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ABSTRACT
Irbesartan is a non peptide specific competitive antagonist of the angiotensin II
receptor used orally for treatment of hypertension. Irbesartan exhibits low
bioavailability related to its poor water solubility. The present research carried out
for crystal modification irbesartan in the presence of different additives, to
improve the solubility and dissolution rate. The additives used for the crystal
modification were PVP K30, PEG 4000, HPMC and Tween 80. The modified
crystals were characterized by Scanning electron microscopy, FT-IR
spectroscopy, differential scanning calorimetry and X-ray diffraction. The
comparative solubility and dissolution rate of modified crystals and the untreated
irbesartan were studied. The SEM results different morphology (size and shape)
in the presence of additives. FT-IR spectra of untreated irbesartan when
compared with the various crystals obtained in the presence of additives showed
no significant change in their characteristic peaks. Also DSC spectra showed
slight change in the melting endotherm of modified crystals and the XRD spectra
revealed slight change in diffraction pattern. The FT-IR, DSC and XRD indicate
crystal modification in the presence of additives. The modified crystals obtained
in the presence of PEG 4000 showed maximum solubility and dissolution rate
compared to other modified crystals and untreated irbesartan.
Keywords: Crystal modification, Irbesartan, FT-IR, DSC, Solubility, dissolution
rate.
INTRODUCTION
selective
crystals.
impurity interaction.
Crystallization of API by
presence
different
crystal
of
size,
[3-5]
additive
melting
can
affect
point,
the
solubility
pattern,
faces,
[8]
leading
to
alter
morphology.
System.
The
drug
exhibits
low
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106
solubility,
dissolution
rate
and
compaction
characteristics.
Fig.1. Irbesartan
Qualigens,
Mumbai
and
of
analytical
grade.
ethanol at
such
650C
as
hydroxypropyl
Solubility studies
electron
Whatmann
polyethylene
polyvinyl-pyrollidone
glycol
microscope
(PEG-4000),
(Jeol
Instruments,
Japan).
filter
paper,
suitably
diluted
and
Dissolution studies
Infrared spectroscopy
cm-1
type-2
apparatus,
(Paddle
type)
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0.50C.
1800, Japan.).
Preparation of compacts
Infrared spectroscopy
showed
characteristic
peaks
in
Fig.3.(a-h)
difference
The
in
the
crystal
morphology.
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108
189.210C,
of
temperature
190.070C,
and
endothermic
188.560C
peak
192.020C,
respectively.
towards
190.610C
lower
and
Shift
respectively,
untreated irbesartan.
Dissolution studies
respectively.
of
Compressional studies
undergo
the
Solubility studies
109
The
structural
X-ray
diffraction
modification.
pattern
However,
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CONCLUSION
Crystal modification of irbesartan was carried out in
the presence of additives. The modified crystals
showed the significant change in size and shape.
Solubility and dissolution rate of modified crystals
were markedly increased compared to untreated
(c)
ACKNOWLEDGEMENT
The Author are thankful to the Management and
Principal, IBSS College of Pharmacy, Malkapur for
providing necessary facilities to carried out this work.
Authors also thankful to Diya Labs, Mumbai and
(d)
(e)
(a)
(f)
Fig.2. SEM of (a) untreated irbesartan (b)
recrystallised from ethanol, (c) PVP-K30,
(d) PEG-4000, (e) HPMC and (f) Tween
(b)
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110
Fig.3. FT-IR spectra of : (a) untreated irbesartan, (b) recrystallised in ethanol, (c) PVP-K30, (d) PEG-4000, (e) HPMC
and (f) Tween80.
Fig.4. DSC thermogram: (a) untreated irbesartan, (b) recrystallised in ethanol, (c) PVP-K30, (d) PEG 4000, (e) HPMC
(f) Tween 80.
Fig.5. X-ray diffractrogram of: (a) untreated irbesartan (b) recrystallised in ethanol, (c) PVP-K30, (d) PEG 4000, (e)
HPMC and (f) Tween80.
111
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Table 1: Melting point, DSC and FT-IR data of modified crystals in the presence of additives
DSC data
Crystal forms
Untreated irbesartan
recrystallized from
ethanol
PVP K-30
PEG-4000
HPMC
Tween 80
M.P
(oC)
187189
189191
187189
186188
188190
191193
Characteristic peaks of IR
C=H
C=O
C=C
Stretch
Stretch
Stretch
(cm-1)
(cm-1)
(cm-1)
N-H
Stretch
(cm-1)
186.32
189.89
73.43
3436.51
2959.70
1732.65
1408.96
184.56
190.07
22.99
3436.51
2958.12
1732.61
1409.00
183.88
189.21
27.09
3430.43
2959.95
1732.95
1408.81
183.43
188.56
24.84
3423.28
2926.00
1732.95
1409.36
186.20
190.61
27.00
3422.68
2946.22
1732.76
1409.03
186.45
192.02
27.64
3430.27
2959.18
1732.82
1409.01
Fig. 6: Dissolution rate profile of untreated irbesartan and modified crystals in the presence of additives.
presence and absence of impurity. Int. J. Pharm.
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