Phytosome preparation characterisation application

1. PHYTOSOMES
Department of Pharmaceutical Sciences,
R.T.M.N.U, Nagpur - 440033
By Ashish R. Agrawal
Mpharm Pharmaceutics 1ST year 2018-2019

2. CONTENTS
• INTRODUCTION
• PHYTOSOME
• ADVANTAGES
• PHYTOSOME VS LIPOSOME
• BIOAVAILABILITY
• PHYSICAL AND CHEMICAL PROPERTIES
• PREPARATION
• CHARACTERIZATION
• FORMULATION
• MARKETED PRODUCTS

3. INNOVATOR COMPANY
• INDENA Phytosome® U.S. Patent # 4,764,508
worlds leading company in the identification, development
and production of active principles derived from plants, for
use in pharmaceutical, health-food and personal care
industry.

5. INTRODUCTION
• Polyphenolics and terpenes are ubiquitous in plants,
but their poor solubility and hydrolytical instability in water
and organic solvents at physiological pH values make them
very poorly absorbed both orally and topically.
• Bioavailability can be improved by using new
delivery systems which can enhance the rate and the extent of
solubilization into aqueous intestinal fluids and the capacity to
cross biomembranes.
• It is claimed that phytosome increases absorption of
"conventional herbal extracts" or isolated active principles both
topicallyas well as orally.

6. • Polyphenolics exhibit a marked affinity for phospholipids
via hydrogen bondings and dipolar
interactions with the charged phosphates groups of
phospholipids.
• By complexing the polyphenolic phytoconstituents in a
definite ratio with phosphatidylcholine, Indena has
developed a new series of non-covalent supramolecular
adducts named “Phytosome®”.

7. PHYTOSOME
• A phytosome is a complex of a natural active ingredient and
a phospholipid - mostly lecithin
• Phytosomes are novel drug delivery system containing
hydrophilic bioactive phytoconstituents of herbs surround
and bound by phospholipids.

8. ADVANTAGES
• Enhanced absorption of herbal constituent.
• Better bioavailability.
• Reduced dose.
• Facilitates liver targeting by delivering liver protecting flavonoids.
• Phosphatidylcholine acts as a hepatoprotective. i.e.
Hepatoprotective synergistic effect.
• Better stability profile.
• Nutritional benefit.
• Entrapment efficiency is high
• This technology offers cost effective delivery of phytoconstituents.
• enhanced permeation of drug through skin

9. PHYTOSOME VS LIPOSOME
• Furthermore, in liposomes the content of phospholipids is
much higher, about five times the one in Phytosome®, making
this delivery form not suitable for oral clinical realistic dosages
for natural compounds.
PHYTOSOME LIPOSOME
It is a solid dispersion of an extract in a
dietary phospholipid matrix (non GMO
lecithin from soy), the ingredient can
somehow be compared to an integral
part of the lipid membrane.
The ingredients are dissolved in the
central part of the cavity, with limited
possibility of molecular interaction
between the surrounding lipid and a
hydrophilic substance.
Ratio of phosphatidylcholine to
phytoconstituents is 1:1 or 2:1 ,
depending on the phytoconstituents.
Thousand of phosphatidylcholine
molecules surrounds the water soluble
molecules.

10. LIPOSOME
PHYTOSOME
The Phytosome® formulation also increases the absorption of active
ingredients when topically applied on the skin, and improves systemic
bioavailability when administered orally. In water medium, a
Phytosome® will assume a micellar shape, forming a spherical
structure, overall similar to a liposome, but with a different guest
localization.

11. BIOAVAILABILITY
• Bioavailability is one of the essential tools in pharmacokinetics. When an
ingredient is administered orally, its bioavailability is generally limited
due to incomplete absorption and first-pass metabolism or may vary
from patient to patient.
• Compared to unformulated ingredients, with the Phytosome® approach
the bioavailability of the ingredients is improved, without resorting to
pharmacological adjuvants or structural modification, but by
formulating them with a dietary ingredient.

12. PHYSICAL & CHEMICAL PROPERTIES
• It is lipophilic substance with a definite melting point
• Freely soluble in nonpolar and aprotic solvent
solvents in which the hydrophilic moiety is not.
• Moderately soluble in fats.
• Insoluble in water.
• When treated with water, they assume a micelle
shape, forming structures which resemble liposome.

