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INTRODUCTION
28 July 2018, Herbal medicines have been widely used all over the world since
Revised on 18 August 2018,
Accepted on 08 Sept. 2018 ancient times and have been recognized by physicians and patients for
DOI: 10.20959/wjpps201810-12435 their better therapeutic or biological value as they have no or fewer
adverse effects as compared with modern medicines. Phytosome is a
*Corresponding Author novel approach to drug delivery system that addresses the limitations
Patial Aman of the traditional drug delivery systems (Suryawanshi, 2011).
Dreamz College of Phytosome is a newly introduced patented technology developed to
Pharmacy, Mandi Himachal
incorporate the standardized plant extracts or water-soluble
Pradesh.
phytoconstituents into phospholipids to produce lipid compatible
molecular complexes called phytosomes (Manach et al., 2004; Habbu et al., 2013 and
Pandey et al., 2010). Most of the biologically active constituents of plants are water soluble
molecules. However, water soluble phytoconstituents (flavonoids, tannins, Xanthones,
Glycosides) are poorly absorbed when taken orally or when applied topically either due to
their large molecular size which cannot be absorbed by passive diffusion or due to their poor
lipid solubility, severely limiting their ability to pass across the lipid‐rich biological
membranes, resulting in poor bioavailability (Manach et al., 2004). Phytosomes provide
better absorption and bioavailability than the conventional herbal extracts. When a
stoichiometric amount of the phospholipid was made to react with purified herbal extract in
an aprotic solvent, phytosomes were formed (Keerthi et al., 2014). Phytosomes, complex of
natural active ingredients and phospholipid increase absorption of herbal extracts or isolated
active ingredients when applied topically or orally. Phytosome are cell like structures which
result from the stoichiometric reaction of the phospholipids (phosphatidylcholine and
phosphatidylserine) with the standardized extract or polyphenolic constituents (flavonoids,
terpenoids, tannins and xanthones) in a non-polar solvent, which are better absorbed, utilized
and as a result produce better results than conventional herbal extracts (Bhattacharya et al.,
2009; Singha et al., 2011). Phospholipids are the main building blocks of life and are one of
the major components of cellular membranes. In general, they are considered as natural
digestive aid and carriers for both polar and non-polar active substances (Pandey et al.,
2010). Most of phospholipids possess nutritional properties, like phosphatidylserine which
acts as a brain cell nutrient, phosphatidylcholine which is important in liver cell regeneration.
Soya phospholipids have lipid reducing effect and hydrogenated phospholipids serve as basis
for preparation of stable liposomes because of their amphiphilic character (Schmitt and
Lecithin, 2008). Phytosomal formulations enhance the bioavailability of active
phytochemical constituents as they are now permeable and can cross the lipid rich
biomembranes quite easily and the active components of the herbal extracts are well
protected from destruction by digestive secretions and gut bacteria. Therefore, with help of
phytosomal preparations, the amount of standardized plant extracts and phytoconstituents
administered in body through several routes are required in fewer amounts for good
therapeutic activity (Singha et al., 2011). With the advancements in science, the phytosomes
have gained importance in various fields like pharmaceuticals, Cosmeceuticals and
nutraceuticals in preparing different formulations such as solutions, emulsion, creams,
lotions, gels, etc. Several companies involved in production and marketing of phytosome
products’ are Indena, Jamieson natural resources (Neffulusa, 2009). Many approaches have
been developed to improve the oral bioavailability, such as inclusion of solubility and
bioavailability enhancers, structural modification and entrapment with the lipophilic carriers.
The phytosome technology developed by Indena meets this challenge by markedly enhancing
the bioavailability of selected phytomedicines (Venkatesan et al., 2000; Longer et al., 1985;
Sharma et al., 2005).
Rationalization of Phytosome
The source of Polyphenolic active compound (flavonoids) has been used in traditional
medicine since ancient time against various diseases, including hepatic disorder,
respiratory diseases and rheumatism.
However the main drawback associated with polyphenolic compounds are their less
absorption from GIT. Less absorption of polyphenolic active compound (flavonoids) is
due to high aqueous solubility and multiple ring arrangement of the molecules which
leads to poor bioavailability. Some of the polyphenolics are highly lipophilic and possess
inadequate dissolution in aqueous GI fluids (Havsteen et al., 2002).
Thus phytosomes has designed to improved solubility and permeability using
phospholipids.
Phytosome approach has shown to overcome such problems and become more
bioavailable as compared to conventional herbal extract owing to their enhanced capacity
to cross the lipoidal biomembrane and finally reaching the systemic circulation. Hence
phytosome is fastly growing attractive way of delivering botanicals based drugs and
neutraceuticals (Bhattacharya and Ghosh, 2009).
