STANDARISASI

OBAT HERBAL

Mae Sri Hartati Wahyuningsih

Dept. Of Pharmacology and Therapy
Faculty of Medicine
UGM

TUJUAN PEMBELAJARAN
1. Mengetahui definisi standarisasi herbal medicine.
2. Mengetahui jenis, parameter dan cara standarisasi
herbal medicine
3. Mengetahui manfaat standarisasi herbal medicine

STANDARISASI
Serangkaian parameter, prosedur dan cara pengukuran

yang hasilnya merupakan unsur-unsur terkait paradikma

mutu kefarmasian
Memenuhi syarat standar
Jaminan stabilitas produk

Proses yang menjamin bahwa produk akhir (obat,

ekstrak, produk ekstrak) mempunyai nilai parameter
tertentu yang konstan (ajeg) dan ditetapkan (dirancang
dalam formula) terlebih dahulu.

TUJUAN STANDARISASI
1.
2.
3.

Memberikan perlindungan kepada Masyarakat

melalui Safety, Quality dan Efficacy (SQE)
Menjamin konsistensi bahan penelitian.
Menjamin konsistensi produk dalam hal SQE

Herbal medicine Development Process

Phytomedicine
integrated in health
care system

Clinical
study

1.
2.
3.

Phase I
Phase II
Phase III

Formulation
development

Simple
standardization

Preclinical
study
Present
(traditional medicine)

1.
2.
3.

Toxicological study

Pharmacodynamics
study

Identity
Purity
Content or assay

Information of
safety and effects
on animal

APA YANG DISTANDARISASI

1. Proses dan metodologi

2. Produk termasuk bahan baku

3. Label termasuk klaim

Quality Control and Standardization of A

Manufactured Herbal Product
QUALITY CONTROL
HERBAL MEDICINE

RAW MATERIALS

PROCESS

SPECIFICATIONS
AND
STANDARDIZATIO
N

QUALIFICATIONS
Building (CPOTB),
Machine Tools,
environment (energy,
Water, air)
personnel

PROCESSING METHOD

TECHNOLOGY AND
FORMULATION,
CONTROL
FEED BACK PARAMETERS
(Temperature, Pressure,
Homogeneity, Stability)

VALIDASI

FINISHED PRODUCT

SPECIFICATIONS
AND
CERTIFICATION

In general, quality control is based on three

important pharmacopoeial definitions:
1. Identity

: is the herb the one it should be?

2. Purity

: are there contaminants, e.g., in the form of

other herbs which should not be there?

3. Content or assay: is the content of active constituents

within the defined limits?

Several problems not applicable to synthetic drugs

influence the quality of herbal medicine:
1. Herbal medicines are usually mixtures of many
constituents.
2. The active principle(s) is (are), in most cases unknown.
3. Selective analytical methods or reference compounds may
not be available commercially.
4. Plant materials are chemically and naturally variable.
5. The source and quality of the raw material are variable.
6. The methods of harvesting, drying, storage, transportation,

and processing (for example, mode of extraction and polarity

of the extracting solvent, instability of constituents, etc.)
have an effect.

Quality Control & Standardization of

A Plant Material

Control Quality &

Standardization of A Plant
Material

PHYTOCHEMICAL

PHYSICO - CHEMICAL
Ash Values
pH
Optical Rotation
Specific Gravity
Hardness
Disintegration Time
Elemental Composition

QC & Standardization
of A Plant Matrial

Extractive Values
Chemical Profiling
TLC Fingerprinting
Markers
- Bio-active
- Biologically
- Chemical
HPTLC/HPLC Based
Quantifications

Parameters for Standardization of Herbal Medicine

(Non Spesifik)
1. Macroscopic evaluation
2. Microscopic evaluation
3. Determination of foreign matter
4. Determination of Ash
5. Determination of heavy metals
6. Determination of microbial contaminants & aflatoxins
7. Determination of pesticide residues
8. Determination of radiative contaminations
9. Analytical methods

1. Macroscopic examination
Organoleptic evaluation of refers to the evaluation of a herbal
by colour, odour, size, shape, taste and special features
including touch, texture etc.

Macroscopic of Curcuma domestica L (kunyit)

Pieces: Mild, crumbly, brownish orange
yellow color; almost circular shape to
elliptical, sometimes branched; width of
0.5 cm to 3 cm long, 2 cm to 6 cm,
thickness 1mm to 5mm; generally curved
irregular, sometimes there is a base (upih
leaves and roots). Limit cortex and central
cylinder is sometimes unclear.
File fault: rather flat, dusty, yellow orange
to reddish-brown

1. C. longa

2.

