Phytosome

PHYTOSOME

1. PHYTOSOME 1

2. Contents: Introduction Structure of phytosome Physical properties Structure of phytosome vs liposome Advantages Disadvantages Preparation of phytosome Evaluation Application Marketed products 2

3. Introduction: 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 phytoconstituents 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. 3

4. Structure of phytosome: 4

5. C hemical properties: 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. 5

6. Biological 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. 6

7. Structure of phytosome vs liposome: 7

8. 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. 8

9. Advantages: Enhanced absorption of herbal constituent. As the absorption of active constituents is improved, its dose requirement is also reduced. Phosphotidylcholine acts as hepatoprotective, giving synergistic effect. It shows better stability profile. It assures proper delivery of drugs to the respective tissues. Entrapment efficiency is high. Phyotosomes are also superior to liposomes in skin care products. Better bioavailability. Nutritional benefit. Enhanced permeation of drug through skin. 9

10. Disadvantages: When administered orally or topically they limit their bioavailability. Phytoconstituents is quickly eliminated from phytosome. Stability problem. 10

11. Different additives used in the formulation of phytosomes : phospholipids : soya phosphatidyl choline, egg phosphatidyl choline, dipalmityl phosphatidyl choline, phosphatidylcholine, phosphatidylethanolamine. 2) Aprotic solvent : Dioxane, acetone, methylene chloride. 3) Non-solvent : n-hexane. 4) Alcohol : ethanol, methanol. 11

12. Pr eparation of Phytosome: Phospholipid ↓ Dissolved in organic solvent containing drug extract ↓ Solution of phospholipid in organic solvent with drug extract ↓ Drying/ solvent evaporation ↓ Formation of thin film ↓ Hydration ↓ Formation of phytosomal suspension 12

13. Antisolvent 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 13

14. 2 ) Rotary evaporation technique: Drug and soya lecithin ↓ Dissolved in 30ml of tetrahydrofuran ↓ 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 14

15. 3) Solvent evaporation method : 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 15

16. Evaluation: Determination of entrapment efficiency:- the entrapment efficiency of a phytosomal formulation can be determined by subjecting the formulation to ultracentrifugation technique. Determination of vesicle size and zeta potential:- It can be determined by dynamic light scattering which uses a computerized inspection system and photon correlation spectroscopy. Surface tension activity measurement:- It can be measured by ring method using Du Nouy ring tensiometer. The surface tension of drug is measured. Spectroscopic evaluation:- it is employed in order to confirm the formation of complex as well as to study interactions between the two. The method include H’NMR, 13 C NMR, and FTIR. 16

17. 5) Determination of drug content:- drug content of phytosome complex was determined by dissolving 100mg of complex in 10ml of methanol. After dilution, absorbance was determined by UV spectrophotometer at 269nm. 6 ) In-vitro and In-vivo evaluation:- this can be done according to therapeutic activity measurement parameters of biologically active phytoconstituents present in phytosomes . 17

18. Applications: 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 bile duct. 18

19. 2) 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. 3) Phytosome of green tea: Green tea leaves is characterized by presence of polyphenolic compound epigallocatechin-3-0-gallate as the key component. These are potent modulator of several biochemical process linked to the breakdown of homeostasis in major chronic degenerative diseases like cancer and atherosclerosis. It has also beneficial activities like antioxidant, anticarcinogenic, antimutagenic, cardio protective effects. 19

20. 4) 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 deviation of action. 20

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22. -used for healthy joints. 22

23. Reference: Semalty A, Semalty M, Singh R, Rawat MSM. Phytosomes in herbal drug delivery. Indian drugs 2006; page no: 937-946. Zhang J, Tang Q, Xu X, Li N. Development and evaluation of a novel phytosome -loaded chitosan microsphere system for curcumin delivery. International Journal of Pharmaceutics 2013; 448:168– 174. 14. Habbu P, Madagundi S, Kulkarni R, Jadav S, Vanakudri R, Kulkarni V, et al. Preparation and evaluation of Bacopa phospholipids complex for antiamnesic activity in rodents. Drug invention today 2013; 5(1): 13 - 21. Parris K, Kathleen H, A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybinphosphatidylcholine complex, Altern Med Rev, 10(3), 2005, 193-203. Gupta A, Ashawat MS, Saraf S, Phytosome: A novel approach towards functional cosmetics, J Plant sci, 2(6), 2007, 644-649. 23

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