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Chapter-1 Introduction
Bhagwant University, Ajmer 1
1. Introduction
1.1 General
With an advent of evolution, man is dependent on plants for a variety of his needs,
namely sources of food materials, fuel, building materials, fibers, bulk chemicals,
cosmetics and also as medicines.
The medicinal plants play key role in the maintenance of world health as these are
commonly available in abundant. These plants offer mankind immediate access to safe
and effective products for use in treatment of various diseases. Medicinal plants are
valuable to modern medicine in four basic ways1.
They are used as sources of direct therapeutic agents.
They serve as raw base for elaboration of more complex semisynthetic
compounds.
The chemical structures derived from the plant sources can be used as model for
new semi-synthetic compounds.
The plants can be used as taxonomical markers for discovery of new compounds.
1.2 Herbal dosage form
Herbs have been used in a wide variety of dosage forms, since they were first discovered
to have medicinal qualities. These include the fresh or dried herb plant parts, including
the leaves, stems, roots, flower, seeds or fruits. Many herbalists promote use of the fresh
plant materials.
Herbal medicine suppliers offer plant part to be produced in form of several types of
dosage form:
Herbal products can be given as pastes obtained from mashed herbs.
Can be given as juices squeezed from herbs.
Infusion or teas, where the herb is steeped into hot water.
Decoction or extracts of herbs made by boiling the herb in water to form a
concentrate.
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Bhagwant University, Ajmer 2
Cold teas can be made where the herb is simply steeped in cold water.
Herbs pulverized into a powder and used as such or compressed into a tablet or
filled into capsules.
Herbal wines produced by fermenting the herbs with water and sugar.
Various tinctures made by extracting the herb with alcohol, glycerin or vinegar.
Liniments made with alcohol and vegetable oils used externally.
Herbal ointment (salves) made with the herb, mixed and dissolved in wax,
petroleum jelly.
Various syrups made with the herb or extract mixed into sugar, honey or glycerin
vehicles.
Poultices where the herb is moistened (cold or hot) and applied directly to a bruise
or wound and held in place with gauze.
Herbal oils usually formulated with a base oil (e.g. olive oil, sesame oil, almond
oil), the herb is placed in any of these oils allowed to stand for several days,
strained and bottled.
Several polyherbal formulations, can be obtained, which containing powder or
extracts of more than one plant drug in combination to provide a multi component
system.
Although a large number of such formulations, containing the plants with known and
proven medicinal activity, in different dosage forms are available for different
disorders. With the advances of pharmaceutical technology, more convenient dosage
forms have evolved.
At present, herbal dosage forms can be classified into two categories. The first
category contains traditional dosage forms like pills, powder, semi fluid extracts,
pellets, gelatin, tinctures, syrups, lozenges, medicated teas, wines and solutions. The
second category consists of new dosage forms developed from modern technological
processes and TCM and western medicine principles. These forms include tablets,
Chapter-1 Introduction
Bhagwant University, Ajmer 3
capsules, soluble granules, suppositories and intravenous and intra muscular
injections.
Modern herbal dosage forms offer small dosage size, and relatively good absorption
in the human body. The modern forms are more user friendly, because they are not
cumbersome to carry and can be worked into a busy schedule. Modern herbal dosage
forms have played a tremendous role in clinical treatment and have resolved problems
such as the inconvenience of preparation and administration of decoctions.
Swallowing capsule or tablets is often easier for people who cannot drink large
volumes of liquid or who do not like the bitter taste of decoctions2.
Modern herbal forms are still showing certain limitations, so the scientific and
systemic investigations are required to authenticate the medicinal value of herbal
drug.
So a scientific research plan is necessary for the improvement in the performance of
the modern herbal dosage forms, which is known to be caused due to the following
restrictions:
Poor bioavailability of herbal extracts.
Large doses of herbal extract.
Degradation of herbal extract in G.I.T.
Lack of uniformity in herbal dosage form.
Absence of localized delivery to target organ of such herbal medication.
These restrictions can be overcome by approaches to improve the therapeutic
performance of the established herbal drugs by formulating them as new drug delivery
system rather than going for cumbersome and costly research for a new entity3.
