PEMBUATAN EKSTRAK

Indah Yulia Ningsih, S.Farm., M.Farm., Apt.

TOPIK KULIAH
BAHAN BAKU SEDIAAN FITOFARMASI :
SIMPLISIA
Pembuatan simplisia
Kontrol kualitas simplisia
EKSTRAK
Pembuatan ekstrak
Kontrol kualitas ekstrak

MATERI KULIAH
PEMBUATAN EKSTRAK:
Pendahuluan
Definisi ekstrak
KONTROL KUALITAS EKSTRAK

Drug development from Medicinal Plants

Traditionalmedicine
Earlysreening
Selectedmedicinalplants
Isolation

Crudedrug
Extraction
Extract
Preclinicaltest&
standardization
Standardizedextract
Clinicaltest
Phytomedicines

n
o
i
t
la
Iso

Isolate

Singlecompound
Structuremodification

Preclinicaltest

Activecompound
Clinicaltest

Phytotherapy

Pharmacotherapy

Isolasi untuk farmakoterapi

Salixalba(Willowtree)

(Kar,2007)
#

Senyawa aktif tunggal vs ekstrak

Ekstrak valeriana : valtrat,
dihidrovaltrat, asam valerenat,
valerenon efek sedatif;
Senyawa individual tidak memiliki
efek sedatif kemungkinan
sinergisme

Reasons for not isolating

Extracts known to contain a range of
similar active compounds, with well
documented clinical activity for whole or
semi-purified extract
Unsure of active constituents even if
some chemistry known
Actives known or suspected to be
unstable
Synergy or antagonism

Phytomedicines
are medicinal products that contain
plant materials as their
pharmacologically active component.
Crude drug (dried herb) or whole
extract derived from it is considered
to be the active ingredient.
Complex mixtures of compounds that
generally dont exert strong,
immediate effect.
#

Definisi Ekstrak
F.U. IX Ed. (Italian Pharmacopoeia)
Extracts are liquid (fluid extracts) or
solid (dry extracts) or of intermediate
consistency (soft extracts)
preparations obtained from
vegetable raw materials, as a rule
dried (drugs).

Definisi Ekstrak
Extracts are prepared by exhaustion
extraction with appropriate solvents, through
maceration or percolation, or other suitable
procedures, from drugs reduced to
appropriate particle size
In some cases the drugs to be extracted
must undergo preliminary treatment (for
example : inactivation of enzymes, defatting)
In other cases unwanted matter is removed
after extraction
#

Quality Control of extracts

QC of herbal materials
Medicinal plant authentication

Production methods
Total extract
Purified extract

Adjustment of Quality
Qualitative & quantitative
standardization
Extract Regulation

QC of herbal materials
Medicinal plant authentication:
Macroscopic & microscopic
Chromatographic fingerprint
Protein profiling
DNA profiling

Production Method
Two main groups of extracts :
1. Total extracts (ekstrak total)
2. Purified extracts (ekstrak
terpurifikasi)
(Bonati,1991)

Total extracts
Total or traditional extracts are extracts
that contain all the extractive matter
obtained by treating the drug with a
solvent, as a rule aqueous or hydro
alcoholic
Traditional extracts may be divided
into fluid extracts, soft extracts, and
dry extracts
(Bonati,1991)

Purified extracts
Preparations from which substances
considered useless if not actually
detrimental to the activity of the extract
have been removed
A purified extract may be obtained by
extracting the drug with a selective
solvent and/or by removing the inert
substances by various methods after the
primary extraction
(Bonati,1991)#

Purified extracts
Preparations of a purified extract must be
preceded by confirmation that the activity
of the drug is conserved; total extracts
often contain substances such as
saponins and polyphenols that are
regarded as inert but that may be crucial
to the absorption of the active principles
We have to be sure that this property has
not been lost in the purified extracts!
#

Purified extracts
Few examples of purified extract :
Extracts of Senna with a 45 to 60 %
content of sennosides
Extracts of Frangula with a 20 to 25 %
content of hydroxyanthracenes

Adjustment of Quality
Tests that essential for extracts :
Physical characteristics
Qualitative & quantitative
standardization, potential
impurities
Total aerobic microbial count

Adjustment of Quality
Physical characteristics
Traditional testing : appearance, pH,
solubility, total solids, ash
Determination of solubility of soft &
dry extracts
Particle size of dry extracts direct
compression tablet
#

Qualitative standardization
Chromatographic pattern/fingerprint
exclude adulterant
Not only for single products or family of
products, but should extend to several
substances or groups of substances
Ex : extract of boldo (Peumus boldus)
calls for the identification of boldine,
total alkaloids & flavonoids
#

