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Current Drug Therapy, 2020, 15, 28-36

RESEARCH ARTICLE
ISSN: 1574-8855
eISSN: 2212-3903

Formulation and In Vitro Evaluation of Hesperidin-Phospholipid Complex

and its Antioxidant Potential

Bhupen Kalita1,* and Bhargab Nath Patwary1

1
Girijananda Chowdhury Institute of Pharmaceutical Science, Guwahati-781017, Assam, India

ARTICLE HISTORY
Received: June 28, 2018
Revised: November 02, 2018
Accepted: January 02, 2019
Abstract: Background: The recent trend of herbal drug delivery has been focused on developing
novel drug delivery carriers to address problems related to solubility, oral bioavailability, skin per-
meation and stability. The phyto-phospholipid complex (phytosomes®) technology has been used to
overcome the problems associated with many conventional herbal extracts.
Aim: The present work aimed to formulate phospholipid-complex of the flavanoid Hesperidin to
enhance its dissolution leading to enhanced oral bioavailability.
Methods: The complex was prepared by refluxing various molar ratios of hesperidin and PC fol-
lowed by solvent evaporation. The prepared complexes were evaluated for saturation solubility,
partition co-efficient and drug content. The free drug and phospholipid complexes were analyzed in
DSC. Surface morphology of the prepared complexes was viewed using SEM images. Selected
formulations were subjected to in vitro drug release study. Antioxidant effect was examined by free
radical scavenging method.

DOI:
10.2174/1574885514666190226155933
Keywords: Hesperidin, phospholipid complex, phytosomes, herbosomes, solubility, antioxidant.
Current Drug Therapy
Results: Solubility and partition coefficient of the prepared complexes were improved in compari-
son to free drug. Based on the results of solubility, partition coefficient and drug content, formula-
tion F2 was selected as an optimized batch. DSC thermograms confirmed the formation of phos-
pholipid complex. Free Hesperidin and Hesperidin-phospholipid complex (F2) showed 46.9 % and
78.20 % of drug release, respectively, at seven hours phosphate buffer (pH 7.4). The optimized
formulation showed concentration-dependent anti-oxidant property.
Conclusion: Results of the present study suggested that the phospholipid complex of Hesperidin
possesses the antioxidant potential and may be of potential use for improving the dissolution of
hesperidin and hence oral bioavailability.

herbal medicine, it may help in increasing the efficacy and

1. INTRODUCTION
The demand for plant-derived drugs seems to increase in
developing countries due to their medicinal values and eco-
nomic procurement. Plants have been used in a wide variety
of dosage forms since ancient time. Even after advancement
of standardization protocol and analytical sophistication,
herbal drugs are still exhibiting certain limitations such as
physicochemical favorability to design dosage form, bio-
pharmaceutical issues like delayed therapeutic response,
drug degradation during its passage from Gastrointestinal
Tract (GIT) to liver, inability to produce required drug con-
centration at the target site, requirement of relatively large
quantity of drug and chances of variability in herbal com-
pounds. If the novel drug delivery technology is applied in
*Address correspondence to this author at the Girijananda Chowdhury Insti-
tute of Pharmaceutical Science, Guwahati-781017, Assam, India;
Tel: +91-8486002671; E-mail: bhupenkalita@gips-guwahati.ac.in
reducing the side effects of various herbal compounds and
herbs. This is the primary motive in incorporating novel
methods of drug delivery in herbal medicines. Thus, it is
important to integrate a novel drug delivery system and
traditional herbal remedies to combat more serious diseases
[1].
Phytosomes® were significant research outcome in herbal
formulations that provide better pharmacokinetic and phar-
macodynamic behavior than conventional botanical extracts.
This technique utilized complex formation between phos-
pholipid molecules and herbal extracts or its constituents
producing a lipid compatible molecular complex soluble in
both water and lipid environment [2]. The dietary or essen-
tial phospholipids used for complexation uniquely resemble
the mammalian cellular phospholipids and hence are suffi-
ciently biocompatible [3]. It has been found that conven-
tional herbal extracts, when complexed with phospholipids,
have improved bioavailability. Thus, the problem of poor