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Bhagwant University, Ajmer 4
1.3 Novel drug delivery systems
The success of Novel Drug delivery Systems (NDDS) for a number of agents has
provided unprecedented impetus for this dosage form. The traditional prosthetic role of
polymeric materials in medicinal devices is being supplemented by novel applications in
the pharmacological and pharmaceutical areas. With ever improving techniques and
methodologies and increasing pressure to find new and clinically viable dosage forms for
new and old drugs. NDDS are being developed rapidly so as to overcome the limitations
of conventional drug delivery4. Conventional drug delivery involves the formulation of
the drug into a suitable form, such as compressed tablet for oral administration or a
solution for intravenous administration. These dosage forms have been found to have
serious limitations in terms of higher doses required lower effectiveness, toxicity and
adverse effects. NDDS offer added value with a number of therapeutic benefits over
conventional dosage forms5.
Therapeutic benefits of novel drug delivery systems6
Increased efficacy of the drug.
Site specific delivery.
Decreased toxicity/side effects.
Increased convenience.
Shorter hospitalization.
Viable treatments for previously incurable diseases.
Potential for prophylactic applications.
Lower health care costs both short and long term.
Better patient compliance
Translation of the advances of various scientific disciplines in to clinical therapy will
occur only if parallel progress is made in devising new concepts to achieve delivery of
drug to the desired site of action. Fortunately, this priority has been recognized and
research on NDDS is now a major focus of attention in both academic and industrial
research laboratories. Many NDDS have been successfully developed and
commercialized and have often demonstrated better acceptance by the health system and
higher market share than the conventional delivery systems. A few NDDS available in
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Bhagwant University, Ajmer 5
the global market are; Transdermal patches, Implants, Nasal systems, Microcapsules,
Osmotic systems, Ion exchange resin systems, Pellets in capsules7.
Table 1: Novel Drug Delivery Systems8, 9, 10
System Basic Concept
Transdermal Partial rate control via polymer membrane (matrix type,
reservoir type)
Ionotophoric system External control and pulsative delivery. (Anodic and
Cathodic)
Vesicles Targeting and slow release of lipophilic and hydrophilic
drugs (liposomes and nanoparticles)
Antibody drug
conjugates
Homing potential to antigen sites (monoclonal antibody)
Osmotic pump Zero order release determined by drug/salt/osmotic agent
(for oral and rectal delivery)
Complex emulsion Slow release potential.
Implants Release over days and year possible
Responsive feedback
system
Biological control over days and year possible.
Microsphere Targeting and slow release
Phytosome Targeting and faster absorption
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Bhagwant University, Ajmer 6
1.3.1 The interest
There are number of reasons for intense interest in NDDS:
The recognition of the possibility of repatenting successful drugs by applying
concepts and techniques of controlled release drug delivery systems, coupled with
the increasing expense in bringing new drug entities to market has encouraged the
development of NDDS11
.
NDDS are needed to deliver the novel, genetically engineered pharmaceuticals
i.e. peptides and proteins to their sites of action without incurring significant
immunogenicity or biological inactivation12
.
Treating enzyme deficient diseases and cancer therapies can be improved by
better drug targeting13
.
Therapeutics and safety of drug administered by conventional route can be
improved by more precise spatial and temporal placement within the body14
.
1.3.2 The technology
Ideally the delivery system should provide therapeutics in response to physiological
requirements. It should have the capacity to sense changes and alter the drug release
process recordingly. An analytically prepared release profile is essential. Such responsive
controlled drug delivery systems, although still in its early stages, focus on two
fundamental approaches:
Externally regulated systems utilizing triggers such as magnetism, ultrasound,
temperature and electricity15
.
Self regulated systems (utilizing pH sensitive polymers, enzyme substrate
reactions). These systems release the drug to its site of action in the body in
response to patient’s therapeutic needs, rather than merely releasing quantities of
the drug at desired rates. For example, artificial pancreas system is used for
automatic administration of insulin16
.