Qualitative standardization
Qualitative standardization is
essential complement for
quantitative standardization of
characteristic active principles
when no specific assays are as
yet available

Qualitative standardization
The presence of several products of like
structure in an extract often
necessitates global colorimetric or
spectrophotometric determination
ex : total alkaloids, total flavonoids, etc.
(See Monografi Ekstrak Tumbuhan Indonesia
for the details)
#

Total aerobic microbial count

No Pathogen allowed
Total bacterial count: 103-104/g or /ml
can be achieved

Extract Regulation
The adjustment of phytopharmaceutical
preparation to a certain active substance
content
Extract is regarded as the active component
of a medicine designated as a
pharmaceutical formulation, not an individual
substance contained in it
Original ratio of active substances is
preserved within acceptable limits
(List&Schmidt,
#
1989)

Drugwithstandard
content

Drugwithlower
content

Drugwithtoohigh
content

Mixed&adjusted

Liquidextracttoo
weak

Liquidextracttoo
strong

Liquidmixture
adjusted
Extracttoo
weak

Extracttoo
strong
(List&Schmidt,1989)

Regulated
Extracts

Adding the inert adjuvant

1. The miscella is evaporated down to a

thin extract under the careful condition

given in the particular Pharmacopoeia
& this extract broth is then weighed.
The dry residue & the active
substance content of aliquot portions
of it are determined. The thin extract is
then adjusted to the required quantity
of dextrin or lactose
#

Adding the inert adjuvant

(100 R) a
x = ---------------- - T
b
a=
b=
R=
T=
x=

weight of active substance (g) in the extract broth

required content of active substances in dry extract
(%)
permitted residual moisture in dry extract (%)
weight of the dry residue of the total extract broth
(g)
weight of adjuvant substances to be added (g)
#

Adding the inert adjuvant

2. The miscella is evaporated to dryness;

if only small quantity of it are available

it is ground with the required quantity
of adjuvant substance. When large
technical quantities are being
processed, the dry extract, ground as
fine as possible, must be mixed
homogenously with the calculated
quantity of adjuvant substance in
suitable mixers
#

TEKNOLOGI
EKSTRAKSI
TUMBUHAN OBAT

Penyiapan bahan baku

sediaan Fitofarmasi
Budidaya tumbuhan obat
Teknologi paska panen
Teknologi ekstraksi

Extraction
Extraction, as the term is used
pharmaceutically, involves the
separation of medicinally active portions
of plant or animal tissues from the
inactive or inert components by using
selective solvents in standard extraction
procedures
#

The principle of solid-liquid extraction

When a solid material comes in contact with a
solvent, the soluble components in the solid
material move to the solvent.
Thus, solvent extraction of plant material results in
the mass transfer of soluble active principle
(medicinal ingredient) to the solvent, and this takes
place in a concentration gradient.
The rate of mass transfer decreases as the
concentration of active principle in the solvent
increases, until equilibrium is reached, i.e. the
concentrations of active principle in the solid
material and the solvent are the same.
#

The principle of solid-liquid extraction

Thereafter, there will no longer be a mass
transfer of the active principle from plant
material to the solvent.
Since mass transfer of the active principle
also depends on its solubility in the solvent,
heating the solvent can enhances the mass
transfer.
Moreover, if the solvent in equilibrium with
the plant material is replaced with fresh
solvent, the concentration gradient is
changed. This gives rise to different types of
extractions: cold percolation, hot percolation
and maceration
#

Plant Products

Impureliquids
Semisolids
Powders

Decoctions
Infusions
Fluidextracts
Tinctures
Pilular(semisolid)extracts
Powderedextracts

Standardized extraction procedures

to attain the therapeutically desired
portion and to eliminate the inert
material by treatment with a selective
solvent known as menstruum

Standardized extraction procedures

MedicinalHerbs

Extracts
Fractions

Tinctures
Fluidextracts

Isolate

Drug

General Methods of Extraction

Maceration
Infusion
Decoction
Digestion
Percolation
Hot Continuous Extraction (Soxhlet)
Aqueous Alcoholic Extraction by
Fermentation
#

General Methods of Extraction

Counter-current Extraction
Ultrasound Extraction (Sonication)
Supercritical Fluid Extraction
Phytonics Process

Aqueous Alcoholic Extraction by

Fermentation
Soaking the crude drug, in the form of either
a powder or a decoction (kasaya), for a
specified period of time, during which it
undergoes fermentation and generates
alcohol in situ; this facilitates the extraction of
the active constituents contained in the plant
material.
The alcohol thus generated also serves as a
preservative
Ayurvedic preparation : karpurasava,
kanakasava, dasmularista
#

Counter-current Extraction (CCE)

Wet raw material is pulverized using toothed disc
disintegrators to produce a fine slurry
The material to be extracted is moved in one
direction (generally in the form of a fine slurry) within
a cylindrical extractor where it comes in contact with
extraction solvent.
The further the starting material moves, the more
concentrated the extract becomes.
Complete extraction is thus possible when the
quantities of solvent and material and their flow rates
are optimized.