2212-3903/20 $65.00+.00 ©2020 Bentham Science Publishers

Formulation and In Vitro Evaluation of Hesperidin-Phospholipid
Table 1. Formulation of hesperidin-phospholipid complex (HPC). Each batch was prepared in triplicate.
Formulation Ratio of Hesperidin to PC
F1 1.0:0.5
F2 1.0:1.0
F3 1.0:2.0
F4 1.0:3.0
absorption of phytoconstituents like flavonoids, xanthones
and terpenoids has been overcome by Phytosomes technol-
ogy [4]. The polar functional groups of the lipophilic guest
interact via hydrogen bonds and polar interaction with the
charged phosphate head of phospholipids, forming a unique
arrangement that can be evidenced by spectroscopy. As
phosphatidylcholine is a bifunctional molecule with hydro-
philic choline and hydrophobic phosphatidyl group, the cho-
line portion binds with the guest compound, while phos-
phatidyl portion envelopes the bounded part [5]. Applying
this technique, a number of successful attempts have been
reported those claimed enhanced oral/topical bioavailability
of silymarine [6], silybin [7], curcumin [8], rifampicin [9],
Aspirin [10], baicaline [11], quercetin [12], rutin [13], res-
veratrol [14], Naringenin [15], Embeline [16], etc.
Hesperidin is chemically hesperetin 7-rutinoside
(C28H34O15; MW: 610.56g/mol). It is slightly soluble in wa-
ter (1gm/50 litre), methanol and glacial acetic acid but freely
soluble in dilute alkalis and pyridine [17, 18]. Biological
effects of hesperidin include anti-inflammatory and analgesic
[19], anti-diabetic [20], sedative [21] and neuroprotective
[22]. Hesperidin holds potential in treating age-related macu-
lar degeneration, cataract and diabetic retinopathy [23].
Hesperidin has been regarded as a potential antioxidant from
the herbal source [24]. The reducing capacity of a compound
indicates its power to serve as an antioxidant [25, 26].
However, different types of antioxidant possess different
mechanisms of action to prevent oxidation of any compound
viz. prevention of chain initiation, decomposition of peroxi-
dases [27], binding of transition metal ion catalysts, inhibi-
tion of diene conjugates, prevention of continued hydro-
gen abstraction and radical scavenging antioxidant activity
[28].
Ameer et al. (1996) reported low bioavailability (<25%)
following oral administration of hesperidin [29]. The oral
bioavailability of hesperidin is affected by poor water solu-
bility which is further aggravated in the acidic environment
[30]. Another reason for lower oral bioavailability is that
hesperidin is substrates of the intestinal efflux protein, P-
glycoprotein (P-pg) [31], and intestinal and hepatic drug
metabolizing enzymes CYP450 [32]. Biopharmaceutic stud-
ies revealed that hesperidin possesses poor transmembrane
permeability [33, 34]. Manach et al., (2003) reported that
hesperidin needs to be converted to hesperetin by the beta-
glycosidases secreted by the intestinal flora for absorption
[35]. In the light of literature reports, the present study is
aimed to develop hesperidin-phospholipid complex to im-
prove solubility and dissolution of hesperidin and to evaluate
the antioxidant property of the complex.
Current Drug Therapy, 2020, Vol. 15, No. 1 29
Dichloromethane (ml) Temperature (°C)
40 60
40 60
40 60
40 60
2. MATERIAL AND METHODS
2.1. Materials
Hesperidin was purchased from Otto Chemicals, Mum-
bai, India. All the reagents and the solvents were of analyti-
cal grade and used as received. Distilled water was used
throughout the study.
2.2. Preparation of Hesperidin-phospholipid Complex
(HPC)
HPC was prepared in four different molar ratios of Hes-
peridin to soya lecithin as a source of phosphatidylcholine
(PC). Weighed quantities of hesperidin and PC were taken in
a 100 ml round bottomed flask and 40 ml of dichloro-
methane was added. The mixture was refluxed at a tempera-
ture not exceeding 60oC for 2 h (Table 1). The resultant clear
solution was poured into a petri dish and the solvent was
evaporated on a water bath for 15 minutes. The Hesperidin–
phospholipid complex was allowed to dry in room tempera-
ture overnight and then under the influence of desiccant for
24 hours to remove traces of solvent [36, 37]. Finally, each
batch was individually packed into tightly closed glass bot-
tles for further use.
2.3. Solubility Study
Excess amount of drug or HPC was taken and added to 5 ml
