Hisperedin Emulosomes
Hisperedin Emulosomes
Hisperedin Emulosomes
ABSTRACT
Objectives: The objective of the present study was to increase the hesperidin gel. The in vivo pharmacokinetic and pharmacodynamic studies
solubility of poorly soluble drug hesperidin and to increase the efficacy were found to be more efficient for the hesperidin loaded emulsomal gel
of the drug by loading hesperidin in emulsomal topical gel. Methods: when compared to the marketed formulation. Conclusion: Hesperidin
Hesperidin was loaded into emulsomes by using ethanol injection method. emulsomal gel has shown a significant increase (p<0.05) in activity when
The optimized formulation of emulsomes was evaluated by SEM, FT-IR, compared to the marketed formulation.
DSC, P-XRD, in vitro drug release, ex-vivo skin permeation studies, in vivo Key words: Hesperidin, Emulsomes, Topical gel, In vitro drug release,
pharmacokinetic and pharmacodynamic studies. Results: The SEM study Pharmacokinetic and pharmacodynamic studies.
shows the emulsomes were tiny and spherical in structure. The particle Correspondence
size and zeta potential of the optimized formulation was found to be 50nm Y. Sarah Sujitha
and -1.8mV and in vitro drug release was found to be 98.6% for 6 hrs. The Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam,
optimized emulgel was prepared by using different gelling agents Carbopol (Women’s University), Tirupati-517502, Andhra Pradesh, INDIA.
934 and HPMC. The prepared gels were found to be homogenous and skin Phone no: +91 9494462070
permeation studies was found to be 98.9% for 4 hr, with skin permeation Email: suji.sarah@gmail.com
efficacy bearing flux value 12.3µg/cm2/h when compared to the pure DOI: 10.5330/ijpi.2020.4.87
INTRODUCTION
Hesperidin is a flavanone glycoside consisting of the flavone hesperetin enhanced bioavalibilty due to their reduced size. Emulsomes are a new
bound to the disaccharide rutinose which is highly detected in very young generation of colloidal carrier composed of solid lipid surrounded
tissues of the fruit. It was first discovered by leberton that hesperidin by phospholipid bilayers which represent a novel lipoidal vehicle of
is natural flavones present in citrus fruits. Hesperidin is an inexpensive particulate structure with improved loading capacity for drugs and
byproduct of citrus family and it occurs in all plants including nuts, biologics containing components that have been safely used to deliver
seeds, vegetables, flowers and barks.1,2 Hesperidin belonging to family medications to people.12,13 A key feature of emulsomes is that this internal
Fabacea, Beulaceae and Lamiaceae.3,4 The sugar group makes hesperitin core is composed of a lipid in a solid or liquid crystalline phase, rather
more water-soluble than hesperidin. Hesperidin has been reported to than an oil-in-fluid phase, at 25°C i.e., high hydrophobic drug loading
influence a wide variety of biological functions. For example, hesperidin in the internal solid lipid core and the ability to encapsulate water-
induces apoptosis and suppresses proliferation in human cancer cells,
soluble medicaments in the aqueous compartments of surrounding
inhibition of tumour development in various tissues including the skin.
phospholipid layers.14 Emulsomes may be used for parenteral, oral,
Many of these beneficial effects of hesperidin can be attributed to its
occular, rectal, vaginal, intranasal, or topical delivery of either fat-
antioxidant activity. Hesperidin enhances microcirculation, possess
soluble or water-soluble substances.15 The particle size distribution of
antioxidant effect, improve venous tone, anti-inflammatory, analgesic,
blood lipid lowering, assist healing of venous ulcers and also used for emulsomes, based on differential weight per cent, is in the range of 10-
the treatment of haemorrhoids, chronic venous insufficiency and exhibit 250 nm, making them suitable for intravenous administration. They can
pronounced anticancer activities.5-7 Edema is a complex biological encapsulate water-soluble pharmaceuticals in the aqueous compartments
response produced by the body tissues, which is produced during any of the outer phospholipid layers, while their cores can be loaded with
harmful stimuli and irritants, injuries. Inflammation is characterized high levels of hydrophobic drugs. Emulsomes thereby increase the
by pain, swelling, redness.8,9 Chronic inflammation causes the heart solubility and improve the bioavailability of lipophilic drugs and their
diseases, rheumatoid arthritis, hay fever and it is also a common organization facilitates sustained or controlled drug release. Therefore,
manifestitation in some infectious diseases like leprosy, tubercolosis, emulsomes may serve as efficient drug delivery systems because
asthma, inflammatory bowel disease and many auto immune diseases. they exhibit good biocompatibility, biodegradability, stability, high
However NSAIDS are used to treat the inflammation but the usage entrapment efficiency and sustained drug release. Emulsomes have main
is limited due to the undiseable able side effects on gastric, renal, advantages of high drug loading capacity, improved pharmacological
cardiovascular system.10,11 activity, site specificity and reduced toxicity. To assess the performance
Emulsomes are smaller in nano size when compared to other vesicular of emulsomes in improving the bioavailability and prolonging systemic
drug delivery systems like ethosomes, phytosomes and they show exposure of hesperidin, we prepared emulsomes containing hesperidin
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Sujitha and Muzib.: Topical Nanogel Loaded with Hesperidin Emulsomes
and evaluated their pharmacokinetic properties and in vivo drug delivery Evaluation of the emulsomes
performance. The prepared emulsomes were evaluated for per cent drug content, SEM,
FTIR, DSC, Zeta size, zeta potential and in vitro drug release study.
