Beruflich Dokumente
Kultur Dokumente
17
Department of Chemistry, H. N. B. Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India; 2Department
of Pharmaceutical Sciences, H. N. B. Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India
Abstract: Development of amphiphilic drug-lipid complexes is a potential approach for improving therapeutic efficacy of
the drugs by increasing solubility, release profile and oral bioavailability. Quercetin (3, 3', 4', 5, 7-pentahydroxyflavone), a
polyphenolic flavonoid, shows several biological effects like anti-inflammatory, anti-cancer, antiproliferative, antimutagenic and apoptosis induction but its use is limited due to its low aqueous solubility. To overcome this limitation, a
value added phospholipid complex of quercetin was developed to improve its aqueous solubility for better absorption
through the gastrointestinal tract and this might result in improved bioavailability. The quercetin-phospholipid complex
thus prepared was evaluated for various physico-chemical parameters like infra red spectroscopy (FT-IR), differential
scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM) and solubility
study. The In vitro antioxidant activity was also studied. The phospholipid complex of quercetin was found to be fluffy
and porous with rough surface in SEM. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex.
The water solubility of quercetin was improved by 12 folds (from 3.44 g/ ml to 36.81 g/ ml) in the prepared complex.
There was no statistical difference between the quercetin complex and quercetin in the In vitro anti-oxidant activity, indicating that the process of complexation did not adversely affect the bioactivity of the active ingredient.
Keywords: Amorphous product, antioxidant activity, phosphatidylcholine, phospholipid complex, quercetin, solubility
behavior.
1. INTRODUCTION
Upon oral ingestion, a drug is dissolved into the gastric
fluid (hydrophilic environment) initially followed by the
permeation across the biological membranes (lipophilic environment) and finally reaches the blood stream. Most of the
biologically active polyphenolic phytoconstituents are associated with the problem of either poor absorption or the poor
permeation through the biological membrane, thereby limiting their absorption and overall availability to the body system [1, 2]. Poor absorption may be due to their poor water
solubility. While the poor permeation may be due to the nature of structure of the drug (multiple-ring molecules like
many herbal drugs may be too large to be absorbed by
simple diffusion) or due to the poor miscibility with oils and
other lipids thereby, severely limiting their ability to pass
across the lipid-rich outer membranes of the enterocytes of
the small intestine [3, 4]. For good bioavailability, a herbal
drug must have an adequate hydrophilicity (for dissolution in
to gastrointestinal fluid) as well as an adequate lipophilicity
(to permeate across the lipidic biomembrane).
Flavonoids are a widely distributed group of polyphenolic compounds characterized by a common benzo-pyrone
structure. Flavonoids have a broad pharmacological profile
*Address Correspondence to this author at the Department of Chemistry, H.
N. B. Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India;
Tel: +91 1346 252229; Fax: +91 1346 252174;
E mail: msmrawat@gmail.com
1875-6220/12 $58.00+.00
wall transfer, in the organism [4, 23, 24]. Among the phospholipids, phosphatidylcholine (PC) is an important natural
carrier which can play a major role to improve solubility and
dissolution profile of the drug. It is compatible with pharmaceuticals, highly bioavailable and also exerts its own therapeutic benefits (like hepatoprotection). Moreover, it is also
an excellent emulsifier that enhances the bioavailability of
constituents with which it is co-administered [23, 25].
The present study deals with the development of quercetin-phospholipid complex with the aim of improving the
aqueous solubility of quercetin for better absorption through
the GI tract, which might result in improved bioavailability.
The prepared complex was characterized for various physico-chemical parameters FTIR, DSC, XRD, Solubility, SEM
and the In vitro antioxidant activity.
OH
O
HO
OH
OH
R2
CH2
O
CH2
P
CH2
CH3
CH
C
O
Quercetin
OH
R1
Singh et al.