Based on the science and technology of drug delivery, these technical
advancements can be categorized as follows:
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Bhagwant University, Ajmer 7
I. Controlled drug delivery diffusion process17
A. Polymer membrane permeation controlled:
(Drug reservoir in a rate controlling polymer matrix) 18- 20
Table 2: Marketed brands of polymer membrane permeation controlled dosage
form
NDDS Drug Therapeutic uses
Progestasert(I.U.D.) Progesterone To achieve contraception (one
year)
Occusert Pilocarpine For management of glaucoma
(One week)
Transderm Nitro Nitroglycerin For treatment of anginal attacks
(One day)
Estraderm Estradiol For treatment of post menopausal
(Three to four days)
Transderm-scop Scopolamine For prevention of motion sickness
(72 hrs.)
Catapress TTS Clonidine For treatment of hypertension (One
Week)
B. Polymer matrix diffusion controlled21, 22
Table 3: Marketed brands of Polymer matrix diffusion controlled dosage
form
NDDS Drug Therapeutic uses
Frandol tape Isosorbide dinitrate For treatment of anginal attacks
(One day)
Nitro-Dur Nitroglycerin For treatment of anginal attacks
(One day)
Compudose
Implant
Estradiol For treatment of post menopausal
syndrome. (One year)
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C. Micro reservoir dissolution controlled system20, 22
Table 4: Marketed brands of Micro reservoir dissolution controlled dosage
form
NDDS Drug Therapeutic uses
Syncro-Mate-
C-Implant
Norgestomet For control and synchronization of
estrus cycle livestock. (20 days)
Nitro-Disc Nitroglycerine For treatment of angina attacks.
(One day)
II. Controlled drug delivery by modulation process
A. Osmotically modulated
Table 5: Marketed brands of Osmotically modulated dosage form23, 24
NDDS Drug Therapeutic uses
Alzet osmotic
pump
Insulin For management of diabetes
(Several months)
Acutrim tablet Phenyl propanolamine Appetite suppression.(One
day)
Indomethacin
tablet
Indomethacin For treatment of pain
B. Hydro dynamically modulated:
Imbibation and swelling of the annular openings and thus release through the
opening e.g. for continuous delivery of insulin in treatment of diabetes25
.
C. Vapour pressure modulated:
Vapour pressure blows drug out e.g. for constant infusion of heparin in
anticoagulation treatment, for administration of insulin in antidiabetic medication,
for administration of morphine for treatment of pain in cancer26
.
D. Mechanically modulated:
Externally controlled mechanically operated systems like metered dose nebulizer
for intranasal administration of buserelin (LHRH) and insulin27
.
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E. Magnetically modulated:
Electromagnetic triggering for delivery of bovine serum albumin at controlled
rate28
.
F. Ultrasonically modulated:
Ultrasonic waves energize the drug release29
.
G. pH modulated:
pH dependent release mechanism for controlled oral aspirin30
.
H. Ion Modulated (Pennkinetic system):
Ion exchange resin and drug complex for sustained release of drugs orally31
.
I. Iontophoresis:
Drugs involved are electrochemically gradient e.g. Phoresor32
.
J. Swelling modulated:
Release is controlled by hydration induced swelling of polymeric matrix33
.
Table 6: Marketed brands of swelling modulated dosage form
NDDS Drug Therapeutic uses
Syncro-Mate-B
implants
Norgestomet For control and synchronization of
esters cycle livestock.
(Sixteen days)
Val release
tablets
Diazepam For management of anxiety and
insomnia.
K. Hydrolysis modulated:
For parenteral controlled release of naltrexone in treatment of narcotic addicts for
about three months. Drug is incorporated with biodegradable or bioerodable
polymers.34
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L. Enzymatically modulated:
Enzymatic hydrolysis of biopolymers by a specific enzyme in the target tissue.
Albumin microspheres for the controlled release of 5-fluorouracil with the aid of
protease activator in cancer treatment35
.
1.4 Carrier based delivery system
The use of carriers to target drugs to various organs is based on the fact that the
properties of the carrier determine the destination and fate of the drug entrapped in the
carrier provided that the drug leaches from the system at a suitable controlled rate.