MATERIALS AND METHODS
Materials Preparation of stock solution
Hesperidin was obtained as a gift sample from Virdev Pharma Pvt. Ltd., 100 mg of hesperidin was dissolved in 100 ml phosphate buffer. Dilutions
Gujarat. Stearic acid, soya lecithin and cholesterol were purchased from were made to prepare 1µg, 2µg, 3µg, 4µg, 5µg, 6µg, 7µg, 8µg, 9µg, 10µg
SD. Fine-chem Ltd. ethanol and tween 80 was purchased from Merck by using a buffer. Then the absorbance of these different concentrations
limited, Mumbai. HPLC acetonitrile was purchased from HiMedia. of hesperidin was estimated in UV visible spectrophotometer at 285 nm.
Triethanolamine, Glycerine and Methylparaben and Propylparaben
Determination of drug content
have purchased from Merck Limited, Mumbai. Micro-organisms
10 mg of emulsomes were taken and add 10 ml of phosphate buffer 7.4.
(Staphylococcus aureus, E.coli, Proteus vulgaris, Bacillus subtilis) obtained
Sonicate the solution for 5 min and stirred for 30 min. Then the solution
from HiMedia.
was filtered. Dilutions were made and the absorbance was measured at
285 nm using UV visible spectrophotometer.
Methods
Preparation of emulsomes
SEM analysis
Emulsomes were prepared by the ethanol injection method. Required
Morphology of the nanoparticles (emulsomes) was characterized by
quantities of hesperidin, stearic acid, cholesterol and soya lecithin were scanning electron microscopy (SEM). The emulsomes were mounted on
taken and dissolved in 10 ml of ethanol (Table 1). Take 10 ml of phosphate aluminium stubs and examined using SEM.17
buffer in another beaker. Now slowly inject this ethanol solution
containing hesperidin into buffer solution while stirring. Continue the Differential scanning calorimetry
stirring until the organic phase gets evaporated. Then the solution was Small amounts of dried Hesperidin emulsomes powder and pure
subjected to centrifugation. Then collect the sediment and lyophilize the hesperidin was crimped in a standard aluminium pan and heated from
product. Emulsomes were prepared which were spherical in shape. 25 to 400°C at a heating rate of 10°C/min under constant heating.18
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Zeta size and zeta potential of drug release was found to be 98.6% for 6 hr for F5. Cumulative
The particle size and the zeta potential of the optimized emulsomes percentage drug release of emulsomes is given in the Figure 3.
formulation was measured using the (Horiba) particle size analyzer,
Drug content
the samples were diluted in triplicates and the size of the optimized F5
The drug content of the prepared gels from X1-X5 was found to be in the
emulsomes was found to be 50 nm. The zeta potential of the formulated
range of 92-96 %. The drug content of prepared emulsomes is shown in
emulsomes was found to be -1.8mV which indicates that the formulation
the Table 3.
was stable.
Homogeneity
In vitro drug release The prepared gels when observed visually they have shown no aggregates
All emulsomes formulations were subjected to in vitro drug release and the gel formed was uniform.
studies, the cumulative percentages of drug release were obtained by
taking a plot between the time on the x-axis and cumulative percentage pH
of drug release on the y-axis. The release studies were performed for The pH for the formulations of gel X1-X5 showed 6.8 to 7.0±0.2 this
all the formulations pure drug, F1, F2, F3, F4, F5 and F6. The amount indicates that the prepared gels were neutral and there is no skin
0 0 0 0
3 77.3 91.3 40
values were expressed as mean ±SEM. P<0.05 compared with disease control,
ANOVA (Fc>Ft) there is a significant difference.
Figure 2a: DSC of pure hesperidin.
Figure 2b: DSC of hesperidin emulsomes. Figure 3: Comparative in vitro dissolution profile of different hesperidin
Figure 2a,2b: DSC Differential scanning calorinetry themograms. loaded emulsomes formulations, mean ±SD, n=3.
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Sujitha and Muzib.: Topical Nanogel Loaded with Hesperidin Emulsomes
Viscosity
The viscosity of gel formulations was measured by using a Brookfield
viscometer and the viscosity of the prepared gels was found to be in the
range 8640 to 27960 cps as the concentration of the carbopol polymer
increases the viscosity of the gel increases gradually. The viscosity of
prepared emulsomes gel using different concentrations of carbopol and
HPMC is shown in the Table 3.
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CONFLICT OF INTEREST 19. Girish K, Asish D. Design, Development and evaluation of ion-activated in-
situ gel of moxifloxacin hydrochloride. Asi J of Pharma and Clin Research.
2019;3:94-103.
The authors declare that there are no conflict of interest. This research has
20. Liu Y, Sun C, Hao Y, Jiang T, Zheng L, Wang S. Mechanism of dissolution
not received any specific grant from any agency in public, commercial, enhancement and bioavailability of poorly water-soluble celecoxib by
not for profit sectors. preparing stable amorphous nanoparticles. J Pharm and Pharmaceu Science.
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Article History: Submission Date : 05-08-2020; Revised Date : 11-09-2020; Acceptance Date : 03-10-2020.
Cite this article: Sujitha YS, Muzib YI. Preparation of Topical Nano Gel Loaded With Hesperidin Emulsomes: In vitro and in vivo Studies Int. J. Pharm.
Investigation, 2020;10(4):500-5.
International Journal of Pharmaceutical Investigation, Vol 10, Issue 4, Oct-Dec, 2020 505