C. xanthorrhiza

2. Microscopic examination
Today microscopic evaluation is indispensable in the initial
identification of herbs, as well as in identifying small fragments
of crude or powdered herbs, and detection of foreign matter
and adulterants.
At other times, microscopic analysis is needed to determine
the correct species and/or that the correct part of the species
is present.

Microscopic Curcuma domestica (Turmeric)

The epidermis: a single layer of cells, flat polygonal shape,
cell wall into the cork. Hair coverings: conical, straight
or slightly curved; length of 250 m to 890 m, thick
walls.
Hypodermis: consists of several layers of cells stretched
tangentially, menggabus cell wall.
Periderm: consists of 6 layers up to 9 layers of cell shaped
rectangular, cell wall into the cork.
Cortex and central silibder: parenchimatic, composed of large
cells, filled with starch.
Starch grains: single, oval or ovoid shape with one end having a
round bulge or until almost triangle with one side rounded;
lamella is less clear; less clear hilum contained in the bulge
at the end point; length of 10 m and 60 m, generally 20
m to 40 m, 10 m wide and 28 m, generally 14 m to
20 m. Cell secretion: ................ ect.

Microscopic of Berberis aristata DC.

T.S. of the root (x
100)

TLS of the root (x100)

T.S. cellular structure of stem (x 100)

Powder study (x400)

3. Determination of Foreign Matter

Herbal medicine should be made from the stated part of the

plant and be devoid of other parts of the same plant or other

plants.
They should be entirely free from harmful foreign matters

such as fungus, insects, sand, stones, poisonus, chemical

residues, microbial contaminants, ect.

For chemical residues: TLC, HPTLC, HPLC is often used to

detect the contaminants.

4. Determination of Ash
To determine ash content the plant material is burnt and the

residual ash is measured as total and acid-insoluble ash.

Total ash is the measure of the total amount of material left
after burning and includes ash derived from the part of the
plant itself and acid-insoluble ash.

5. Determination of Heavy Metals

Contamination by heavy metals such as mercury, lead,

copper, cadmium, and arsenic in herbal drugs can be

attributed to environmental pollution, and clinically relevant
dangers for the health and should therefore be limited.
The main methods commonly used are atomic absorption
spectrophotometry (AAS), inductively coupled plasma (ICP)
and neutron activation analysis (NAA).

6. Determination of microbial contaminants &

aflatoxins
Medicinal plants may be associated with a broad variety of

microbial contaminants, represented by bacteria, fungi, and

viruses.
Herbal medicine normally carry a number of bacteria and
molds, often originating in the soil. Poor methods of
harvesting, cleaning, drying, handling, and storage may also
cause additional contamination.
While a large range of bacteria and fungi are from naturally
occurring microflora, aerobic spore-forming bacteria
frequently predominate.

 The European Pharmacopoeia also specifies that E. coli

and Salmonella spp. should be absent from herbal
preparations.
However it is not always these two pathogenic bacteria that
cause clinical problems. For example, a fatal case of
listeriosis was caused by contamination of alfalfa tablets
with the Gram positive bacillus Listeria monocytogenes.

Aflatoxin-producing fungi sometimes build up during

storage. Procedures for the determination of aflatoxin
contamination in herbal drugs are published by the WHO.
After a thorough clean-up procedure, TLC is used for
confirmation.

7. Determination of pesticide residues

Herbal medicine are liable to contain pesticide residues,
which accumulate from agricultural practices, such as
spraying, treatment of soils during cultivation, and
administering of fumigants during storage.
.
Many pesticides contain chlorine in the molecule, which, for
example, can be measured by analysis of total organic
chlorine. In an analogous way, insecticides containing
phosphate can be detected by measuring total organic
phosphorus.

8. Determination of radioactive contaminations

There are many sources of ionization radiation, including

radionuclides, occurring in the environment. Hence a certain

degree of exposure is inevitable. Dangerous contamination,
however, may be the consequence of a nuclear accident.
The WHO, in close cooperation with several other
international organizations, has developed guidelines in the
event of a widespread contamination by radionuclides
resulting from major nuclear accidents.