Counter-current Extraction (CCE)

Advantages :
i. A unit quantity of the plant material can be
extracted with much smaller volume of solvent as
compared to other methods like maceration,
decoction, percolation.
ii. CCE is commonly done at room temperature,
which spares the thermolabile constituents from
exposure to heat which is employed in most other
techniques.
iii. As the pulverization of the drug is done under wet
conditions, the heat generated during comminution
is neutralized by water.
iv. The extraction procedure has been rated to be
more efficient and effective than continuous hot
extraction.
#

Ultrasound Extraction (Sonication)

The use of ultrasound with frequencies
ranging from 20-2000 kHz; this increases the
permeability of cell walls and produces
cavitation.
One disadvantage of the procedure is the occasional
but known deleterious effect of ultrasound energy
(more than 20 kHz) on the active constituents of
medicinal plants through formation of free radicals
and consequently undesirable changes in the drug
molecules.
#

Supercritical Fluid Extraction

Extraction using CO2 at critical point
Organic solvents are frequently added
to CO2 extracting fluid to alleviate the
polarity limitations
Generally, cylindrical extraction vessels
are used for SFE
#

Supercritical Fluid Extraction

Advantages :
i. The extraction of constituents at low
temperature, which strictly avoids
damage from heat and some organic
solvents.
ii. No solvent residues.
iii. Environmentally friendly extraction
procedure.
#

Phytonics Process
Developed & patented by Advanced Phytonics
Ltd (Manchester, UK)
The solvent is 1,1,2,2-tetrafluoroethane, better
known as hydrofluorocarbon-134a (HFC-134a)
as a replacement for chlorofluorocarbons
(CFC).
The b.p. of this solvent is -25 C. It is not
flammable or toxic.
Unlike CFC, it does not deplete the ozone
layer.
It has a vapor pressure of 5.6 bar at ambient
temperature.
#

Phytonics Process
Advantages :
Unlike other processes that employ high
temperatures, the phytonics process is cool and
gentle and its products are never damaged by
exposure to temperatures in excess of ambient.
No vacuum stripping is needed which, in other
processes, leads to the loss of precious volatiles.
The process is carried out entirely at neutral pH
and, in the absence of oxygen, the products never
suffer acid hydrolysis damage or oxidation.
The technique is highly selective, offering a choice
of operating conditions and hence a choice of end
products.
#

Phytonics Process
Advantages :
It is less threatening to the environment.
It requires a minimum amount of electrical energy.
It releases no harmful emissions into the
atmosphere and the resultant waste products
(spent biomass) are innocuous and pose no
effluent disposal problems.
The solvents used in the technique are not
flammable, toxic or ozone depleting.
The solvents are completely recycled within the
system.
#

Selecting an Appropriate Extraction

Method
Authentication of plant material should be
done before performing extraction. Any
foreign matter should be completely
eliminated.
Use the right plant part and, for quality control
purposes, record the age of plant and the
time, season and place of collection.

Selecting an Appropriate Extraction

Method
Conditions used for drying the plant material
largely depend on the nature of its chemical
constituents.
Hot or cold blowing air flow for drying is
generally preferred.
If a crude drug with high moisture content is
to be used for extraction, suitable weight
corrections should be incorporated.

Nature of constituents
If the therapeutic value lies in non-polar
constituents, a non-polar solvent may be
used
ex : lupeol (Crataeva nurvala) hexane
If the therapeutic value lies in polar
constituents, a polar solvent may be used
ex : glycosides (Bacopa monnieri & Centella
asiatica) aqueous methanol

Nature of constituents
If the constituents are thermolabile,
extraction methods like cold maceration,
percolation and CCE are preferred.
For thermostable constituents, Soxhlet
extraction (if nonaqueous solvents are used)
and decoction (if water is the menstruum)
are useful.

Nature of constituents
Constituents that degrade while being kept in
organic solvents : flavonoids and phenyl
propanoids
Higher than required temperature should be
avoided. Some glycosides are likely to break
upon continuous exposure to higher
temperature

Standardization of time of extraction

Insufficient time means incomplete extraction.
If the extraction time is longer, unwanted
constituents may also be extracted.
If tea is boiled for too long, tannins are
extracted which impart astringency to the
final preparation.

Extraction steps
1.
2.
3.
4.
5.

Size reduction
Extraction
Filtration
Concentration
Drying

TERIMA KASIH