Phytosome

Submitted by:-
Surya prabhakar singh
M. Pharma 2nd semester
Institute of pharmacy
Bundelkhand university
Jhansi.
Submitted to:-
Dr. SUNIL KUMAR PRAJAPATI
( PROF. & READER )
Institute of pharmacy
Bundelkhand university
Jhansi.
PHYTOSOME
surya prabhakar singh - phytosome

 Introduction
 History of phytosome
 Why need phytosome
 Principle , structure and composition
 Phytosome V/S liposome
 Chemical, biological properties
 Advantage & disadvantage
 Mechanism
 Method of preparation
 Formulation
 Evalution
 Application
 Patented and market product
 Future aspect
 Reference
CONTENT

 Phytosome are noval drug delivery system. The term “phyto” means plant
and “some” means cell-like.Phytosomes are little cell like structures.
 This is advanced form of herbal formulations which contains the
bioactive phyto constituents of herb extracts surround and bound by a
lipid.
 Most of bioactive constituents are water soluble compounds like
flavonoids, glycosides because of their water soluble property and
lipophilic outer layer it shows better absorption and produce better
bioavailability.
INTRODUCTION

 Phytosome technology emerged in 1989 and sparked revolution in delivery of
herbal phyto-consttitutents.
 Over the past century scientific technology has established the composition of
flavonoids ,tannin, poly-phenolics and terpenes are present in plant but their poor
solubility and hydrolytical instability in water and organic solvents at
physiological, very poorly aborbed both orally and topically.
 Bioavailability can be improved by using new delivery system which can enhance
the rate and extent of solubilization into aqueous intenstinal fluid and capacity to
cross biomembranes.
History of phytosome

 The phytosomes process is a small cell in itself .
 Water soluble phyto -constitutent can be converted into lipid
compound molecular complex and therefore are aptly called
PHYTOSOME.
Reason are ;-
 Multiple-ring large size molecules - can not be absorbed by
simple diffusion.
 Poor miscibility.
WHY NEED PHYTOSOME ?

 Solving by phytosome
 Water-soluble phyto constituents can be converted into lipid-
compatible molecular complexes.
 Phytosomes are more bioavailable .
 Phytosomes are lipid-compatible molecular complexes.
 They have been used to deliver liver protecting flavonoids
because they can be made easliy .

 Phosphatidylcholine (or phosphatidylserine) is a bifunctional compound. The
phosphatidyl moiety is lipophilic and the choline (serine) moiety is hydrophilic in
nature. This dual solubility of the phospholipid makes it an effective emulsifier.
 Thus, the choline head of the molecule binds to these compounds while the lipid
soluble phosphatidyl portion comprising the body and tail which then surrounds
the choline bound material.
 Hence, the phytoconstituents produce a lipid compatible molecular complex with
phospholipids, as shown (also called as phytophospholipid complex)
Principle of phytosome

 Phytosome structure contain the active ingredients of the herb
surrounded by the phospolipids.
 The presence of the surfactant i.e the phospolipid in the molecule
which are shielded from water triggered degradation while at the
same time, allows obtaining a higher adhesion of the product itself to
the surface it comes into contact with and a better interaction of
various molecules with cell structure.
 •The size of phytosomes varies from 50 nm to a few hundred μm.
STRUCTURE OF PHYTOSOME

 Phytosome (Phospholipids + Herbal extract) In a aprotic solvent
( Do not contain O-H / N-H bond such as Acetone & DMSO)
 Ratio - ( 1:1) / (2:1)
•Phospholipids is a complex molecule responsible for formation of cell membrane &
comprises of Glycerol and phosphate group. It is derived from Glycine max.
•Example - Phosphatidyl choline
•Phosphatidyl serine
•DLPC ( Dilauryl phosphatidyl choline)
 Herbal extracts including Flavonoids,Terpenoids,Polyphenolic glycoside,Alkaloids,
Volatile oils
COMPOSITION

 Phosphatidylcholine are widely used because of their certain therapeutic value in
case of liver diseases, alcoholic steatosis, drug induced liver damage and hepatitis.
Phospholipids are also employed as natural digestive aids and as carriers for both
fat miscible and water miscible nutrients.
 Phosphatidylcholine is a bifunctional molecule with hydrophilic choline and
hydrophobic phosphatidyl group the choline group head binds with the compound,
while phosphatidyl portion envelopes the bounded part.

