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PHYTOSOMES
Dr. Anil Pethe
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management,
SVKM’S NMIMS, Mumbai
Introduction
Structure
Phytosomes Vs. Liposome
Advantages & Disadvantages
Properties of phytosomes
Applications
Marketed products
Contents
• Phytosome is novel drug delivery system is a patented technology (U.S. Patent
#4,764,508) that combines hydrophilic bioactive phyto-constituents of herbs/
herbal extracts and bound by phospholipids.(soybean phospholipids ,lecithin)
• More bioavailable than a simple/convential herbal extract due to its enhanced
capacity to cross the lipid rich bio-membranes and reach circulation.
• As they are better absorbed and produces better results
• Applied to standardized plant extracts, water soluble phyto-constituents and
many popular herbal extracts including , grape seed, hawthorn, olive fruits
and leaves, milk thistle, green tea, ginseng etc into phospholipids to produce
lipid compatible molecular complex
Introduction
• Phytosome structures contain the active ingredients of the herb
surrounded by the phospholipids.
• The presence of a surfactant i.e. the phospholipids in the
molecule these 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
• Example-PC is a bifunctional compound. Specifically the choline
head (hydrophilic) binds to these compounds while the
phosphatidyl portion (lipophilic) comprising the body and tail
which then envelopes the choline bound material and forms
phyto-phospholipid complex.
• Molecules are anchored through chemical bonds to the polar
choline head of the PC, it can be demonstrated by specific
spectroscopic techniques.
Structure of Phytosomes
Phytosomes Vs. Liposome
Phytosomes Liposomes
In phytosome, the
phosphatidylcholine
and the plant components
actually form a 1:1 or a 2:1
molecular complex depending on
the substance(s) complexes.
A liposome is formed by mixing
a water soluble substance with
phosphatidylcholine in definite
ratio under specific conditions.
Phytosome involves chemical
bonds.
Here, no chemical bond is
formed; the phosphatidylcholine
molecules surround the water
soluble substance.
Phytosome are much better
absorbed than liposomes
showing better bioavailability.
Bioavailability of liposomes is
less than phytosomes.
• It enhances the absorption of lipid insoluble polar phytoconstituents through oral as well
as topical route showing better bioavailability, hence significantly greater therapeutic
benefit.
• As the absorption of active constituent(s) is improved, its dose requirement is also
reduced.
• Phosphatidylcholine used in preparation of phytosomes, besides acting as a carrier also
acts as a hepatoprotective, hence giving the synergistic effect when hepatoprotective
substances are employed.
• Chemical bonds are formed between phosphatidylcholine molecule and phytoconstituent,
so the phytosomes show better stability profile.
• Added nutritional benefit of phospholipids.
Advantages
• It assures proper delivery of drug to the respective tissues.
• The nutrient safety of the herbal extracts need not be compromised by
conveying the herbal drug as means of phytosomes.
• Entrapment efficiency is high and more over predetermined because
drug itself is in conjugation with lipids in forming vesicles.
• There is no problem in drug entrapment while formulating phytosomes.
• Phytosomes are also superior to liposomes in skin care products.
Advantages (cont.)
1. Chemical Properties
• Phytosomes is a complex between a natural product and natural
phospholipids.
• The phytosome complex is obtained by reaction of suitable amounts of
phospholipid and the substrate in an appropriate solvent such as
glycerol.
• The main phospholipid-substrate interaction is due to the formation of
hydrogen bonds between the polar head of phospholipids (i.e.
phosphate and ammonium groups) and the polar functionalities of the
substrate.
• When treated with water, phytosomes assumes a micellar shape forming
liposomial-like structures.
Properties of Phytosomes
2. Biological Properties
• Phytosome are advanced forms of herbal products that are better absorbed,
utilized and as a result produce better results than conventional herbal extracts.
• Phytosomes are lipophilic substances with definite melting point, freely soluble
in non-polar solvents, and moderately soluble in fats.
• 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.
Properties of Phytosomes (cont.)