solvent (water, phosphate buffer pH 2.5, 7.4) in a tightly
capped glass vial. To mix properly, sample was constantly
agitated at 80 rpm at room temperature for 24 hr in a rotary
shaker (REMI). At the end of 24 hr, the samples were centri-
fuged at 1000 rpm. The supernatant liquid was separated and
from that, 0.5 ml transferred to 10 ml volumetric flask. The
volume was made up to the mark with distilled water. The
absorbance was determined using water as blank at the λmax
284 nm in a UV-Visible Spectrophotometer (Shimadzu 1800,
Japan) [38].
2.4. Partition Coefficient
The partition coefficient of hesperidin and the prepared
HPC was determined using n-octanol/water and n-
octanol/phosphate buffer (pH 7.4) as the partitioning me-
dium. The separating funnels were thoroughly cleaned, dried
and labeled and then 20 ml n-octanol and 20 ml aqueous
medium were added. To each separating funnel, 10 mg free
hesperidin or HPC were added. Then the funnels were
shaken in mechanical shaker up to 24hrs. After 24 hrs, the
samples were separated and the absorbance of the aqueous
fraction was measured at 284 nm after suitable dilution [39].
30 Current Drug Therapy, 2020, Vol. 15, No. 1
2.5. Determination of Drug Content
A quantity of HPC equivalent to 10 mg of free hesperidin
was weighed and added in 50 ml 0.2 M NaOH solution and
kept on magnetic stirring for 1 hour. The solution was fil-
tered through Whatman filter paper (0.45 µm). From the
filtrate, 1 ml solution was diluted to 10 ml with distilled wa-
ter and absorbance was measured at 284 nm [40].
2.6. Differential Scanning Calorimetry (DSC)
The thermal analysis of free hesperidin, physical mixture
of hesperidin and PC, and HPC were carried out using
Parkine Elmer, Jade, USA, DSC-4000 instrument. The sam-
ples (9 mg) were sealed in aluminum pans and the DSC
thermograms were recorded at a heating rate of 10°C/min
from 30°C to 350°C [40]. An empty pan served as reference
and Indium was used to calibrate the temperature.
2.7. In-vitro Drug Release Studies
Dissolution study was carried out in 900ml phosphate
buffer (pH 7.4) maintained at 37.5±0.5oC. The prepared HPC
formulations or free hesperidin were placed in the bottom
of each dissolution flask in the USP (Type II) dissolution
apparatus. The paddle is rotated at 50 revolutions per min.
5 ml samples were withdrawn at predetermined time inter-
vals (0-8 hr) and replaced with the same quantity of fresh
medium in order to maintain sink condition. The collected
samples are filtered using Whatman filter paper and then
diluted with pH 7.4 phosphate buffer. The absorbance was
measured at 284 nm in UV/Visible spectrophotometer. From
the absorbance data, the cumulative amount of drug dis-
solved at different time intervals was calculated using the
calibration curve.
2.8. Scanning Electron Microscopy
The surface morphology of hesperidin and formulation
was determined using a scanning electron microscope (JSM-
6360A, JEOL). The samples were lightly sprinkled on a
double adhesive tape stuck to an aluminium stub. The stubs
were then coated with platinum to a thickness of about 10Å
under an argon atmosphere using a gold sputter module in a
high- vacuum evaporator. Afterwards, the stub containing
the coated samples was placed in the scanning electron mi-
croscope chamber [41].
2.9. Antioxidant Activity Study of the Complex by Re-
ducing Power Method
The reducing power was determined according to the
method of Oyaizu [42]. To 1.0 ml of the HPC complex solu-
tion (at different concentration as 20, 40, 60, 80, 100μg/ml),
2.5 ml of 0.2 M-phosphate buffer (pH 6.6), and 2.5 ml of
(1% w/v) Potassium Ferricyanide [K3Fe (CN) 6] was added.
The mixture was incubated at 50ºC for 20 min and then al-
lowed to reduce to room temperature. Then 2.5 ml of 10%
w/v Trichloroacetic acid solution was added. The mixture
was centrifuged at 3000 rpm for 10 min. The upper layer of
the solution (2.5 ml) was mixed with 2.5 ml distilled water
and 0.5 ml ferric chloride (0.1% w/v), and the absorbance of
this mixture was measured at 700 nm. The intensity in ab-
sorbance could be the measurement of antioxidant activity of
Kalita and Patwary
the substance under test. The blank was also carried out in a
similar manner, using distilled water in the place of drug.
Increase in the absorbance of the reaction mixture indicated