1.4.1 Liposomes
These are artificial microscopic bilayer vesicles made of phospholipids, enclosed in
aqueous compartment. Drugs incorporated in liposomes can be delivered to the desired
site in desired concentrations without being toxic. Disease categories for liposomal drug
delivery are disease related to immune system, cancer chemotherapy, arthritis,
haemophilia, diabetes and infectious diseases. Several products undergoing clinical trials
are Doxorubicin amphotericin-B, gentamycin, vaccine for AIDS, Vincristine, and etc36.
1.4.2 Monoclonal antibodies
These are artificially produced proteins, which exhibit specificity for one single antigen.
The major application for which monoclonal antibodies are being studied for therapeutic
use is in cancer37
.
1.4.3 Nanoparticles
These are colloidal particulate systems in the sub-micron size range acting as carrier for
drug molecules. Medical applications using nanoparticles are in the treatment of
infections of reticulo-endothelial system, enzyme replacement therapy in the liver,
treatment of cancer etc38
.
1.4.4 Microspheres
These are small solid particulate carriers containing dispersed drug particles either in
solution or crystalline form. Microspheres are used as carriers for drugs and other
therapeutic agents. Some drugs under investigation for microsphere system are
Chapter-1 Introduction
Bhagwant University, Ajmer 11
mitomycin, 5-fluorouracil, progestrone, adriamycin, cisplatin, etc. Novel development is
magnetic microspheres, which have great potential in the localized tumor treatment39
.
1.4.5 Phytosome
The phytosome are newly introduced structures, which contain the active ingredients of
herb surrounded and bound by phospholipids. The phospholipid molecular structure
included a water-soluble heads and two fat soluble tails, because of their dual solubility,
phospholipid acts as an effective emulsifier. An emulsifier is a material that can combine
two liquids that normally will not mix well together. By combining the emulsifying
action of the phospholipid, with the standardized botanical extracts, the phytosome
provides dramatically enhanced bioavailability and deliver faster and improved
absorption in the intestinal tract and, because not all botanical properties are as
bioavailable as others, joining them to phospholipids produces an effective medium for
increased absorption of the active constituents of herb40
.
The flavonoids and terpenoids component of these herbal extracts lend themselves
quite well for the direct binding to phosphatidylcholine. Specially, the choline head of the
phosphatidylcholine molecules binds to these compounds, while the fat soluble
phosphatidyl portion comprising the body and tail, then enveloped the choline bound
materials. Thus, as a result a little microspheres, or cell or vesicles is produced. The term
"phyto" means plant while "some" means cell like. The phytosome process produced a
little cell, whereby valuable components of the herbal extract are protected from
destruction by digestive secretions and gut bacteria40
.
Thus the phytosome is another breakthrough technology for the development in
herbal technology. The phytosome process intensifies herbal compounds by improving
absorption, increasing bioavailability and enhancing delivery to the tissue. Some herbal
compounds are not very bioavailable, however binding them to phosphatidylcholine
produces a highly bioavailable form of the herbal compound. Several studies have shown
that the body uses phytosome molecules more effectively that non phytosome molecules.
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1.4.5.1 How does "Phytosome" differ from a "Liposome"
Liposomes are used primarily to deliver water-soluble substances.
Liposome is formed by mixing a water-soluble substance with phosphatidylcholine, no
chemical bond is formed, the phosphatidylcholine molecules collectively surround the
water soluble substance. In contrast, with the phytosome process, the phosphatidylcholine
and individual plant component actually form a 1:1 or 2:1 complex depending on the
substance. Thus in phytosome process the active constituent of herbal extract is an
integral part of the membrane, being the molecules anchored through chemical bonds to
the polar head of phospholipid. The main difference between liposome and phytosome
are shown in fig. no 1.
Fig. 1: Main difference between liposome and Phytosome40
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Bhagwant University, Ajmer 13
1.4.5.2 Advantages of phytosome
Phytosomes offer several advantages which are as follows:
Phytosome is much better absorbed than liposome because drug is in complex form
with lipid.
Entrapment efficiency is high and more ever predetermined because drug itself in
conjugation with lipid is forming vesicle.
