Phytosome

phytosome,niosome

1. Submitted by:- Surya prabhakar singh M. Pharma 2 nd 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

2. 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 surya prabhakar singh - phytosome

3. 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 b ecause of their water soluble property and lipophilic outer layer it shows better absorption and produce better bioavailability . INTRODUCTION surya prabhakar singh - phytosome

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5. 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 surya prabhakar singh - phytosome

6. 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 ? surya prabhakar singh - phytosome

7. 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 . surya prabhakar singh - phytosome

8. 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 surya prabhakar singh - phytosome

9. 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 μ m. STRUCTURE OF PHYTOSOME surya prabhakar singh - phytosome

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11. 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 surya prabhakar singh - phytosome

12. 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. surya prabhakar singh - phytosome

13. PYTOSOME VS LIPOSOME surya prabhakar singh - phytosome

14. 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

15. 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 surya prabhakar singh - phytosome

16. 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 surya prabhakar singh - phytosome

17. 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 chemical bonds 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 surya prabhakar singh - phytosome

18. 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 herbal constituent, 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, and thus can be used for systemic targeting. surya prabhakar singh - phytosome

19. 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 surya prabhakar singh - phytosome

20. 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 surya prabhakar singh - phytosome

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23. 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 surya prabhakar singh - phytosome

24. 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 surya prabhakar singh - phytosome

25. Phospholipids Solution of phospholipidsin organic solvent with drug extract Drying COMMON STAGE OF PREPARATION surya prabhakar singh - phytosome

26. Formation of thin film Hydration Formation of phytosomal suspension surya prabhakar singh - phytosome

27. 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. surya prabhakar singh - phytosome

28. 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: surya prabhakar singh - phytosome

29. • 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 surya prabhakar singh - phytosome

30. 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: surya prabhakar singh - phytosome

31. 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 surya prabhakar singh - phytosome

32. 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:- surya prabhakar singh - phytosome

33. Can be formulated – orally Topically The formulation tips shown here- FORMULATION Soft gelatin capsule Topical dosage form Hard geltin capcule surya prabhakar singh - phytosome

34. 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 surya prabhakar singh - phytosome

35. 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: surya prabhakar singh - phytosome

36. 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 surya prabhakar singh - phytosome

37. 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: surya prabhakar singh - phytosome

38.  Particle size  Entrapment Efficiency  FTIR Spectrographic Analysis  Differential Scanning Calorimetry (DSC)  Drug content  Scanning Electron Microscopy  Stability study Evaluation of phytosomes surya prabhakar singh - phytosome

39. 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) surya prabhakar singh - phytosome

40. 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 Spectrographic Analysis surya prabhakar singh - phytosome

41. 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) surya prabhakar singh - phytosome

42. 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, 10000 and 30000X magnifications surya prabhakar singh - phytosome

43. 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. surya prabhakar singh - phytosome

44. 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 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 defense of plasma. surya prabhakar singh - phytosome

45. 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 surya prabhakar singh - phytosome

46. 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. surya prabhakar singh - phytosome

47. 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 surya prabhakar singh - phytosome

48. 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. H ave 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. N umerous phytosome product have been introduced and curing out applicable profit to the pharmaceutical nutraceutical for cosmetic manufacture. surya prabhakar singh - phytosome

49. 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 delivery 2017 Review article: Phytosomes is a novel drug delivery system based herbal formulation 2/22/2018 Int e r na t ional J ou r na l o f P ha r ma c e u ti c a l Sciences and Drug Research ( www.ijpsdr.com ) Reference surya prabhakar singh - phytosome

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