Method of preparation of Phytosomes
Particle Size and Size Distribution
• The particle size and size distribution of Phytosome were determined by Malvern Zetasizer based
on laser light scattering principle. A Malvern laser light scattering Zetasizer equipped with an Argon
laser was used for evaluating the particle size & particle size diameter.
Scanning Electron Microscopy (SEM)
• Scanning electron microscopy of the optimized Phytosomal suspension was performed for
determining the surface morphology, size and shape of formulation.
Entrapment Efficiency
• Entrapment efficiency of phytosomal vesicles was determined by centrifugation method. The
vesicles were separated in a high speed cooling centrifuge (REMI ultra-centrifugation) at 10,000
rpm for 90 minutes at a temperature maintained at 4ºC. Theoretical drug loading was determined
by calculation assuming that the entire drug present in the phospholipid used gets entrapped in
phytosomes and no loss occurs at any stage of preparation of phytosomes.
• Practical drug loading was determined by tacking a 10ml of phytosomal suspension was taken in
centrifuge tube. The sediment and supernatant were separated. Sediment was dissolved in
methanol which was then estimated for drug content. The absorbance of the drug was noted by
UV analysis.
In-vitro drug release
• The in-vitro release study of from the phytosomal suspension was studied by using a Franz
diffusion cell.
Evaluation of Phytosomes
Silymarin Phytosome
• Most of the phytosomes are focused to Silybum marianum which contains premier
liver-protectant flavonoids.
• The fruit of the milk thistle plant (S. marianum, Family Steraceae) contains
flavonoids known for hepato-protective effects.
• Silymarin has been shown to have positive effects in treating liver diseases of
various kinds, including hepatitis, cirrhosis, fatty infiltration of the liver (chemical
and alcohol induced fatty liver) and inflammation of the bile duct.
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 defences of plasma.
Application of phytosome
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.
Phytosomes of curcumin
• Maiti et al. developed the phytosomes of curcumin (flavonoid from turmeric,
Curcuma longa linn) and naringenin (flavonoid from grape, Vitis vinifera).
• Phytosome of naringenin produced better antioxidant activity than the free
compound with a prolonged duration of action
Application of phytosome
Marketed phytosome

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Phytosomes

  • 1. 1 PHYTOSOMES Dr. Anil Pethe Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’S NMIMS, Mumbai
  • 2. Introduction Structure Phytosomes Vs. Liposome Advantages & Disadvantages Properties of phytosomes Applications Marketed products Contents
  • 3. • Phytosome is novel drug delivery system is a patented technology (U.S. Patent #4,764,508) that combines hydrophilic bioactive phyto-constituents of herbs/ herbal extracts and bound by phospholipids.(soybean phospholipids ,lecithin) • More bioavailable than a simple/convential herbal extract due to its enhanced capacity to cross the lipid rich bio-membranes and reach circulation. • As they are better absorbed and produces better results • Applied to standardized plant extracts, water soluble phyto-constituents and many popular herbal extracts including , grape seed, hawthorn, olive fruits and leaves, milk thistle, green tea, ginseng etc into phospholipids to produce lipid compatible molecular complex Introduction
  • 4. • Phytosome structures contain the active ingredients of the herb surrounded by the phospholipids. • The presence of a surfactant i.e. the phospholipids in the molecule these 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 • Example-PC is a bifunctional compound. Specifically the choline head (hydrophilic) binds to these compounds while the phosphatidyl portion (lipophilic) comprising the body and tail which then envelopes the choline bound material and forms phyto-phospholipid complex. • Molecules are anchored through chemical bonds to the polar choline head of the PC, it can be demonstrated by specific spectroscopic techniques. Structure of Phytosomes
  • 5. Phytosomes Vs. Liposome Phytosomes Liposomes In phytosome, the phosphatidylcholine and the plant components actually form a 1:1 or a 2:1 molecular complex depending on the substance(s) complexes. A liposome is formed by mixing a water soluble substance with phosphatidylcholine in definite ratio under specific conditions. Phytosome involves chemical bonds. Here, no chemical bond is formed; the phosphatidylcholine molecules surround the water soluble substance. Phytosome are much better absorbed than liposomes showing better bioavailability. Bioavailability of liposomes is less than phytosomes.