Unlike liposome, there is no need of following the tedious, time consuming step for
removing the free, untrapped drug from the formulation.
Leakage of drug during storage does not occur in phytosome, because drug is bonded
with lipid, however loss may occur due to some chemical degradation i.e. hydrolysis.
No problem of drug incorporation.
The entrapment efficiency of drug molecule in liposome depends upon encaptured
volume and drug bilayer interaction; however it is irrelevant in phytosome.
The lipid composition in liposome decides its membrane fluidity, which in turn
influences the rate of drug release and physical stability of the system. However in
phytosome membrane fluidity depends upon the phase transition temperature of the
drug-lipid complex, but it does not affect release rate since the drug is bound. The
drug is released from phytosome by hydrolysis (including enzymatic).
The physiochemical stability of phytosome depends upon the physicochemical
properties of drug-lipid complex.
In phytosome, phospholipid transfer/exchange is reduced and solubilization by HDL
(high density lipid) is low.
Due to amphiphilic behavior, phytosome system allows, after medication, a multiple
transfer through lipophillic membrane system or tissue, through cellular walls,
piggyback endocytosis and exocytosis.
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Bhagwant University, Ajmer 14
Following absorption, their degradation velocity into active drug molecules depends
to a great extent on the size and functional groups of drug molecule, the chain length
of the lipids and the spacer. These can be varied relatively precisely for optimized in
vivo pharmacokinetics.
1.4.5.3 Method of preparation of phytosome
According to the invention, the novel complexes are prepared by reacting
equimole of natural or synthetic phospholipid, which can be phosphatidylcholine,
phosphatidylethanolamine or phosphatidylserine, with an equimole of active constituent
of herbal extract, in aprotic organic solvents such as dioxane or acetone, from which the
complex can be isolated by precipitation with non solvents such as aliphatic hydrocarbon
or by lyophilization or by freeze drying. The complex obtained after precipitation are
dried under vacuum and dissolved in organic solvent i.e. chloroform etc. and then
introduced into 250 ml round bottom flask with round glass neck. The flask is attached to
rotatory evaporator and rotated at 60 rpm. The organic solvent is evaporated under
reduced pressure, when the organic solvent is completely evaporated, the casted film is
dispersed in aqueous medium, i.e. phosphate buffer saline solution. Upon hydration the
lipid swells and peeled off from the wall of the round bottom flask and vesiculate
forming vesicles41
.
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Fig. 2: Preparation of Phytosomes
Chapter-1 Introduction
Bhagwant University, Ajmer 16
Fig. 3: Schematic Representation of Preparation of Phytosome
Active constituent
of herbal extract Phospholipid
Mixed in aprotic solvent for complex
formation with constant stirring
Complex in dry form
Complex dissolves in
organic solvent
Thin film is formed
Phytosome Suspension
Complex is isolated with
addition of nonsolvent
Drying
Hydration
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Bhagwant University, Ajmer 17
Table 7: Different Additives Employed in Formulation of Phytosomes41-47
Class Example Uses Reference
Phospholipid
Soya phosphatidyl choline
Egg phosphatidyl choline
Dipalmityl phosphatidyl
choline
Distearyl phosphatidyl
choline
Vesicles forming
component
Fuzzati et al.
Maffei et al.
Aprotic
solvent
dioxane, acetone,
methylene chloride
As a solvent Gabetta et al
Non solvent n-hexane and non solvent
i.e. aliphatic hydrocarbon
Complex
precipitating
solvent
Gabetta et al.
Alcohol
Ethanol
Methanol
As a solvent Morazzoni et al.
El-Maghraby et al.
Vanden Berge et al.
Dye
Rhodamine-123
Rhodamine-DHPE
Fluorescein-DHPE
Nile-Red
6 Carboxy fluorescence
For CSLM study Fuzzati et al.
Maffei et al.
Conti et al
Buffering
agent
Saline phosphate buffer
(pH 6.5)
7 % v/v Ethanol
Tris buffer ((pH 6.5)
As a hydrating
medium
Fuzzati et al
Conti et al.
El-Maghraby et al
Vanden Berge et al.