Preparation of phytosomes
Phytosome are prepared by reaction of 2-3 moles of phospholipid preferably
phosphatidylcholine or phosphatidylserine with the phytoconstituents like terpenoids
(cafestol) or flavonoids (Catechins or quercetin) in an aprotic solvent such as dioxane, ethyl
acetate or acetone. Lyophilization, freeze drying, precipitation with aliphatic hydrocarbons or
evaporation of solvent under vacuum can be carried out for the isolation. (Loggia et al.,
1996). Phospholipid to phytoconstituents ratio is normally 1:1 to synthesize a phytosome.
Merits of Phytosomes
1. They enhance the absorption of lipid insoluble polar phytoc8onstituents and shows better
bioavailability; hence they have significantly greater therapeutic benefit.
2. They improve the absorption of active constituent which have further reduce dose
requirements.
3. Phosphatidylcholine used in preparation of phytosomes, besides acting as a carrier also
acts as a hepatoprotective, hence giving the synergistic effect when the hepatoprotective
substances are employed.
4. Chemical bonds are formed between phosphatidylcholine molecules which added
nutritional benefit of phospholipids.
5. They have appreciable drug entrapment.
6. Significantly greater clinical benefits.
7. Assured delivery to the tissue. (Srikanth et al., 2011)
Demerits of Phytosome
Phytoconstituent is rapidly eliminated from phytosome (Saha et al., 2013 and Battacharya
et al., 2009).
Properties of Phytosomes
Following are some of the important properties of phytosomes:
Physiochemical properties
1. Phytosomes are prepared by reaction of stoichiometric amount of phospholipid with the
standardized plant extracts as substrate. The spectroscopic data reveals that the
phospholipid substrate interaction is due to the formation of hydrogen bond between the
polar head (i.e., phosphate and ammonium group) and the polar functionalities of the
substrate (Tripathy et al., 2013).
2. The size of Phytosome varies from 50 nm to a few 100μm (Patel et al., 2013).
3. Phytosome when treated with water assumes a micellar (spherical) shape resembling
liposome and photon correlation spectroscopy (PCS) reveals this liposomal structures
acquired by phytosome (Jain, 2005).
4. The H1NMR and C13 NMR data deduced that the fatty chain gives unchanged signals
both in free phospholipid and in the complex, which indicates that long aliphatic chains
are wrapped around the active principle producing lipophilic envelope (Dayan and
Touitou, 2000).
5. The complexes are often freely soluble in aprotic solvents (Chloroform and
Dimethylsulfoxide) moderately soluble in fats, insoluble in water and relatively unstable
in alcohol. But the phytosomes of certain lipophilic phytoconstituents like curcumin has
shown increase in water solubility upon complexation with phospholipid (Maffei et al.,
1994).
Biological properties
Phytosome are novel complexes which are better absorbed and utilized; hence they produce
more bioavailability and better result than the conventional herbal extract or non-complex
Evaluation of Phytosomes
Characterization
The following are the characterization techniques used for Phytosomes in characterizing its
physical attributes.
2) Spectroscopic Evaluation
The spectroscopic evaluations are widely employed in order to confirm the formation of
complex between phytoconstituents and the phospholipid moiety as well as to study the
corresponding interaction between the two.
1
H-NMR: The complex formation between the active phytoconstituents and the
phosphatidylcholine molecule can be estimated by this method. Bombardelli et al.,
studied the NMR spectra of phytosome complex in non polar solvents. There is a marked
change in 1H-NMR signal originating from atoms involved in the formation of complex,
without any summation of the signal peculiar to individual molecules. The signals from
protons belonging to the phytoconstituents are broadened. In phospholipids there is
broadening of signals while the singlet corresponding to the N-(CH3)3 of choline
undergoes an up field shift (Bombardelli et al., 1991).
13
C-NMR: In the 13C NMR of the phytoconstituents and the stoichiometric complex
with the phosphatidylcholine when recorded in C6D6 at room temperature all the
phytoconstituents carbons were invisible. The signals corresponding to the glycerol and
choline portion are broadened and some are shifted, while most of the resonance of the
fatty acid chains retains their original sharp line shape.
Successful product
S. No. Natural Source Phyto-constituents Pharmacological action Dose forms/Dose Reference
Withanolides
(Steroidal lactones):
Antibacterial,
Withanone, withaferin A,
antioxidant, aphrodisiac, Ashwagandha Keerthi et
1 Ashwagandha withanolides.
liver tonic and anti- phytosomes. al., 2014
Alkaloids: ashwagandhine,
inflammatory
cuscohygrine, anahygrine,
ropine.
