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Research Paper
Microemulsion Drug Delivery System: A Platform for
Improving Dissolution Rate of Poorly Water Soluble Drug
Surjyanarayan Mandal* and Snigdha. S. Mandal
Baroda College of Pharmacy, Vadodara, India.
ABSTACT:
The aim of the present study was to design novel o/w microemulsion of Glimepiride and to study its
dissolution behavior by raising its solubility. Oil and surfactant were selected based on their drug solubilizing capacity and
HLB value. Pseudoternary phase diagrams were developed at different ratios of Cremophor RH 40 and Transcutol P to
know the microemulsion existing zone. Glimepiride loaded microemulsion using Labrafil M 1944 CS, Cremophor RH 40,
Transcutol P as oil, surfactant and cosurfactant respectively, was prepared and characterized. Accelerated stability study of
the developed microemulsion was carried out for 6 months. Drug solubilization capacity of the microemulsion system was
determined. Solubility of Glimepiride by the O/W microemulsion was increased by 5785 times to that of water
(0.019mg0.002). In-vitro drug diffusion study revealed that after 10 hrs of diffusion, more than 18% of the drug was
diffused from the microemulsion system, as compared to the commercially available tablets. Based on the results it could be
concluded that microemulsion formulation could be used as a possible alternative to traditional oral formulations of
Glimepiride to improve the dissolution rate and hence its bioavailability.
INTRODUCTION
The compounds with powerful pharmacological activity
have been screened by remarkable progress of modern
technology, such as structure-based drug design (SBDD),
combinatorial chemistry and high throughput screening
(HTS) in recent years. These compounds often show high
lipophilicity and slight water solubility. In case of the
formulations for oral administration, the lipophilic drugs
(Class II drugs) show the poor gastrointestinal absorption
because of the low solubility or dissolution rate to water
which inturn leads to low and variable oral bioavailability
(Chiou et al., 1976). Therefore, even though such
compounds have powerful pharmacological activity, the
expected clinical efficacy is sometimes not experienced. In
order to increase the clinical efficacy of such lipophilic
compounds at the time of oral administration, many trials
which improve the gastrointestinal absorption and raise
bioavailability have been made. Different technologies
involved for solubility improvement are pulverization,
crystal polymorphism selection, salt formation, solid
dispersion, mixed pulverization, complex formation agent
* For correspondence: Surjyanarayan Mandal,
Tel: 02668-262327
E-mail: surjya05n08@gmail.com.
Surjyanarayan Mandal and Snigdha. S. Mandal : Microemulsion Drug Delivery System: A Platform for Improving
Animals
Animal experiments were approved by Animal ethical
committee, Ministry of Government of India, New Delhi,
India, with the permission number of 404/01/a/CPCSEA.
Male albino rats were obtained from Zydus Health Care,
Ahmadabad, India.
Methods
Solubility Studies: The solubility of Glimepiride in various
components like oils and surfactants was determined. 3 ml
1215
HLB Value
7.1
11.5
7.2
4.0
4.6
1.0
15.6
15.2
15.0
4.2
Solubility (mg/ml)
24.94 0.22
34.92 0.81
20.13 0.53
41.34 0.83
8.46 0.39
26.54 2.7
5.56 0.9
11.42 1.2
19.45 1.1
18.29 0.39
Surjyanarayan Mandal and Snigdha. S. Mandal : Microemulsion Drug Delivery System: A Platform for Improving
140
Solubility (mg/ml)
120
100
80
60
40
20
0
Microemulsion
Labrafil M 1944 CS
Cremophore RH 40
Transcutol P
Water
Vehicles
Km = 1:1
Km = 3:1
1217
Km = 2:1
Km = 3.5:1
Characterization
Results:
The
physicochemical
characteristics of the developed microemulsion appear in
Table 2. It was clear from the physicochemical data that
the developed system had low viscosity (~27.5 cP). From
the viscosity and electroconductive study it can be
concluded that the system is of o/w type. The refractive
index of the developed system (1.34) was almost same to
the refractive index of water (1.333). In addition, the
developed systems (10 and 100 times diluted) showed
percent transmittance >99%. The refractive index and
percent transmittance data prove the transparency of the
system. The nanometric size range of the particle was
retained even after 100 times dilution with water, which
Stability Study
Results of the stability study are shown together in Table 3.
No significant difference in the particle size,
%transmittance and % assay of the developed formulation
suggested optimized Labrafil M 1944 CS based
microemulsion was stable up to 3 months.
%Transmittance
Glimepiride ME
99.40.3
Refractive
index
Particle
size (nm)
Poly dispersibility
Index (PDI)
% Drug
Content
1.3330.02
23.60.3
0.3210.001
98.720.23
nd
% Assay
2 Month
99.60.21
23.60.27
98.120.18
4th Month
98.60.19
24.10.51
98.420.33
6th Month
98.80.18
25.30.34
98.190.22
4 Hr
99.40.3
24.30.3
98.650.41
24 Hr
98.90.15
24.60.18
98.550.19
4 Hr
99.00.3
23.60.3
98.670.16
24 Hr
98.10.22
22.90.24
98.270.27
Surjyanarayan Mandal and Snigdha. S. Mandal : Microemulsion Drug Delivery System: A Platform for Improving
1219
Conclusion
The developed microemulsion containing Labrafil M 1944
CS (8%), Cremophore RH 40 (32%), Transcutol P (8%),
and water (52%) was found to be transparent with a
particle size of 23.6 nm and was stable for 6 months.
Solubility of glimepiride by the o/w microemulsion was
increased to 5785 times to water. Results of in-vitro studies
showed significantly higher drug diffusion for developed
Microemulsion formulation compared to suspension of
commercially available tablet. Hence, it can be concluded
that the microemulsion formulation could be employed to
improve the dissolution by solubility enhancement and
hence the bioavailability of a poorly absorbed drug could
be improved. However, further studies in higher animals
and human being need to be performed before this
formulation can be commercially exploited.
Acknowledgements
The authors are thankful to Colorcon (Asia) Pvt Ltd, India
for supplying the oils, surfactants and cosurfactants.
References
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