Chapter-1 Introduction
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Table 8: Methods for the Characterization of Phytosomes48-51
Parameter Method References
Vesicle shape
(morphology)
Transmission electron microscopy Sutarjadi et al.
Entrapment efficiency Mini column centrifugation
method
Unger
Vedavathy
Vesicle size and size
distribution
Dynamic light scattering method El-Maghraby et al.
Skin permeation
potential
Confocal laser scanning
microscopy
Fluorescence microscopy
Transmission electron microscopy
Thin layer chromatography
Simonetti et al.
Vanden Berge et al.
Surface charge and
charge density
Zeta meter Foster
Turbidity Nephlometer Sutarjadi et al.
Simonetti et al.
In vitro drug release
study
Side by side diffusion cell with
artificial or biological membrane,
Dialysis bag diffusion
Vanden Berge et al.
Gabetta et al.
Effect on the skin
structure
Histological studies
Transmission electron microscopy
Zoha et al.
Bomberdelli et al.
Stability study Dynamic light scattering method
Transmission electron microscopy
Frankel et al.
1.4.5.4 Applications of phytosome
The novel form of herbal products phytosomes are better absorbed than conventional
herbal extracts. This was observed in SILIPHOSTM
(Silybin phytosome). Silybin is
chief component of silymarin, valued for its ability to protect and restore liver.41
Phytosomes serve as a delivery system consisting of microscopic vesicles that
improve the potential bioavailability, as can be observed in skin care or nutritional
products. The phytosomes of Gingko biloba flavones, glycyrrhetinic acid, terpenes
exhibit enhanced percutaneous bioavailability40
.
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Herbal products in form of phytosomes lead to reduction in dose size. In case of
Grape seed phytosome, one 50 mg of capsule of Grape seed phytosome, in terms of
absorption only is equivalent to 50 mg of regular grape seed extract. But in terms of
biological activity, it is estimated that one 50 mg capsule of grape seed phytosome
may be as effective as 150 mg of unbound grape seed extract40
.
Phytosome as a carrier system may be employed in targeting of the herbal product at
desired site55
.
Table 9: Phytosome Preparation with their Uses
Flavonoid-Rich
Extract
Daily
dosage
Indication
Grape Seed Phytosome
50 to 100
mg
Systemic antioxidant, specific. Best
choice for most people under age of fifty.
Also specific for the eyes, lungs,
diabetes, varicose veins, and protection
against heart disease.
Green Tea Phytosome
50 to 100
mg
Systemic antioxidant. Best choice for
protection against cancer. Also protects
against damage to cholesterol.
Ginkgo Biloba
Phytosome
120 mg
Best choice for most people over the age
of 50. Protects brain and vascular lining;
SILIPHOS™
120 mg
Best choice if the liver or skin needs
additional antioxidant protection.
Milk Thistle Phytosome
150 mg
Good choice when the liver or skin only
needs minor support.
Hawthorn Phytosome
100 mg
Best choice in heart disease or high
blood pressure
Leucoselect Phytosome 50-100 mg Best choice for antioxidant support,
cardiovascular system.
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1.5 Plant profile of Emblica officinalis gaertn
Plate 1. Emblica officinalis plant in natural habitat
1.5.1Biological source
Amalaki consists of fresh fruit pulp of Emblica officinalis Gaertn. (Fam. Euphorbiaceae);
a small or medium sized tree, found in mixed deciduous forests, ascending to 1300 m on
hills and cultivated in gardens and home yards56
.
1.5.2 Geographical Source
It is planted through the deciduous of tropical India and on the hill slopes up to
2000 meter. It is commercially cultivated in the state of Uttar Pradesh in India. It is also
grown in Tamil Nadu, Rajasthan and Madhya Pradesh also.