the increase in reducing power. The activity was compared
with ascorbic acid, which was used as a standard antioxidant
[43].
3. RESULTS AND DISCUSSION
3.1. Preparation of HPC
The method for the preparation of HPC involved reflux-
ing followed by solvent evaporation (Table 1). The drug and
PC dissolved completely in dichloromethane and obtained a
clear solution. HPC was prepared in four different molar
ratios (0.5:1, 1:1, 1:2, 1:3) of Hesperidin to PC so as to get
the optimized formulation in terms of solubility, partition co-
efficient and drug content. The HPC complex obtained after
reflux and solvent evaporation was not free-flowing and off
white in colour. Phyto-phospholipid complexes are generally
prepared by using phytoconstituent and phospholipid in mo-
lar ratios ranging from 0.5 to 2 [44], though a 1:1 ratio have
been found to be most successful and hence most preferred
[45]. Maryana et al., (2016) reported a molar ratio of 1:5
produced silymarine-phospholipid complex with best phys-
icochemical properties [46]. Ittadwar and Puranik, (2017)
reported umbelliferone phytosomes development and opti-
mization using experimental design approach where three
different molar ratio of drug to PC i.e. 1:1, 1:2 and 1:3 were
employed. They found that the formulation at 1:2 molar ratio
to be the optimized batch on the basis of good solubility,
highest complexation rate leading to higher practical yield
and recovery [47]. The optimal complex of oxymatrine-
phospholipid was obtained at a molar ratio of 3:1 [48]. Tan
et al., (2012) employed a central composite design for proc-
ess optimization in the development of Evodiamine-
phospholipid complex (EPLC). Based on the results ob-
tained, the authors suggested that to develop a cost-effective
EPLC with high complexation rate, optimal values for phos-
pholipid-to-drug ratio (mol/mol) should be 2 [49]. Kalita and
Das (2015) prepared Resveratrol-phospholipid complex in
five different molar ratios; they found that a molar ratio of
1:0.75 showed best aqueous solubility, partition coefficient
and drug entrapment efficiency [14]. Mei et al., (2018) ad-
vocated that a molar or stoichiometric ratio of 1:1 is not al-
ways optimal for the formulation of phospholipid complexes.
For different types of drugs, we should experimentally adjust
the stoichiometric ratio of active constituents and phosphol-
ipids according to distinct purposes [50]. In the present
study, out of all combinations, HPC was best prepared using
a hesperidin to PC molar ratio of 1:1.
3.2. Solubility Study of Hesperidin in Complex form
The saturation solubility of the drug and HPC was stud-
ied in three different solvent systems (Table 2). The solubil-
ity of HPC was found to be significantly improved compared
to free hesperidin, and prominently in phosphate buffer pH
7.4, the solubility of HPC (F2) was significantly higher
(p<0.05) at 10.2 ± 1.27 compared to free hesperidin which
was only 0.62 ± 0.38. Whereas both free hesperidin and HPC
showed very less solubility in distilled water and even less in
acidic pH.
Formulation and In Vitro Evaluation of Hesperidin-Phospholipid
Table 2. Results of solubility, partition coefficient and drug content analysis of free hesperidin and hesperidin-PC complex (HPC).
Sample Solubility (mg/ml)
Distilled Wa- Phosphate Phosphate buffer
ter Buffer pH 2.5 pH 7.4
Free hesperidin 0.07 ± 0.08 0.02 ± 0.08 0.62 ± 0.38
F1 0.53± 0.33 0.18± 0.33 3.62 ± 1.04
F2 1.64± 0.42 1.03 ± 0.31 10.20 ± 1.27
F3 1.28 ± 0.54 0.59 ± 0.48 5.88 ± 1.35
F4 1.22 ± 0.46 0.62 ± 0.77 6.16 ± 1.52
3.3. Partition Coefficient
The apparent partition coefficients of Hesperidin in n-
octanol/water or basic buffer system are shown in Table 2.
The partition coefficient of Hesperidin in distilled water was
higher than in phosphate buffer pH 7.4. Further, the HPC
(F2) showed the partition coefficient value of 1.36 ± 0.84 in
n-octanol/water system, indicating a more balanced partition
coefficient value than free hesperidin favorable for drug dis-
solution and absorption. HPC (F2), in n-octanol/buffer me-
dium, showed more satisfactory results of partition coeffi-
cient at 0.96 ± 0.72. Results indicated higher hydrophilicity
of HPC compared to the free drug which is highly lipo-
phillic. From the solubility and partition coefficient studies,