PYTOSOME VS LIPOSOME

Phytosome vs Liposome
PHYTOSOME LIPOSOME
In this the active chemical
constituent molecules are anchored
through chemical bonds to the polar
head of phospholipids.
In this active principles is dissolved
in the medium of cavity or in the
layer of membrane.
Chemical bonds are formed. No chemical bonds are formed.
In phytosome, phosphatidylcholine
and plant compound form 1:1 or
2:1 complex depending on
substance.
In this hundred or thousands
of phosphatidylcholine
molecules surround the water
soluble molecule.
Phytosomes are much better
absorbed than liposomes
showing better bioavailability.
Bioavailability of
liposomes is less than
phytosomes.
Contents of phospholipids is less
higher.
Contents of phospholipid is much
higher.surya prabhakar singh - phytosome

 Phyosome is a complex between natural product and natural
phospholipid.
 The phytosome complex is obtained by reaction of suitable amount
of phospholipid and the substrate in appropriate solvent such as
glycerol.
 The main phospholipid-substrate interaction is due to formation of
hydrogen bonds between polar head of phospholipid and polar
functionalities of substrate.
 When treated with water, they assume a micelle shape, forming
structures which resembles liposomes.
CHEMICAL PROPERTIES

 Phytosomes are advanced forms of herbal products that are better absorbed, utilized
and as a result produce better results than conventional herbal extracts.
 Freely soluble in non-polar and aprotic solvent; Solvents in which the hydrophilic
moiety is not present.
 Moderately soluble in fats.
 Insoluble in water.
 Phytosomes can accommodate the active principle that is anchored to the polar
head of the phospholipids, which finally becomes an integral part of the membrane.
 The increased bioavailability of the phytosome over the non complexed botanical
derivatives has been demonstrated by pharmacokinetics studies or by
pharmacodynamic tests in experimental animals and in human subjects.
BIOLOGICAL PROPERTIES

 Marked enhancement of bioavailability
 Valuable components of the herbal extract are protected from destruction by
digestive secretions and gut bacteria.
 Assured delivery to the tissues.
 Dose requirement is reduced due to the absorption of chief constituent.
 Phytosomes shows better stability profile because chemicalbonds are formed
between phospolipid molecule and phytoconstituent.
 Phospolipid used in the phytosome process beside acting as a carrier also
nourishes the skin because it is essential part of the cell membrane.
ADVANTAGE

 Phospatidylcholine used in the preparation of phytosomes, beside acting as a
carrier also act as a hepatoprotective,hence giving the synergistic effect when
hepatoprotective substance are employed.
 Phytosomes are widely used in cosmetics due to there more skin penetration
and have lipid profile.
 By enhancing the solubility of the bile to herbalconstituent, phytosomes
facilitates the liver targeting.
 Phytosomes are better able to transition from a hydrophilic environment into the
lipid friendly environment of the enterocyte cell membrane and from there into the
cell, andthus can be used for systemic targeting.

 When adminstered orally or topically they limit their bio-availbility
 Phyto constitutents is quickly eliminated from phytosome,
Phytoconstituent is rapidly eliminated from phytosomes. The duration of
action is short.
DISADVANTAGE

 The lower absorption and bioavailability of polyphenolic constituents mainly
due to two factors. These chief constituents are number of ringed molecule
and are not too much small that it will absorbed by diffusion process. Second
factor is that flavonoid molecule or chief constituents of polyphenols have
poor solubility with lipids. These are the limitations that inhibit their
absorption through biological membrane.
 Phytosome technology is mainly result with complexation of polyphenols
with phospholipid in 1:1 ratio or 1:2 results in the formation of phytosomal
complex with lipid covering around the constituents.
MECHANISM OF PHYTOSOME
TECHNOLOGY

 Phospolipids
 Eg: Soya Phosphatidyl choline, Egg Phosphatidyl choline,
 Dipalmityl Phosphatidyl choline, Distearyl Phosphatidyl choline.
 Aprotic Solvent
 Eg: Dioxane, Acetone, Methylene Chloride
 Non Solvent
 Eg: n-hexane and other aliphatic hydrocarbon
 Alcohal
 Eg: Ethanol, Methanol
Different Additives used in
formulation of
Phytosomes