CH2
CH3
CH3
Phosphatidylcholine
Quercetin-Phospholipid Complex
19
50. 0
45
40
35
30
1468.74
%T
25
1236.30
1091.50
3435.63
20
1738.81
15
10
2850.22
2918.11
Ph ospholipiod-1
0. 0
4000. 0
3600
3200
2800
2400
2000
1800
cm -1
1600
1400
1200
1000
800
600
450.0
600
450.0
600
450.0
600
450.0
(a)
89. 0
85
80
75
1015.31
824.16
70
%T
2360.41
65
60
1385.28
1199.93
55
3325.06
1169.08
1319.87
50
1264.77
1522.24
1614.99
45. 0
Que rcetin
4000. 0
3600
3200
2800
2400
2000
1800
cm -1
1600
1400
1200
1000
800
(b)
82. 1
80
75
70
822.69
65
60
2360.34
55
1471.62
1653.66
3391.88
%T
1733.84
50
1199.95
1087.44
45
40
35
2850.49
2918.27
30
25. 0
4000. 0
3600
3200
2800
2400
2000
1800
cm -1
1600
1400
1200
1000
800
(c)
53. 5
50
45
40
35
721.52
970.76
30
%T
25
1468.02
20
1237.07
1091.28
15
3413.46
1739.56
10
2850.06
2917.82
0. 0
4000. 0
3600
3200
2800
2400
2000
1800
cm -1
(d)
1600
1400
1200
1000
800
Singh et al.
Reduction in melting point and enthalpy account for increased solubility and reduced crystallinity of the drugs [30,
31]. This phenomenon can be assumed the interactions between component and the phospholipid in the complex system and can be considered as indicative of drug amorphization and/ or complex formation as supported by IR spectroscopy results also.
(a)
(b)
(c)
Fig. (3). DSC Thermograms: (a) Phospholipid (b) Quercetin (c) Quercetin- Phospholipid Complex
Quercetin-Phospholipid Complex
21
Fig. (4) shows the X-ray diffraction patterns of the quercetin, phospholipid and the complex. In the X-ray diffractogram quercetin showed intense diffraction peaks of crystallinity at a diffraction angle of 2 and suggested that the drug
is present as a crystalline material. The phospholipid showed
a single diffraction peak. A total drug amorphization was
induced by complex formation where X-ray diffraction patterns of quercetin-phospholipid complex were characterized
only by large diffraction peaks in which it is no longer possible to distinguish the characteristic peaks of the drug. The
results, confirmed that quercetin is no longer present as a
crystalline material and its phospholipid complex is in the
(a)
(b)
(c)
Fig. (4). X-ray diffraction patterns: (a) Phospholipid (b) Quercetin (c) Quercetin-Phospholipid Complex.
Singh et al.
(a)
(b)
Sample
Aqueous Solubility
n-Octanol Solubility
(g/ml)
(g/ml)
Quercetin
3.44
52.17
Quercetin complex
36.81
51.92
Quercetin-Phospholipid Complex
BHA;
Quercetin;
Quercetin-Pc Complex.
tion of the drug. Further, it was found that, there was no statistical difference in the percent inhibition of DPPH between
quercetin and its complex on all the dose levels. This indicates that, the bioactivity was maintained when quercetin
was complexed with phospholipid and the production process of the complex did not change or destroy the molecular
structure of active ingredient (quercetin) in the complex. As
these amphiphilic drug-lipid complexes have been reported
to be stable and more bioavailable, the phospholipid complex of quercetin may serve as a value added herbal drug
delivery system.
[6]
[7]
[8]
[9]
[10]
CONFLICT OF INTEREST
Declared none.
[11]
ACKNOWLEDGEMENTS
The authors are thankful to the Department of Science
and Technology, Government of India for the research grant
(SRSO/ HS/ 72/ 2006). The authors acknowledge LIPOID
GmbH Germany for providing the gift sample of phosphatidylcholine for the research work. Facilities provided by
UGC-DAE Consortium for Scientific Research, Indore (India), are gratefully acknowledged.
[12]
[13]
[14]
[15]
[16]
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