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‫البقرة‬
Contributors
INTRODUCTION
? What is Glibenclamide

Glibenclamide is a sulfonylurea anti-

diabetic.
It is given by mouth in the treatment of type 2
diabetes mellitus and has a duration of action
up to 24 hours.
Sulphonylurea activate receptors on the β
cells of the pancreatic islets to release stored
insulin in response to glucose.
 Different trade names of
Glibenclamide available in the
markets
Trade name Company Dosage form

Daonil Aventis Pharma Tablet

Diaben Pharco Tablet

Diatab Spimaco Tablet

Dwabetic Modern Pharma Tablet

Glibil Hikma Tablet

Gliboral Menarini Tablet

Euglucon ABI Tablet

 Chemical structure

5-chloro- N-[ 2-[ 4- (cyclohexyl carbamoyls

sulfamoyl) phenyl] ethyl] -2- methoxy benzamide.
 Scope of work
Glibenclamide is readily absorbed from the
gastro intestinal tract following an oral
administration, It is metabolised, almost
completely in the liver to very weakly active.
So this investigation is an attempt to prepare
Glibenclamide as transdermal formulation
such as film, ointment, emulgel, and
emulsion.
 Moreover transdermal application
of Glibenclamide has the following
advantages over oral
administration :
Increasing bioavailability (by
avoiding hepatic metabolism).
 To avoid sever hypoglycemia.(4)
 To avoid gastrointestinal
disturbances .
Portal vein
Transdermal
absorption

Blood vessels
 Transdermal absorption
Skin

Oral Systemic circulation

)First pass effect(

G.I.T
,Stomach) Liver
(Intestine

Presystemic Completely Metabolized

Metabolism (first pass effect)
METHODOLOGY
UV Scanning of Glibenclamid
5mg of drug was dissolved in 10 ml of
resceptor media to prepare stock solution with
concentration of 500 µ g / ml.
Then 3 ml of the sample was scanned at wave
length between 200- 400 nm by using
resceptor media as a blank, the λ max which
was obtained was 305 nm.
Calibration curve of Glibenclamide

Different diluted solutions were prepared,

and the absorbance of each prepared
solution was measured
. spectrophotometrically at λ max 305 nm
The absorbance of each sample was plotted
.against the corresponding concentrations
Calibration factor (K) =
414.
Correlation coefficient (r) =
0.999991.
Slope = 0.002415

1.4

1.2
 Composition of the
Prepared Transdermal
Formulations
Water soluble bases:bases
Polyethylene glycol base: (U.S .P .XXII).

PEG 4000 6 gm
PEG 400 4 gm
 Emulsion bases (O/W
emulsion base)

Ethyl alcohol 0.3 g

Liquid paraffin 2g
Tween 80 0.4 g
Span 80 0.6 g
Glycerin 0.7 g
Water 6g

10 g
(Emulgel (O/W Emulgel

Liquid paraffin 2gm

Tween80 0.1gm
Water 7.7gm
Gelatin 0.2gm
10 gm
Composition of the Film
Substance Amount

Ethanol 18ml

Water 7ml

HPMC 0.4gm

PEG400 0.1gm

DRUG 0.056gm
 Part :1
Release studies
through the natural
rabbit skin
((in vitro study
Using Diffusion tester and natural rabbit
. skin
In case of ointment, emulsion and emulgel,
1gm of the tested formulation contains 5 mg
of Glibenclamide was weighed in a
diffusion cell (basket(. While the film was
(.cut into pieces (4.7 cm2 contains 5 mg
the dermal side was directed toward the
receptor compartment and the stratum
. corneum facing the donor compartment
Dissolution
Diffusion
Results
Amount Released of Glibenclamide from different
formulations via the natural rabbit skin
Base Amount of drug released in mg after the following time
interval (hrs)

1 2 3 4 5

Film 1.1175 1.5525 2.3715 2.607 2.9805

PEG 0.816 1.358 1.8 2.1735 2.3598

Emulgel 1.091 1.4685 1.86 1.9665

0.4965

Emulsion 0.3675 0.621 0.7425 0.78246 0.84456

3.5

PEG
3
 Kinetic data of Glibenclamide released from
different formulations using natural rabbit skin
Formula (Correlation coefficient (r The observed Slope
order

Zero order First order Diffusion order

Film 0.982433 0.964463 0.988248 diffusion 0.47805

PEG 0.978377 0.937858 0.994755 diffusion 0.37896

Emulgel 0.975294 0.925901 0.992642 diffusion 0.3709

Emulsion 0.935288 0.895765 0.968586 diffusion 0.111558

Pharmacokinetic parameters of
Glibenclamide released from
different formulations using
Formula
natural
Order
rabbit
Slope
skinK (T 1/2 ( hrs

Film diffusion 0.47805 0.47805 5.229578

PEG diffusion 0.37896 0.37896 6.597002

Emulgel diffusion 0.3709 0.3709 6.740361

Emulsion diffusion 0.111558 0.111558 22.40987

Conclusion of In-vitro study

The amount of Glibenclamide released from

different bases can be arranged according to
the following descending order:

Film > PEG Ointment > Emulgel>Emulsion

 PART 2
In-Vivo Studies
In-Vivo Studies methodology

24 alive
Rabbits
were used
for testing
the release
of
Glibenclami
de in
fasting and
random
A- The Prepared B- Shaved rabbit
Film

C- Blood D- Glucometer
* Blank and oral, the reading was the average of three rabbits in each experiment.
** Transdermal , the reading was the average of six rabbits in each experiment.
In-Vivo Studies Results
Comparison between oral and transdermal
Glibenclamide in blood glucose of fasting rabbits
Time (hrs(
Average Blood glucose mg/dl ( Fasting rabbits(

Blank* Oral* Transdermal**

0 116 128 123.3

1 111 63 95.2

2 110 42 67.8

3 108 59 79.7

4 105 72 95.3
 F ig .2 :

1 4 0 .0

1 3 0 .0 1 2 8
1 2 3 .3
1 2 0 .0
116
1 1 0 .0
 Comparison between average of oral and
transdermal Glibenclamide in blood glucose
of Random rabbits
Time (hrs( Average Blood glucose mg/dl ( Random rabbits(

Blank* Oral* Transdermal**

0 92 100 99.4

1 97 54 81.0

2 109 52 76.2

3 96 63 86.7

4 103 70 90.8

5 98 85 96.0

6 97 90 104.4
 F ig : ) T h e

1 2 0 .0

1 1 0 .0

1 0 0 .0 19 09 0.4
Conclusion of in-vivo study

It can be concluded that,

transdermal Glibenclamide
(Film) did not cause sever
Hypoglycemia comparing with
oral Glibenclamide
administration.
 General Conclusion
From the Previous studies, it can be
concluded that:
1. Transdermal route is an effective route
for administration of Glibencalmide.
2.Transdermal route is a convenient and
acceptable route for large number of
patients.
3.Glibenclamide is better to be
formulated as film.
 
 Recommendation

Accordingly, we recommended that

1)Further studies must be done for those
new formulations.
2)Researches must be proceeded for
clinical trials on human to demonstrate
the most appropriate doses.