  • 6. • It enhances the absorption of lipid insoluble polar phytoconstituents through oral as well as topical route showing better bioavailability, hence significantly greater therapeutic benefit. • As the absorption of active constituent(s) is improved, its dose requirement is also reduced. • Phosphatidylcholine used in preparation of phytosomes, besides acting as a carrier also acts as a hepatoprotective, hence giving the synergistic effect when hepatoprotective substances are employed. • Chemical bonds are formed between phosphatidylcholine molecule and phytoconstituent, so the phytosomes show better stability profile. • Added nutritional benefit of phospholipids. Advantages
  • 7. • It assures proper delivery of drug to the respective tissues. • The nutrient safety of the herbal extracts need not be compromised by conveying the herbal drug as means of phytosomes. • Entrapment efficiency is high and more over predetermined because drug itself is in conjugation with lipids in forming vesicles. • There is no problem in drug entrapment while formulating phytosomes. • Phytosomes are also superior to liposomes in skin care products. Advantages (cont.)
  • 8. 1. Chemical Properties • Phytosomes is a complex between a natural product and natural phospholipids. • The phytosome complex is obtained by reaction of suitable amounts of phospholipid and the substrate in an appropriate solvent such as glycerol. • The main phospholipid-substrate interaction is due to the formation of hydrogen bonds between the polar head of phospholipids (i.e. phosphate and ammonium groups) and the polar functionalities of the substrate. • When treated with water, phytosomes assumes a micellar shape forming liposomial-like structures. Properties of Phytosomes
  • 9. 2. Biological Properties • Phytosome are advanced forms of herbal products that are better absorbed, utilized and as a result produce better results than conventional herbal extracts. • Phytosomes are lipophilic substances with definite melting point, freely soluble in non-polar solvents, and moderately soluble in fats. • 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. Properties of Phytosomes (cont.)
  • 10. Method of preparation of Phytosomes
  • 11. Particle Size and Size Distribution • The particle size and size distribution of Phytosome were determined by Malvern Zetasizer based on laser light scattering principle. A Malvern laser light scattering Zetasizer equipped with an Argon laser was used for evaluating the particle size & particle size diameter. Scanning Electron Microscopy (SEM) • Scanning electron microscopy of the optimized Phytosomal suspension was performed for determining the surface morphology, size and shape of formulation. Entrapment Efficiency • Entrapment efficiency of phytosomal vesicles was determined by centrifugation method. The vesicles were separated in a high speed cooling centrifuge (REMI ultra-centrifugation) at 10,000 rpm for 90 minutes at a temperature maintained at 4ºC. Theoretical drug loading was determined by calculation assuming that the entire drug present in the phospholipid used gets entrapped in phytosomes and no loss occurs at any stage of preparation of phytosomes. • Practical drug loading was determined by tacking a 10ml of phytosomal suspension was taken in centrifuge tube. The sediment and supernatant were separated. Sediment was dissolved in methanol which was then estimated for drug content. The absorbance of the drug was noted by UV analysis. In-vitro drug release • The in-vitro release study of from the phytosomal suspension was studied by using a Franz diffusion cell. Evaluation of Phytosomes
  • 12. Silymarin Phytosome • Most of the phytosomes are focused to Silybum marianum which contains premier liver-protectant flavonoids. • The fruit of the milk thistle plant (S. marianum, Family Steraceae) contains flavonoids known for hepato-protective effects. • Silymarin has been shown to have positive effects in treating liver diseases of various kinds, including hepatitis, cirrhosis, fatty infiltration of the liver (chemical and alcohol induced fatty liver) and inflammation of the bile duct. 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 defences of plasma. Application of phytosome
  • 13. 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. Phytosomes of curcumin • Maiti et al. developed the phytosomes of curcumin (flavonoid from turmeric, Curcuma longa linn) and naringenin (flavonoid from grape, Vitis vinifera). • Phytosome of naringenin produced better antioxidant activity than the free compound with a prolonged duration of action Application of phytosome