1.5.3 Synonyms
Sanskrit: Amalaka, Amrtaphala, Dhatriphala
Assamese: Amlaku, Amlakhi, Amlakhu
Bengali: Amla, Dhatri
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English: Emblic Myrobalan
Gujrati: Ambala, Amala
Hindi: Amla, Aonla
Kannada: Nellikayi
Kashmiri: Embali, Amli
Malayalam: Nellikka
Marathi: Anvala, Avalkathi
Oriya: Anala, Ainla
Punjabi: Aula, Amla
Tamil: Nellikkai, Nelli
Telugu: Usirika
Urdu: Amla, Amlaj
1.5.4 Description
(a) Macroscopic57
Fruit, globose, 2.5-3.5 cm in diameter, fleshy, smooth with six prominant lines; greenish
when tender, changing to light yellowish or pinkish colour when mature, with a few dark
specks: taste, sour and astringent followed by delicately sweet taste.
b) Microscopic58
The epicarpic cells are rectangular in shape and their outer and radial walls are highly
cuticularized. In surface view the epicarpic cells appear polygonal in outline with thick
walls. Anomoytic type of stomata are found to be present, but rare. Collateral fibro
vascular bundles are scattered throughout the inner mesocarp. Pitted and helical tracheids
with tapering ends are seen. At places in the phloem, large cavities filled with crystal
mass are present.
1.5.5 Chemistry of Emblica officinalis 59, 60, 61
This herb has many substances, including apigenin, gallic acid, ellagic acid, chebulinic
acid, quercetin), chebulagic acid, corilagin, isostrictiniin, methyl gallate, and luteolin.
Tannins in amla include Phyllaemblicin B, emblicanin A (37%), emblicanin B (33%),
punigluconin (12%) and pedunculagin.
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Bhagwant University, Ajmer 22
O HO
O H O H
O H
Fig4: 3,4,5 Trihydroxy benzoic acid (Gallic acid)
Amla is highly nutritious and is an important dietary source of Vitamin C, minerals and
amino acids. The edible fruit tissue contains protein concentration 3-fold and ascorbic
acid concentration 160-fold compared to that of the apple. The fruit also contains
considerably higher concentration of most minerals and amino acids than apples.
Glutamic acid, proline, aspartic acid, alanine, and lysine are 29.6%, 14.6%, 8.1%, 5.4%
and 5.3% respectively of the total amino acids.
The pulpy portion of fruit, dried and freed from the nuts contains: gallic acid 1.32%,
tannin, gum 13.75%; albumin 13.08%; crude cellulose 17.08%; mineral matter 4.12%
and moisture 3.83%. Amla fruit ash contains chromium, 2.5 ppm; zinc 4 ppm; and
copper, 3 ppm.
The following products in a crystalline form from the fruit were identified as geraniin
(1), quercetin 3-b-D-glucopyranoside (2), kaempferol 3-b-Dglucopyranoside (3),
isocorilagin (4), quercetin (5) and kaempferol.
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Fig 5: Chemical structures of phenolic compounds from Emblica officinalis fruit
1.5.6 Uses
Traditionally, the fruit is useful as astringent, cardiac tonic, diuretic, laxative, livertonic,
refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic,
and digestive medicine. It is used for a variety of ailments such as anemia, hyperacidity,
diarrhea, eye inflammation, anomalies of urine, leucorrhea, jaundice, nervine debility,
liver complaints, and cough. It is reported to be effective in the treatment of peptic ulcer
and dyspepsia. It is also reported to have hepatoprotective, antioxidant, antimutagenic,
cyto protective, antitumor, antifungal, antimicrobial, hypolipidemic, and anti
atherosclerotic effects57
.
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1.5.9 Important Formulation
The plant is used in many forms. One of the most popular is as a decoction and infusion
of leaves and seeds. However, it is also used as a liquor, a fixed and an essential oil; in
confection; as a powder and also in paste and pickles. It makes an astringent extract equal
to catechu, which is prepared from the root by decoction and evapouration. The fresh
juice of the round, acidulous fruit is used in combination with that of other Myrobalans –
chebulic (Terminalia chebula) and Beleric (Terminalia belerica) in the form of a
decoction known as Triphala (three fruits). It is used as a cooling and refrigerant sherbet,
and as an astringent medicine in diarrhoea, haemoptysis (spitting blood), haematemesis
(vomiting blood) and other similar conditions58
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1.6 Plant profile of Eucalyptus globulus Labill
\
Plate 2. Eucalyptus globulus plant in natural habitat
1.6.1Biological source:
Tailapar¸ah consists of mature leaf of Eucalyptus globulus Labill. (Fam. Myrtaceae) a
large tree attaining a height of 90 m or more. .
