Phytosome: A Novel Dosage Structure

Dubey Darshan

Phytosome are created when the standardized extract and active ingredients of an herb are bound to the phospholipids on a molecular level. Phytosome structures contain the active ingredients of the herb surrounded by the phospholipids.

The phospholipid molecular structure includes a water-soluble head and two fat-soluble tails, because of this dual solubility, the phospholipid acts as an effective emulsifier, which is also one of the chief components of the membranes in our cells. Phytosomes are advanced forms of herbal products that are better absorbed, utilized, and as a result produce better results than conventional herbal extracts.

Introduction

Preparations of plants or parts of them were widely used in popular medicine since ancient times and till today the use of phytomedicines is widespread in most of the world’s population. During the last century chemical and pharmacological studies have been performed on a lot of plant extracts in order to know their chemical composition and confirm the indications of traditional medicine. The Phytosome process produces a little cell because of that the valuable components of the herbal extract are protected from destruction by digestive secretions and gut bacteria. 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 ¹ , finally reaching the blood. Most of the bioactive constituents of phytomedicines are flavonoids (e.g., anthocyanidins from bilberry, catechins from green tea, silymarin from milk thistle). However, many flavonoids are poorly absorbed the poor absorption of flavonoid nutrients is likely due to two factors. First, they are having multiple-ring molecules that are too large to be absorbed by simple diffusion.Secondly flavonoid molecules typically have poor miscibility with oils and other lipids, which limited their ability to pass across the lipid-rich outer membranes of the enterocytes of the small intestine. Water-soluble flavonoid molecules can be converted into lipid-compatible molecular complexes, aptly called phytosomes.The lipid-phase substances employed to make flavonoids lipid-compatible are phospholipids from soy, mainly phosphatidylcholine(PC). Phosphatidylcholine is  the principal molecular building block of cell membranes miscible both in water and in oil environments, and is well absorbed when taken by mouth. Chemical analysis indicates that in phytosome is usually a flavonoid molecule linked with at least one phosphatidylcholine molecule. A bond is formed between these two molecules, creating a hybrid molecule. This highly lipid-miscible hybrid bond is better suited to merge into the lipid phase of the enterocyte's outer cell membrane. Phosphatidylcholine is not merely a passive "carrier" for the bioactive flavonoids of the phytosomes, but is itself a bioactive nutrient with documented clinical efficacy for liver disease, including alcoholic hepatic steatosis, drug-induced liver damage, and hepatitis. The intakes of phytosome preparations sufficient to provide reliable clinical benefit often also provide substantial phosphatidylcholine intakes. The phytosome process has been applied to many popular herbal extracts including Ginkgo biloba, grape seed, hawthorn, milk thistle, green tea, and ginseng . The flavonoid and terpenoid components of these herbal extracts lend themselves quite well for the direct binding to phosphatidylcholine. Specifically, the choline head of the phosphatidylcholine molecule binds to these compounds while the fat-soluble phosphatidyl portion comprising the body and tail then envelopes the choline-bound material. The result is a little micro sphere or cell is produced ² . Phytosomes have improved pharmacokinetic and pharmacological parameter which in result can advantogenously be used in the treatment of the acute and chronic liver disease of toxic metabolic or infective origin or of degenerative nature. It can also be used in anti-inflammatory activity as well as in pharmaceutical and cosmetic compositions ² .

Preparation of Phytosome

Phytosomes are novel complexes which are prepared by reacting from 3-2 moles but preferably with one mole of a natural or synthetic phospholipid, such as phosphatidylcholine, phosphatidylethanolamine or phosphatidyiserine with one mole of component for example- flavolignanans, either alone or in the natural mixture in aprotic solvent such as- dioxane or acetone from which complex can be isolated by precipitation with non solvent such as aliphatic hydrocarbons or lyophilization or by spary drying. In the complex formation of phytosomes the ratio between these two moieties is in the range from 0.5-2.0 moles. The most preferable ratio of phospholipid to flavonoids is 1:1 ³ .

 In the phytosome preparations, phospholipids are selected from the group consisting of soy lecithin, from bovine or swine brain or dermis, phosphatidylcholine, phosphatidylethanolamine, phosphatidyiserine in which acyl group may be same or different and mostly derived from palmitic, stearic, oleic and linoleic acid. Selection of flavonoids are done from the group consisting of quercetin, kaempferol, quercretin-3, rhamnoglucoside, quercetin-3-rhamnoside, hyperoside, vitexine, diosmine, 3- rhamnoside, (+) catechin, (-) epicatechin, apigenin-7-glucoside, luteolin, luteolinglucoside, ginkgonetine, isoginkgonetine and bilobetine. Some liposomal drugs complex operate in the presence of the water or buffer solution where as phytosomes operate with the solvent having a reduced dielectric constant. Starting material of component like flavonoids are insoluble in chloroform, ethyl ether or benzene. They become extremely soluble in these solvents after forming phytosomes. This chemical and physical property change is due to the formation of a true stable complex ⁴ .

