characterization of Microemulsion

2000A (10-200 nm). Recently, there has been a

Materials & Methods:

Famotidine was a generous gift from Microlabs

formulation, for the delivery of hydrophilic as well as

(Bangalore, India);PG, PEG 400, Tween 80, Span 80

lipophilic drug as drug carriers because of its

were obtained from Merc Chemicals (Mumbai,

improved drug solubilization capacity, long shelf life,

India). All other chemicals & sovents used were of

FULL Length Research Paper

bioavailability [1]. A microemulsion generally consists

Selection of Oil, surfactants & cosurfactants

of four different components, a lipophilic phase, a

The solubility of famotidine in various oils (Olive oil,

The nature of the components like the oil, surfactant,

groundnut oil, coconut oil & castor oil), surfactants

co-surfactant and water, as well as temperature and

pressure which affect the microemulsion systems are

cosurfactants(PG,PEG 400). Was determined by

known as the formulation variables. The quantities of

dissolving an excess amount of famotidine in 2 mL

different substances present, are also likely to change

of each of the selected oils, surfactants, and co-

the properties, and are referred to as composition

surfactants in 5 mL capacity stoppered vials