Phytosomes are prepared by reacting natural or synthetic
phospholipids with active components like bioflavonoid,
flavolignan and polyphenolic constituents.
Solvent Evaporation method is the most common
technique used for the preparation of phytosomes
METHOD OF PREPARATION

 Phospholipids
 Solution of phospholipidsin organic solvent
 with drug extract
 Drying
COMMON STAGE OF PREPARATION

Formation of thin film
Hydration
Formation of phytosomal suspension

Method of Preparation
1. Solvent evaporation method
2. Rotary evaporation technique
3. Anti solvent precipitation technique
1- SOLVENT EVAPORATION METHOD-
 Particular quantity of drug polymer and phospolipid can be taken into
spherical bottom flask and reflux with specific solvent at a temperature
50-60ºC for 2 hrs.
 The mixture may be concentrated to 5-10 ml to get the precipitate whch
can be filtered and collected.
 •The dried precipitate phytosome loaded can be placed in amber colored
glass bottle and store at room temperature.

Drug and soya lecithin
↓
Refluxed with 20ml of acetone at a temperature 50-60 degree for
2hours
Concentrate mixture to 5-10ml
Obtain the precipitate
Filter and collect
phytosomes obtained
Solvent evaporation method:

 • The particular quantity of drug polymer and phospolipid can be
dissolved in specific solvent in a rotary spherical bottom flask followed by
stirring for 3 hours at temperature not exceeding 40ºC.
 • Thin film of the sample can be obtained to which n-hexane is added
continuously stirred using a magnetic stirrir.
 • The precipitate phytosome loaded obtained can be placed in amber
colored glass bottle and stored at room temperature.
2) Rotary Evaporation Technique

Drug and soya lecithin
↓
Dissolved in 30ml of tetra hydrofuran
↓
stirring for 3hours at a temperature not exceeding
40degree
↓
Thin film is formed
↓
Add n-hexane with stirring
↓
Precipitate obtained
↓
Dry and pass through mesh
↓
Phytosomes formed
Rotary evaporation technique:

 The particular quantity of drug, phospolipid and polymer may be taken into a
spherical bottom flask and reflux with specific solvent at a temperature not exceeding
60ºC tor 2 hours.
 The mixture can concentrated to 5-10ml.
 n-hexane can be added carefully with continuously stirring to
 get the precipitate which has filtered and collected and stored in vaccum desiccator
overnight.
 The dried precipitate is crushed in mortar and sieve through #100 meshes.
 The dried precipitate phytosome loaded can ne placed in amber colored glass bottle
and stored at room temperature.
Anti solvent Precipitation Technique

Drug + soya lecithin
Refluxed with20ml dichloromethane at 60
degree for 2hrs.
Concentrate mixture to 5-10ml
Add hexane 20ml
Filter the ppt formed. Dry, crush and pass
through #100
Antisolvent precipitation technique:-

Can be formulated – orally
Topically
The formulation tips shown here-
FORMULATION
Soft gelatin capsule
Topical dosage form
Hard geltin capcule

 Its represent an ideal solution to formulate Phytosome®
complexes. The Phytosome® complex can be dispersed in
oily vehicles to obtain suspensions to be filled in soft gelatin
capsules.
 Vegetable or semi-synthetic oils can be used to this
purpose. Indena recommend a granulometry of 100% <200
μm to best perform capsule production.
 According to Indena experience, not all the Phytosome®
complexes behave in the same way when dispersed in oily
vehicles and when the oily suspension is filled in the soft
gelatin capsules; for this reasons preliminary feasibility trials
should be performed to select the most suitable vehicle.
Soft gelatin capsules

 The Phytosome® complex can be formulated in hard gelatin
capsules as well. A direct volumetric filling process (without
precompression) can be applied, even if the apparently low
density of the Phytosome® complex seems to limit the
maximum amount of powder that can be filled into a capsule
(usually not more than 300 mg for a size 0 capsule).
 With a piston tamp capsule filling process, however, it is
possible to increase the amount of powder which can be filled
in a capsule, but precompression might affect the
disintegration time.
 A preliminary dry granulation process is advisable define the
best manufacturing process.
Hard gelatin capsules:

 The Phytosome® complex can be formulated topically as well. The ideal process
to incorporate the Phytosome® complex in emulsion is to disperse the
phospholipidic complex in a small amount of the lipidic phase and add it to the
already created emulsion at low temperatures (not higher than 40°C).
 The Phytosome® complexes are dispersible in the main lipidic solvents employed
in topical formulations.
 In case of formulations containing a limited amount of lipids, the Phytosome®
complex might also by dispersed into the watery phase, and again added to the
final formulation at temperature lower than 40°C.
Topical dosage forms

 Dry granulation represents the ideal manufacturing process to obtain tablets with higher
unitary doses and with suitable technological and biopharmaceuticalproperties.
 However, due to the limited flowability, potential stickiness and low apparent density of the
Phytosome® complex, a direct compression process can be applied only for low unitary
doses; note that whenever a direct compression process is applied, the Phytosome®
complex should be diluted with 60-70% of excipients to optimize its technological properties
and to obtain tablets with appropriate technological and biopharmaceutical characteristics.
On the other hand, wet granulation should be avoided due to the negative effect of water
and heat (granulation/ drying) on the stability of the phospholipid complex.
Tablets:

 Particle size
 Entrapment Efficiency
 FTIR Spectrographic Analysis
 Differential Scanning Calorimetry (DSC)
 Drug content
 Scanning Electron Microscopy
 Stability study
Evaluation of phytosomes

Particle size
 The average diameter and zeta potential of the phytosome loaded may be
each measured employing a Zetasizer ZEN 3600 at a fixed scattering angle of
90º at 25ºC.
Entrapment Efficiency
 Phytosome loaded can be diluted 1 fold with 10ml of solvent and so centrifuged
18,000 rpm for ½ hour at -4ºC using cooling centrifuge machine.
 The supernatent was isolated and the quantity of free drug may be determines by
UV/Visual spectrometry.
 To determine the entire quantity of drug 0.1ml of the phytosome loaded suspension
can be diluted in fuel, adusting the volume to 10ml.
 The entrapment efficiency may be calculated according to the subsequent formula.
 Entrapment efficiency(%) = (total amount of drug) – (amount of free
drug)×100/(total amout of drug)

 FTIR spectral data can be taken to determine the structure and chemical stability of
phytosome loaded, phospolipids, polymer and drug sample. Samples can be crushed
with KBr to get pellets at 600kg/cm2 pressure . Spectral scanning may be done in the
range between 4000-400cm-1.
 In the 1H-NMR spectrum, the signals of thecomplexes substances undergo a
strongbroadening .
 In the13 C-NMR spectrum, the signals of thecomplex substances as well as those of
thecholine and glycerin portion of the phospholipidcan no more be recorded .
 The phosphorous nucleus itself undergoes a bandbroadening which indicates that it is
involve incomplex formation.
FTIR SpectrographicAnalysis

Differential Scanning Calorimetry (DSC)
• The drug sample, phospholipids, polymer, physical mixture and phytosome loaded can
be placed within the aluminium crimp cell and heated at 10ºC/min from 0 to 400ºC in
the nitrogen atmosphere.
• Peak transition onset temperatures may be recorded by means of the instrument.
Drug Content
• Drug content of phytosome loaded can be determined by dissolving accurately
weighed 100mg of phytosome loaded in 10ml solvent.
• After appropriate dilution absorbance may be determined by UV
spectrophotometer.
• The drug content can be calculated by the subsequent formula:
Drug content(%) = (total amount of drug) – (amount of free drug) ×100/(total
amount of drug)

Scanning electron microscopy- SEM
• Scanning electron microscopy can be used to confirm particle size distribution
and surface morphology of the phytosome loaded.
• Dry samples may be placed on an electron microscope brass stub and coated
with gold in an ion sputtet.
• Digital pictures of phytosome loaded may be taken by random scanning of the
stub at 1000, 5000, 10000and 30000X magnifications

In Vitro and In vivo Entrapment
• In vitro and in vivo evaluation can be done according to therapeutic activity
measuerment parameters of the biologically active phytoconstituents present in the
phytosome loaded with the help of suitable animal models.
Stability Study
• stability study of optimized phytosomoal formulation was performed to
investigate the physical appearance and leak out of the drug from
phytosomes during storage.
• Optimised phytosomal formulation of drug extract was sealed in glass vials
and stored at refrigeration temperature (2-8ºC) and room temperature for a
period of 3 month.
• Sample from optimised phytosomal formulation were withdrawn at
definite time intervals and observed.