Properties of Phytosomes

1-Chemical properties:

Phytosomes is a complex between a natural product and natural phospholipids, like soy phospholipids. Such a complex is obtained by reaction of stoichiometric amounts of phospholipid and the substrate in an appropriate solvent. On the basis of spectroscopic data it has been shown that 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, In liposomes the active principle is dissolved in the internal pocket or it is floating in the layer membrane, while in phytosomes the active principle is anchored to the polar head of phospholipids, becoming an integral part of the membrane for example in the case of the catechindistearoylphosphatidylcholine complex, in this there is the formation of H-bonds between the phenolic hydroxyls of the flavone moiety and the phosphate ion on the phosphatidylcholine side.

Phosphatidylcholine                              

This can be deduced from the comparison of the NMR of the complex with those of the pure precursors. The signals of the fatty chain are almost unchanged. Such evidences inferred that the two long aliphatics chains are wrapped around the active principle, producing a lipophilic envelope, which shields the polar head of the phospholipid and the catechin ⁵ . 

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 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 ⁶ .

Characterization of Phytosomes

The behavior of phytosomes in both physical and biological system is governed by the factors such as physical size membrane permeability; percent entrapped solutes, chemical composition as well as the quantity and purity of the starting materials. Therefore, the phytosomes are characterized for physical attributes i.e. shape, size, its distribution, percentage drug capture entrapped volume, percentage drug released and chemical composition ⁷ .

Difference between Phytosome and liposome

Fig no. 1

Liposomes are used primarily in cosmetics to deliver water-soluble substances to the skin. Mixing a water-soluble substance with phosphatidylcholine forms a liposome. No chemical bond is formed and there may be hundreds or even thousands of phosphatidylcholine molecules surrounding the water-soluble compound. In contrast, with the Phytosome process the phosphatidylcholine and the individual plant components actually from a 1:1 or a 2:1 complex depending on the substance ⁸ . Phytosomes are not liposomes - structurally, the two are distinctly different as shown in fig. no.1. The phytosome is a unit of a few molecules this makes difference so the phytosomes being much better absorbed that liposomes. Not surprisingly, Phytosomes are also superior to liposomes in skin care products while the liposome is an aggregate of many phospholipid molecules that can enclose other phytoactive molecules but without specifically bonding to them. Liposomes are touted delivery vehicles, but for dietary supplements their promise has not been fulfilled. But for phytosome products numerous studies prove they are markedly better absorbed and have substantially greater clinical efficacy. Companies have successfully applied this technology to a number of standardized flavonoid preparations. The phytosomes technology is a breakthrough model for ⁹ :

· Marked enhancement of bioavailability

· Significantly greater clinical benefit

· Assured delivery to the tissues

· No compromise of nutrient safety

Advantages over the conventional dosage form

The various advantages of phytosome are mentioned below;

• Phytosome are better bioavailable botanical extracts, dramatically enhance bioavailablity due to their complex with phospholipids and delivers faster and improved absorption in intestinal tract ¹⁰ .
• Phytosome permeates the non-lipophillic botanical extract to be better absorbed in intestinal lumen ¹¹ .
• Phytosome will be given in small quantity and desired results can be achieved.
• Phytosome are widely used in cosmetics due to there more skin penetration and have a high lipid profile.
• Phytosome are been used to give liver protectant flavonoids because they were easily bioavailable.

Discussion

Phytosomes are complex compounds of flavonoids with phospholipids, characterized by high lipophillic and improved bioavailibility and therapeutic properties as compare with free, not complex flavonoids. Phytosomes are produced by a patent process in which individual component of herbal extract like flavoliganans and terpenoids are bound to the phospholipids like phosphatidylcholine through a polar end. Phytosomes are also called as Phytolipids delivery system. These are advanced 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 advantageously be used in treatment of acute liver diseases, either metabolic or infective origin.

Conclusion

Phytosomes are novel compounds comprising of lipophillic complexes of components of various plants like Silybum Marianum, Ginkgo Biloba, ginseng etc with phospholipids. Phytosome prepration is done by non-convectional method. Absorption of phytosome in gastro-intestinal tract is appreciably greater resulting in increased plasma level than the individual component. Complex formation ratio of component and phospholipids is 1:1 and 2:1. Phytosomes are used as a medicament and have wide scope in cosmetology. Many areas of phytosome are to be revealed in future in the prospect of pharmaceutical application. Phytosomes forms a bridge between the convectional delivery system and novel delivery system.

References

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About Authors

Dubey Darshan* ¹ , Shrivastava Satyaendra ¹ , Kapoor Shweta ¹ , Gangwal Amit ² , Dubey P.K. ³

Dubey Darshan

^1* Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 52001, India.      Tel:  +91-731-2802262, Fax: +91-731-2802467 , E-mail: darshandubey@gmail.com 

Satyaendra Shrivastava

Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 452001, India, Tel: +91-731-2802262, Fax: +91-731-2802467, E-mail: satyaendrascope@gmail.com

Shweta Kapoor

Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 452001, India

Gangwal Amit  

² Lecturer, Swami Vivekanand College of Pharmacy, Khandwa Road, Near Toll Naka, Indore (MP) 452020, India

Tel:  +91-731-3096144, E-mail: gangwal.amit@gmail.com

Dubey P.K

³ Principal, Swami Vivekanand College of Pharmacy, Khandwa Road, Near Toll Naka, Indore (MP) 452020, India

  Tel:  +91-731-3096144, E-mail:  pkdubeysvcp@rediffmail.com