1.6.2 Geographical Source:
Native to Australia, but planted worldwide and introduced in Nilgiris, Anamalai and
Palni hills, Simla and Shillong at an altitude of 1500-2500 m
1.6.3 Synonyms56
Sanskrit : N¢laniry¡sa, Ekalipth, Sugandha Patrah
English : Blue gum, Eucalyptus
Hindi : Yukeliptas
Malayalam : Yukkaalimaram
Marathi : Nilgiri
Tamil : Yukkaalimaram
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1.6.4: Description
a) Macroscopic
Drug consists of mature leaves, more or less scimitar shaped, thick, leathery, greyish-
green, petiolate, up to 26 cm long and 4 cm broad; petioles 2.0 to 3.5 cm long and 0.5 to
1.5 mm thick, sometimes twisted; apex acute to acuminate, base obtuse; midrib
prominent, particularly on the lower surface; margin of leaf entire and somewhat
thickened, brittle and possess numerous brown to dark brown corky warts. In transmitted
light, numerous oil glands can be seen as translucent dots; upper surface smooth, lower
surface slightly rough due to the presence of projecting veins; venation – unicostate
reticulate; lateral veins near the margin forming a continuous line; odour strong and
characteristic.
b) Microscopic
Leaf - T.S. shows typical isobilateral structures with two or three rows of palisade cells
on both upper and lower sides, surfaces show thick cuticle; numerous sunken stomata 199
and large ovoid schizogenous oil cavities of 160 to 200 μ diam.; idioblasts present with
rosettes or prismatic calcium oxalate crystals; rosette crystals 25 to 35μ in size, prismatic
crystals 15 to 25μ in size; vascular bundle of midrib are crescent shaped with one
vascular strand present on each side, all having interrupted patches of sclerenchyma;
corky warts comprising of 10 or more layers of cells; laminary bundles enclosed in
bundle sheath, the cells of which extend to the epidermis on both sides; upper and lower
epidermal cells have straight walls; stomata anomocytic; stomatal index on both upper
and lower surface 5 to 10; the palisade ratio on upper surface 5 to 17 and lower surface 3
to 6.
Powder - Yellowish brown, free flowing, characterized by the presence of cluster and
prismatic crystals of calcium oxalate; epidermis straight walled with sunken stomata;
fibers present.
1.6.5 Chemistry of Eucalyptus Globulus
Essential oil containing terpenes such as 1,8 - cineole, camphene, sabinene, myrcene, p-
menthone, α-and γ-terpinene, fenchone, α- β- thujone, citral, verbenone. Fifteen
compounds were obtained and identified as beta-sitosterol (1), betulinic acid (2),
stigmasterol (3), euscaphic acid (4), 2a-Hydroxybetulinic acid (5), macrocarpal B (6),
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macrocarpal A (7), oleanolic acid (8), 3,4,3'-O-trimethylellagic acid (9), 3-O-
methylellagic acid 4'-O-(2"-O-acetyl )-alpha-L-rhamnopyranoside (10), camaldulenside
(cypellocarpin C, 11), 3-O-methylellagic acid 4'-O-alpha-L-rhamnopyranoside (12), 3-O-
methylellagic acid (13), ellagic acid (14), and gallic acid (15).
Fig 6: Chemical Structure of rutin
1.5.6 Uses
The Eucalyptus leaf water extract presented a remarkable capacity to scavenge all the
reactive species tested, with all the 50% inhibitory concentrations being found at the
mug/mL level. Phytochemical analysis showed the presence of polyphenols such as
flavonoids (rutin and quercetin) and phenolic acids (chlorogenic acid and ellagic acid),
which may be partially responsible for the observed antioxidant activity.
The Eucalyptus plants have antibacterial and antiviral activities, use in traditional
medicine such as in the treatment of airway inflammatory diseases.