Antioxident,
Rutin Vankudri et
2 Rutin quercitine glycoside antiplatelate and
phytosome/100 mg al., 2016
Antidiabetic
Boswellic acid
phytosome
Boswellia Antimicrobial and Sahu A.R et
3 Carrier:lecithin,
Serrata Counter irritant activities al., 2015
Phospholipon 90 G,
cholesterol
4 Silybium Silybin, Silycristin, Isosilibin, Hepatoprotective, Silybin Farinacci et
maranium Silydianin, silibinin cirrhosis and acute and phytosomeTM al., 2009
chronic inflammation (Siliphos ®)/ 120- (22)
200 mg
Neutraceutical,
Epigalloctechin, catechin, Anticancer, Antioxidant, Green tea
Camellia Pierro et al.,
5 epicatechin-3-O-gallate, Hepatoprotective, Anti- PhytosomesTM /400
sinensis (Tea) 2009 (25)
epigalloctechin-3-O-gallate diabetic and anti- mg
inflammatory
Cognition enhancer,
Gingko flavonoids, Gingoic Raynaud’s disease, Gingkoselect
Pandey et
6 Gingko biloba acid of Antiasthmathic, PhytosomeTM /120
al., 2010
gingkoflavonglucosides cardioprotectives, mg
antiinflammatory.
Crateegus Nutraceutical, Hawthron
Pandey et
7 oxyacanthoides Hyperin, Quercitin Cardioprotective and PhytosomeTM /100
al., 2010
(Hawthron) antihypertensive mg
Antioxident,
Olea europaea Oleaselect Pandey et
8 Verbascosides, tryosol antihyperlipidimic,
(olive tree) PhytosomeTM al., 2010
anticancer
Echinacea Echinacosides and high
Nutraceutical, Echinacea Bombardell
9 angustifolia molecular weight
Immunomodulator PhytosomeTM et al., 1991
(Cone flower) polysaccharides(inulin)
Terminalia Anti –aging, wound Sericoside
Bombardeli
10 serica (Silver Sericoside healing, antioedema, PhytosomeTM /3%
et al., 1974
cluster leaf) anti-inflammatory gel
Anti-inflammatory,
Glycyrrhiza Glycyrrhetinic acid Pandey et
11 Glycyrrhetinic acid antierythemic, anti-
glabra (Mulethi) PhytosomeTM al., 2010
irritant, skin infection
Centella triterpinoid
Centella asiatica Skin disorder, antiulcer, Bombardeli
12 Asiatic acid PhytosomeTM /60-
(Brahmi) wound healing et al., 1974
120 mg
Curcumin
Curcuma longa Anti- inflammatory, PhytosomeTM , Kohli et al.,
13 Curcumin
(turmeric) osteoarthritis, anticancer Curcuvet® /250 mg 2005
and 360
Naringenin
Citrus aurantium Maiti et al.,
14 Naringenin Antioxidant PhytosomeTM/100m
(bitter orange) 2006
g/kg
Swertia Swertia Havsteen et
15 Xanthones 26 Antioxidant
alternifolia PhytosomeTM- al., 2002
Anti- inflammatory,
Vaccinum
Antioxidant, Mirtoselect
16 myrtillus 5,26
Anthocyanosides vasoprotective, PhytosomeTM
(Bilbery)
antidiabetic
Serenoa repens Non – cancerous Salbalselect
Pandey et
17 (Saw palmetto Phytosterols prostate enlargement, PhytosomesTM /320
al., 2010
berries anticancer mg
Melilotus Anti- inflammatory,
Melilotoside, flavanoid and LymphaselectTM /2 Pandey et
18 officinalis (sweet antioedema,
terpenoids to 60 mg al., 2010
clover) thrombophlebitis
Ammi visnaga Microcirculation Pandey et
19 Visnadine VisnadexTM
(Khella) improver, anticellulite al., 2010
Santalum album Ximenynic acid, ethyl Microcirculation Ximilene Bombardeli
20
(Sandal wood ximenynate improver Ximenoil et al., 1974
PhytosomesTM
Vasoactive,
Fraxinus ornus Esculoside
21 Esculoside (Esculin) Microcirculation Saha et al.,
(Flowering ash) PhytosomesTM
improver, anticellulite
Puerarin and
Radix puerariae Anti inflammatory, Battacharya
22 Puerarin phospholipid
(kudzu root) cardiovascular diseases et al., 2009
complex
Panicum Mineral salts, vitamins,
Antistress, bcauty food Millet Pandey et
23 miliaceum unsaturated fatty acid,
for skin, nails and hairs PhytosomesTM al., 2010
(Millet) aminoacid
Vaccinium Anthocyanoside tocotrienol Antioxidant, improves
Vita Blue Pandey et
24 angustifolium complex, citrus bioflavonoid, vision, memory
PhytosomesTM al., 2010
(Blue berry) alpha lipoic acid enhancer
Immunomodulator
Ginseng Pandey et
25 Panax ginseng Ginsenosides activities and
PhytosomesTM al., 2010
neutraceutical
CONCLUSION
The effectiveness of herbal extracts in terms of potency can be improved by the value added
phytosome formulations which is a patented technology (Indena, Italy) also known as
herbosome. For gastrointestinal absorption a drug should have sufficient water solubility and
lipid solubility. The polyphenolic flavonoids are well known for their diverse therapeutic
effects but either less water solubility or insufficient lipid solubility are the hurdles in
developing dosage form. Problems of this type are avoidable through the benefits of this new
technology. Therapeutic effect of herbal constituent can be obtained at significantly lower
dose in comparison to conventional herbal extract. The review enlightened the ongoing
research and also through rays of hope that in near future many of the traditional herbal
extract can be converted to effective modern medicine.