the formulation F2 was found to be satisfactory compared to
all other formulations.
3.4. Percent Drug Content of the Formulations
Drug content of all HPC formulations was found above
80% (Table 2). The differences in drug content may be at-
tributed to the differences in the ratios of drug and phosphol-
ipid used in different batches of HPC. Formulation F1
showed highest drug content among all HPC formulations
followed by F2, F3 and F4 at 92.54%, 89.40%, 84.92% and
80.23%, respectively. Results showed that as the phosphol-
ipid fraction increased in F1 to F4, the drug content de-
creased. This may be due to the unbound phospholipid. A
novel protopanaxadiol (PPD)-phospholipid complex en-
riched with micelles by the addition of Labrasol was re-
ported by Xia et al., (2013) [51]. The entrapment efficiency
of the prepared complexes was 93.53% ± 2.28%. The ratios
of drug to PC and the level of Labrasol affected the entrap-
ment efficiency. Keerthi et al., (2014) reported the entrap-
ment efficiency of Ashwagandha phytosomes at 90.1% pre-
pared by the ethanol method. Entrapment efficiency was
used in the optimization of the level of PC in the complexes.
Their experiments revealed that the optimum ratio of drug
to PC in the phytosomes was at 100 mg:400 mg. They
also reiterated that further increase in the lipid concentration,
the Entrapment efficiency decreased, indicating that the
lipid concentration did not help in entrapping the drug
into the matrix [52]. Similar results obtained in the present
study in drug content analysis, indicated that the ratio of
drug to PC have an impact on physical bonding of drug and
PC and hence on total drug content of phyto-phospholipid
complex.
Current Drug Therapy, 2020, Vol. 15, No. 1 31
Partition Coefficient Drug Content
(%)
n-octanol/distilled n-octanol/phosphate
water buffer (pH 7.4)
3.13 ± 0.65 0.03 ± 0.46 --
2.63 ± 0.92 1.55 ± 0.46 92.54 ± 4.01
1.36 ± 0.54 0.96 ± 0.32 89.40 ± 6.012
2.38 ± 0.77 1.38 ± 0.56 84.92± 4.024
2.25 ± 0.65 1.35 ± 0.33 80.23± 5.06
3.5. DSC Study
In order to characterize the association of Hesperidin
with PC, DSC analysis was performed. The result of the
DSC test suggested the binding of Hesperidin and PC in the
complex (Fig. 1). The DSC thermogram of Hesperidin ex-
hibits a sharp endothermic peak at 260.37°C with an onset
temperature of 253.41°C indicating the melting point and a
broad endothermic peak at 102.01°C corresponding to the
loss of water. On the other hand, complex showed two peaks
at 201.40°C and at 235.19°C which were different from the
peaks of the individual components of the complex. The
DSC thermograms of the phospholipid complexes of some
phytoconstituents like ursodeoxycholic acid, L-carnosine and
naringenin also demonstrated similar result [37, 53, 54]. The
original peaks of phytoconstituent and phospholipids disap-
pear from the DSC thermogram of complex and phase transi-
tion temperature is lower than that of pure drug and phos-
pholipids. These changes in DSC thermograms suggested the
necessary interaction of hesperidin with PC in the formation
of phospholipid complexes.
3.6. In Vitro Drug Release Study
The Hesperidin-phospholipid complex showed better
dissolution profile than the pure Hesperidin (Fig. 2). Unlike
free Hesperidin which showed a total of only 46.9 % drug
release, formulation F2 showed 78.20 % drug release at the
end of 8h of dissolution study in phosphate buffer pH 7.4.
Dissolution of the drug is a prerequisite for GI absorption of
the drug. The increased dissolution rate of F2 in comparison
to free hesperidin would lead to increased oral bioavailability
of hesperidin from the HPC formulation.
3.7. Scanning Electron Microscopy
Scanning electron microscopy images of the complex
suggest the uniform surface texture of the HPC (Fig. 3).
There were no repeating units observed suggesting the
amorphous nature of the phospholipid complex of hes-
peridin. It was observed that the drug particles were uni-
formly associated with the phospholipid forming complexes
which were irregular in shape and separately no drug parti-
cles could be visible because of the complex formation.
3.8. Antioxidant Study of Prepared Complex
The antioxidant study was carried out by the reducing
power method. The absorbance of the standard antioxidant
32 Current Drug Therapy, 2020, Vol. 15, No. 1 Kalita and Patwary