APPLICATION
 Silymarin phytosome:
 Most of the phytosomes are focused to silybum marianum which contains liver
protective flavonoids.
 The fruit of the milk thistle plant ( S. marianum family- steraceae) contains flavonoids
for hepato protective effect.
 Silymarin has been shown to have positive effects in treating liver diseases of various
kinds including hepatitis, cirrhosis, fatty infiltration of the liver and inflammation of
the bileduct
 Phytosomes of grape seed:
 Grape seed phytosome is composed of oligomeric polyphenols of varying
molecular size complexed with phospholipids.
 The main properties of procyanidin flavonoids of grape seed are an
increase in total antioxidant capacity and stimulation of physiological
defense of plasma.

Phytosomes of curcumin
• Maiti et al. developed the phytosomes of curcumin
(flavonoid from turmeric, Curcuma longa linn) and
naringenin (flavonoid from grape, Vitisvinifera).
• Phytosome of naringenin produced better antioxidant
activity than the free compound with a prolonged
duration of action

Phytosome of green tea:
 Green tea leaves (Theasinensis) is characterized by
presence of a polyphenolic compound
epigallocatechin 3-O-gallate as the key component.
 • These compounds are potent modulators of several
biochemical process linked to the breakdown of
homeostasis in major chronic-degenerative diseases
such as cancer and atherosclerosis.
 • Green tea also furnishes us with a number of
beneficial activities such as antioxidant,
anticarcinogenic, antimutagenic, hypocholesterolemic,
cardioprotective effects.

S.No Phytosome Product Phytoconstituent complex
with phosphatidylcholine
Dose Indications
1 Silybin Phytosome Silybin from Silybum 120mg Hepatoprotective, antioxidant for liver
marianum and skin
2 Ginko Biloba Phytosome 24% Ginkoflavanglycosides 120mg Protect brain and vascular lining; Anti
from Ginko biloba skin ageing (best for over the age of
50)
3 Green tea Phytosome Epigallocatachin from Thea
sinensis
50-100
mg
Nutraceutical, systemic antioxidnt.
Best for protection against cancer and
damage to cholesterol.
4 Centella Phytosome Terpenes - Used to treat vein and skin Disorders
5 Curcumin Phytosome Polyphenol form Curcuma 200- Cancer chemo preventive agent
longa 300mg
6 Ginseng Phytosome Ginsenosides from Panax
ginseng
150mg Immunomodulator
Phytosomes and its uses

CONCLUSION
 Phytosome forms a bridge between the conventional delivery system and novel
delivery system.
 Phytosome are advances form of herbal extract that are better absorbed which
results better than conventional herbal extract.
 Phytosomes have improved pharmacokinetic and pharmacological parameter, which
in result can advantantageously be used in various diseases.
 The nutraceutical product based on phytosome technology become present a the site
of action of liver, kidney, brain, heart at similar or less dose as compared to
conventional plant extract.
 Have a several excellent phenolic photo consultant have been successfully formulated
and delivery in this way exhibiting and remarkable therapeutic efficiency in animal as
well as in human models.
 Numerous phytosome product have been introduced and curing out applicable profit
to the pharmaceutical nutraceutical for cosmetic manufacture.surya prabhakar singh - phytosome

 Recent trend of phytosomes for delivering Herbal Extract with Improved
Bioavailability; volume 1 issue 4; 2012
 Review Article: Phytosome loaded Novel Herbal Drug Delivery system
21/06/2016
 Novel Apporach for herbal drug delivery2017
 Review article: Phytosomes is a novel drug delivery system based herbal
formulation 2/22/2018
 International Journal of Pharmaceutical Sciences and Drug
Research (www.ijpsdr.com)
Reference

Phytosome

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