13. SPECTRA
• In 1H-NMR spectrum  The signal of complexed substance
undergo a strong broadening so as they can no more be
evidenced in the spectra.
• In 13C-NMR spectrum The signal of the complexed as well
as those of the choline & glycerin portion of phospholipid can
no more be recorded.
 The phosphorous nucleus itself undergoes a band
broadening which indicates that it is involved in complex
formation.
• In both spectrum  Only the lipid chain signals appear,
because they are free to rotate & give complex its lipophilic
character.

14. PREPARATION OF PHYTOSOME
Phospholipid
Dissolved in organic solvent containing drug/extract
Hydration
Solution of phospholipid in organic solvent with drug/extract
Drying / Solvent Evaporation
Formation of thin film
Formation of phytosomal suspension

15. Different additives used in the formulations of Phytosomes:
1. Phospholipids: Soya phosphatidyl choline, Egg phosphatidyl
choline , Dipalmityl phosphatidyl choline, Distearyl
phosphatidyl choline , Phosphotidylcholine ,
Phosphotidylethanolamine, Phosphotidylserine.
2. Aprotic solvent: Dioxane, acetone, methylene chloride
3. Non solvent: n-hexane and non solvent i.e. aliphatic
hydrocarbon
4. Alcohol: Ethanol, Methanol

16. 1)Antisolvent precipitation technique
Drug + Soya Lecitin
Reflux With 20ml Dichloromethane At
60ºc For 2 Hr.
Concentrate Mixture To 5-10ml
Add Hexane 20ml
Filter The Ppt Formed Dry ,Crush
And Pass Through #100

17. 2)Rotary evaporation technique
Drug And Soya Lecithin
Dissolved In 30 ml Of Tetrahydrofuran
Stirring For 3 Hours At A Temperature Not Exceeding 40ºc
Thin Film Is Formed
Add n-Hexane With Stirring
Precipitate Obtained
Dry And Pass Through Mesh
Phytosomes Formed

18. 3) Solvent evaporation method
Drug And Soya Lecithin
Refluxed With 20 ml Of Acetone at a Temperature 50 -
60ºc For 2 hr
Concentrated Mixture To 5-10 ml
Obtain The Precipitate
Filter And Collect
Phytosomes Obtained

19. CHARACTERIZATION OF
PHYTOSOME
• Physical size
• Membrane permeability
• Percent entrapped solute
• Chemical composition as well as quality and purity of the
starting material
• Visualization
a) Transmission electron microscopy(TEM)
b) Scanning electron microscopy(SEM)
• Spectroscopic evaluation
a) FTIR
b) 1H-NMR
c) 13C-NMR

20. FORMULATION
Tablet formulation with Phytosome® complex
Leucoselect® Phytosome® 100.0 mg
Soy polysaccharides 138.0 mg
Corn starch 100.0 mg
Silicon dioxide 6.0 mg
Talc 3.0 mg
Magnesium stearate 3.0 mg

21. Hard gelatin capsule formulation with Phytosome®
complex
Ginkgoselect® Phytosome® 180.0 mg
Dicalcium phosphate dihydrate 196.0 mg
Microcrystalline cellulose 47.0 mg
Croscarmellose sodium 23.0 mg
Talc 2.0 mg
Magnesium stearate 2.0 mg

22. Soft gelatin capsules
Ginkgoselect ® Phytosome® 180 mg
Soy bean oil 250 mg
Soy lecithin q.S
Glycerylmonostearate q.S

23. Commercially available Phytosome
Phytosome Herbal drug Indication
Ginkgoselect ® ginkgobiloba Improve memory,
Brain function,
Anti inflammatory agent
Silybin® Silybum marianum Anti oxidant,
Anti aging,
Hepatoprotective
Hawthore® Crataegus oxyacantha Help to strengthen heart
and cardiovascular
system
Ginselect® Panax ginseng Promote adaptogenic
functions and resistance
to stress
Curcumin Curcuma longa Chemoprotective agent
Grapseed Grapseed Natural antioxidant
protectant
Greenselect® Camellia sinensis Antioxidant,
Cardioprotective,
Food product