9. Analytical methods
The quantitative determination of constituents has been

made easy by recent developments in analytical

instrumentation. Recent advances in the isolation,
purification, and structure elucidation of naturally occurring
metabolites have made it possible to establish appropriate
strategies for the determination and analysis of quality and
the process of standardization of herbal preparations.
Classification of plants and organisms by their chemical

constituents is referred to as chemotaxonomy.

 TLC, HPLC, GC, quantitative TLC (QTLC), and high-

performance TLC (HPTLC) can determine the

homogeneity of a plant extract. Over-pressured layer
chromatography (OPLC), infrared and UV-VIS spectrometry,
MS, GC, liquid chromatography (LC) used alone, or in
combinations such as GC/MS, LC/MS, and MS/MS, and
nuclear magnetic resonance (NMR), are powerful tools,
often used for standardization and to control the quality of
both the raw material and the finished product.

STANDARISASI EKSTRAK
1. Parameter Non Spesifik
a. Susut pengeringan
Tujuan:
Rentang besarnya senyawa yang hilang pada proses
pengeringan

b. Kadar air
Rentang besarnya kandungan air didalam bahan

c. Kadar abu
Gambaran kandungan mineral yang berasal
dari proses awal sampai terbentuk ekstrak.
d. Sisa pelarut
Jaminan selama proses tidak meninggalkan
sisa pelarut
e. Residu pestisida
Jaminan bahwa ekstrak tidak mengandung
pestisida melebihi nilai yang ditetapkan

f. Cemaran logam berat

Jaminan bahwa ekstrak tidak mengandung
logam berat tertentu melebihi nilai yang
ditetapkan
g. Cemaran mikroba
Jaminan bahwa ekstrak tidak mengandung
mikroba patogen dan tidak mengandung
mikroba non patogen melebihi batas yang
ditetapkan

2. Parameter Spesifik
a. Identitas ekstrak
Memberi identitas obyektif dari nama dan
spesifik dari senyawa identitas
b. Organoleptik
Pengenalan awal yang sederhana seobjektif
mungkin

c. Senyawa terlarut dalam pelarut tertentu

Memberikan gambaran awal jumlah senyawa
kandungan.

New standardization of herbal medicine

True standardization, a definite phytochemical or group of constituents

is known to have activity.

Ginkgo with its 26% ginkgo flavones and 6% terpenes is a classic

example. These products are highly concentrated and no longer

represent the whole herb, and are now considered as
phytopharmaceuticals. In many cases they are vastly more effective
than the whole herb.
Not true standardization is based on manufacturers guaranteeing the

presence of a certain percentage of marker compounds; these are not

indicators of therapeutic activity or quality of the herb.

Misal:
AKAR KUNING (Fibraurea chloroleuca Lour.)
Secara tradisional
Mengobati berak darah, sakit mata dan penurun panas badan
Sistematika tumbuhan

Divisi
Kelas
Bangsa
Suku
Marga
Jenis

: Spermatophyta
: Dicotyledonae
: Ranunculales
: Menispermaceae
: Fibraurea
: Fibraurea chloroleuca Miers.

Sinonim : Fibraurea tinctoria Lour.

Nama Indonesia: Akar kuning

Organoleptik

Warna : kuning
Bau
: tidak berbau aromatik
Rasa : pahit

SENYAWA IDENTITAS
5

15

16

14

Struktur kimia

O
8
17

13

OCH3

10

OCH3

18

12
11

8-oksoprotoberberina

Bagian batang yang digunakan

CARA PERHITUNGAN RF

RF = B = 2,3 = 0,32
A
7,2
B

3. Uji Kandungan Kimia Ekstrak

- Pola kromatogram
- Kadar total golongan senyawa
- Kadar kandungan kimia tertentu
Fase diam : Silika gel GF254
Fase gerak
{N-Heksan:Etil asetat (1:1 v/v)}
Deteksi :
a. Sinar UV254 nm
b. Sinar UV366 nm
c1. Serium(iv) sulfat
c2. Dragendorff
Pembanding:
8-oksoprotoberberina

References book
Chinese Pharmacopoeia: 1997 edition has 647 traditional

drugs.
European Pharmacopoeia: 2000 edition contains

monographs on 152 crude drugs.

Indian Pharmacopoeia: 1996 edition number shrinked to

57 including only 12 crude drugs.

Materia Medica Indonesia : 224 monographs

Indonesian Herbal Pharmacopoeia : 98 monographs of

herbs and extracts.

Research Laboratory

Dept. of Pharmacology and theraphy

Faculty of Medicine, UGM
E-mail: maeshw98@yahoo.com