NDDS in herbal drugs

1. PHYTOSOMES

2. INTRODUCTION
• The term ‘Phyto’ means plant while ‘Some’ means cell-
like. Phytosome is novel drug delivery system that
combines hydrophilic bioactive phyto constituents of
herbs/ herbal extracts and bound by phospholipids.
• More bioavailable than a simple/conventional herbal
extract due to its enhanced capacity to cross the lipid
rich bio membranes and reach circulation.
• As they are better absorbed they produce better results
• Applied to standardized plant extracts, water soluble
phyto constituents and many popular herbal extracts
including , grape seed, olive fruits and leaves, green
tea, ginseng etc into phospholipids to produce lipid
compatible molecular complexes

3. • The presence of a surfactant i.e. the phospholipids in the molecule these are
shielded from water-triggered degradation .
• Molecules are anchored through chemical bonds to the polar choline
head, it can be demonstrated by specific spectroscopic techniques.
Introduction (contd.)

4. ADVANTAGES
Marked enhancement of bioavailability.
Valuable components of the herbal extracts are protected from destruction
by digestive secretions and gut bacteria
No compromise of nutrient safety.
Dose requirement is reduced due to absorption of chief constituent.
Phytosomes shows better stability profile because chemical bonds are
formed between phospholipid molecules and phytoconstituent
Phospholipid used in the phytosome process besides acting as a carrier also
nourishes the skin, because it is essential part of cell membrane.

5.  Low risk profile: This technology has no large-scale drug development risk
since the toxicological profiles of the phytosomal components are well
documented in the scientific literatures.
 Relatively simple to manufacture with no complicated technical investment
required for the production of Phytosomes.
 They permeate the non-lipophilic botanical extract to allow better
absorption from the intestinal lumen, which is otherwise not possible
DISADVANTAGE
• Phytoconstituent is quickly eradicated/ eliminated from phytosome.
Advantages (contd.)

6. Properties of Phytosomes
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.

7. 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.

8. PREPRATION METHOD
Solvent Evaporation method is the most common technique used for the
preparation of phytosomes
Phytosomes are prepared by reacting natural or synthetic phospholipids
with active components like bioflavonoid, flavolignan and polyphenolic
constituents.
• Phospholipid dissolve in organic solvent
• Solution of phospholipid in solution containing Organic solvent + Herbal
extract
• Drying
• Thin Film Formation
• Hydration of thin film
• Formation of phytosome complex (suspension)
• Isolation by precipitation with non solvent (such as aliphatic hydrocarbons)
• Drying (By lyophilization or spray drying)

9. EVALUATION
 Transition temperature:
The transition temperature of the vesicular lipid system can be settled
via differential scanning calorimetry
.
 Entrapment efficiency:
The entrapment efficiency of a phytosomal preparation can be
determined by exposing the preparation to ultracentrifugation
method.
 Vesicle size and zeta potential:
The particle size and zeta potential of phytosomes can be confirmed
by dynamic light scattering, which usages a computerized
examination system and photon correlation spectroscopy.
 Surface tension activity measurement:
The surface tension activity of the drug in aqueous solution can be
determined by the Du Nouy ring tensiometer.

10. Visualization:
Visualization of phytosomes can be accomplished using scanning
electron microscopy (SEM) and by transmission electron microscopy.
 Vesicle stability:
The steadiness of vesicles can be measured by calculating the size and
structure of the vesicles over time. The mean size is calculated by DLS
and structural changes are monitored by tem.
 Spectroscopic evaluation
To confirm the formation of a complex or to study the reciprocal
interaction between the phyto-constituents and the phospholipid H1
NMR, C13 NMR, FTIR are used
 In vitro and In vivo evaluations
Models of in-vitro and in-vivo evaluations are selected on the basis of
the expected therapeutic activity of biologically active
phytoconstituents present in the phytosome.
Evaluation (contd.)

11. Difference between Liposome and
phytosome
Sl no Phytosome Liposome
1 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.
2 Phytosome involves chemical bonds. Here, no chemical bond is formed; the
phosphatidylcholine molecules surround
the water soluble substance.
3 Phytosome are much better absorbed than
liposomes showing better bioavailability.
Bioavailability of liposomes is less
than phytosomes.

12. Structure difference between phytosome and liposome

13. APPLICATION 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. Silymarin
Phytosome
• 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 defenses of plasma.

14. Application (contd.)
• Phytosome of green tea
• Green tea leaves (Thea sinensis) 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, cardio
protective effects.
• Phytosomes of curcumin
• 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

15. Sr. No. Trade name Phytoconstituents complex Indications
1 Silybin phytosome Silybin from Silibium marianum Hepatoprotective
, Antioxidant.
2 Grape seed
(Leucoselect) phytosome
Procyanidins from vitis vinifera Antioxidant
,
Anticancer.
3 Ginseng phytosome Ginsenosides from Panax ginseng Immunomodulator
4 Hawthorn phytosome Flavonoids from Crataegus species Antihypertensive,
Cardioprotective
.
5 Sericoside phytosome Sericoside from Terminalia sericea Skin improver,
Anti-
Wrinkles
6 Ginko select phytosome Flavonoids from Ginko biloba Anti
aging,Protects
Brain and
Vascular liling
7 Olea select phytosome Polyphenols from Olea europea Anti–hyperlipidemic,
Anti-inflammatory
8 Green select phytosome
macy, ADTU
Epigallocatechin from Thea sinensis Anti-cancer,
Antioxidant