Fig. (1). DSC thermogram of hesperidin, physical mixture of hesperidin and PC, and phospholipid complex (F2). (A higher resolution / col-
our version of this figure is available in the electronic copy of the article).

Fig. (2). In vitro drug release profile of free hesperidin and hesperidin phospholipid complex (HPC) in phosphate buffer (pH 7.4). (A higher
resolution / colour version of this figure is available in the electronic copy of the article).
Formulation and In Vitro Evaluation of Hesperidin-Phospholipid Current Drug Therapy, 2020, Vol. 15, No. 1 33

Fig. (3). SEM images of phospholipid complex of hesperidin. (A higher resolution / colour version of this figure is available in the electronic
copy of the article).

Table 3. Antioxidant activity of Hesperidin-PC complex.

Sample Absorbance at Different Concentrations

20 μg/ml 40 μg/ml 60 μg/ml 80 μg/ml 100 μg/ml

Standard 0.212 ± 0.032 0.384 ± 0.046 0.521 ±0.037 0.678 ± 0.039 0.748 ± 0.036
(Ascorbic Acid)

HPC 0.175 ± 0.044 0.295 ± 0.041 0.398 ± 0.033 0.487 ± 0.072 0.582± 0.056
*Values are expressed in Mean ± SD, n=3.

Fig. (4). Reducing power as indicated by the absorbance value. (A higher resolution / colour version of this figure is available in the elec-
tronic copy of the article).

(Ascorbic acid) was compared with the prepared hesperidin 4, 6-triperidyl–s–triazine complex to intensively blue colored
phospholipid complex (Table 3). Ferric reducing antioxidant ferrous complex in acidic medium. Hence, any compound
power measures the ability of antioxidants to reduce ferric 2, which is having redox potential lower than that of redox pair
34 Current Drug Therapy, 2020, Vol. 15, No. 1
Fe (III)/Fe (II) can theoretically reduce Fe (III) to Fe (II)
[55].
In this assay, the yellow colour of the test solution
changes to various shades of green and blue, depending on
the reducing power of each compound. The presence of re-
ducers (i.e. antioxidants) causes the reduction of the
Fe3+/ferricyanide complex to the ferrous form. Therefore,
measuring the formation of Perl’s Prussian blue at 700 nm
can monitor the Fe2+concentration [56].
From the result obtained, it was interpreted that hes-
peridin-PC complex showed a concentration-dependent in-
crease in anti-oxidant activity at applied concentrations- 20,
40, 60, 80 and 100 µg/ml (Fig. 4). The results of antioxidant
effect were found insignificant between HPC and ascorbic
acid (P>0.05). Maiti et al., (2009) prepared hesperetin (the
aglycone of hesperidin) phytosome with hydrogenated phos-
phatidylcholine and studied its antioxidant activity and
pharmacokinetics in CCl4 intoxicated rats. Finally, they re-
ported that phytosome had shown high antioxidant activity.
Also, pharmacokinetic studies showed better bioavailability
[57].
CONCLUSION
Herbal drugs with inadequate aqueous/lipid solubility
lead to limited bioavailability and subtherapeutic pharmacol-
ogical effect. Phospholipid complex of flavonoids class of
herbal drugs improves the physicochemical solid state and
solution properties as well as stability that lead to enhanced
dissolution in the physiological fluid. The hesperidin-
phospholipid complex demonstrated enhanced solubility in
basic buffer system and very balanced partition coefficient
values suggesting the ability of such complex with good
membrane permeation efficiency. In vitro drug release pro-
file suggested that the prepared complexes possess increased
dissolution in a sustained release manner compared to free
hesperidin. The complex showed a concentration-dependent
increase in anti-oxidant activity which was statistically simi-
lar to ascorbic acid. The enhanced solubility and dissolution
of the prepared hesperidin-phospholipid complex would im-
prove the oral bioavailability of hesperidin.
ETHICS APPROVAL AND CONSENT TO
PARTICIPATE
Not applicable.
HUMAN AND ANIMAL RIGHTS
No animals/humans were used for studies that are basis
of this research.
CONSENT FOR PUBLICATION
Not applicable.
AVAILABILITY OF DATA AND MATERIALS
  hanced therapeutic potential of naringenin-phospholipid complex in
The data supporting the finding of the study are available
within the article.
FUNDING
 
None.
Kalita and Patwary
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Declared none.
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