REFERENCES
1. J. A. Saonere Suryawanshi., 2011; “Phytosome: An emerging trend in herbal drug
treatment”. Journal of Medical Genetics and Genomics, August 2011; 3(6): 109-114.
2. Manach C, Scalbert A, Morand C, Polyphenols, food sources and bioavailability,
American journal of clinical nutrition, 2004; 9: 727-747.
3. Prasanna Habbu, Smita Madagundi, Ramesh Kulkarni, Preparation and evaluation of
Bacopae phospholipid complex for antiamnesic activity in rodents, Drug invention today,
2013; 5: 13-21.
4. Pandey S, Patel K, Phytosomes: Technical revolution in phytomedicine, International
journal of Pharm Tech Research, 2010; 6: 627‐31.
5. Keerthi B, Prasuna Sundari Pingali, Dr. Prathima Srinivas, 2014; “Formulation and
Evaluation of Capsules of Ashwagandha Phytosomes” Int. J. Pharm. Sci. Rev. Res.,
29(2), November – December 2014; Article No. 25, Pages: 138-142.
6. Bhattacharya S. Phytosomes: emerging strategy in delivery of herbal drugs and
nutraceuticals. Pharma Times, 2009; 41: 9-12.
7. Anupama Singha, Vikas Anand Saharanb, Manjeet Singha, Anil Bhandaria: Phytosome:
Drug Delivery System for Polyphenolic Phytoconstituents Iranian Journal of
Pharmaceutical Sciences Autumn, 2011; 7(4): 209-219.
8. Pandey S, Patel K. Phytosomes: technical revolution in phytomedicine. Int J Pharm Tech
Res., 2010; 2: 627-31.
9. Tripathy S, Patel D, Baro L, Nair S (2013) A review on phytosomes, their
characterization, advancement and potential for transdermal application, Journal of Drug
Delivery and Therapeutics, 2013; 3: 147-152.
10. Patel A, Tanwar Y, Rakesh S, Patel P (2013) Phytosome: Phytolipid Drug Delivery
System for Improving Bioavailability of Herbal Drug. Journal of Pharmaceutical Science
and Bio scientific Research, 2013; 3: 51-57.
11. Maffei Facino R, Carini M, Aldini G, Bombardelli E, Morazzoni P, et al. (1994) Free
radicals scavenging action and anti-enzyme activities of procyanidines from Vitis
vinifera. A mechanism for their capillary protective action. Arzneimittelforschung, 1994;
44: 592-601.
12. Loggia RD, Sosa S, Tubaro A et al., (1996). Anti-inflammatory activity of some gingko
biloba constituents and of their phospholipids-complexes. Fitoterapia., 3: 257-273.
13. Schmitt H. Lecithin and phospholipids – healthy and natural powerful nutrients. Wellness
Foods Europe 2008; NUMBER June/July: 24-9].
14. Manach C, Scalbert A, Morand C, Polyphenols, food sources and bioavailability,
American journal of clinical nutrition, 2004; 9: 727-747.
15. Thorne Research, Natural factors, and Naturesherb [Product-Information. Nefful's anti-
aging skin supplement-a natural skin regimen, the need for a natural antiaging skin
regimen. Available athttp://www.neffulusa.com/downloads/pdf/2009/A
R_Ingredient_Information.pdf: Accessed on 21st April 2011.].
16. N. Venkatesan, B. S. Babu, S. P. Vyas. Protected particulate drug carriers for prolonged
systemic circulation–a review. Indian J. Pharm. Sci., 2000; 62: 327-333.
17. M. A. Longer, H. S. Ching, J. R. Robinson. Oral delivery of chlorthiazide using a
bioadhesive polymer. J. Pharm. Sci., 1985; 74: 406-411.