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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. Memberikan perlindungan kepada
Masyarakat melalui Safety, Quality dan
Efficacy (SQE)
2. Menjamin konsistensi bahan penelitian.
3. Menjamin konsistensi produk dalam hal
SQE
Herbal medicine Development Process
Simple standardization
Clinical study
Formulation development
Toxicological study
Pharmacodynamics study
Information of safety and effects on animal
1. Identity 2. Purity 3. Content or assay
1. Phase I 2. Phase II 3. Phase III
Phytomedicine integrated in health care system
Present (traditional medicine)
Preclinical study
APA YANG DISTANDARISASI
1. Proses dan metodologi
2. Produk termasuk bahan baku
3. Label termasuk klaim
QUALITY CONTROL
HERBAL MEDICINE
RAW MATERIALS PROCESS PROCESSING METHOD FINISHED PRODUCT
VALIDASI
SPECIFICATIONS
AND
STANDARDIZATION
SPECIFICATIONS
AND
CERTIFICATION
TECHNOLOGY AND
FORMULATION,
CONTROL
FEED BACK PARAMETERS
(Temperature, Pressure,
Homogeneity, Stability)
QUALIFICATIONS Building (CPOTB),
Machine Tools,
environment (energy,
Water, air)
personnel
Quality Control and Standardization of A
Manufactured Herbal Product
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?
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.
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.
Control Quality &
Standardization of A Plant
Material
Quality Control & Standardization of
A Plant Material
QC & Standardization
of A Plant Matrial
PHYSICO - CHEMICAL • Ash Values
• pH
• Optical Rotation
• Specific Gravity
• Hardness
• Disintegration Time
• Elemental Composition
PHYTOCHEMICAL • 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.
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
Macroscopic of Curcuma domestica L (kunyit)
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.
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 µm to 890 µm, 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 µm and 60 µm, generally 20
µm to 40 µm, 10 µm wide and 28 µm, generally 14 µm to
20 µm. Cell secretion: ................ ect.
Microscopic Curcuma domestica (Turmeric)
Microscopic of Berberis aristata DC.
T.S. of the root (x
100) T.S. cellular structure of stem (x
100)
TLS of the root
(x100) Powder study (x400)
• 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.
3. Determination of Foreign Matter
• For chemical residues: TLC, HPTLC, HPLC is often used to
detect the contaminants.
• 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.
4. Determination of Ash
• 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.
5. Determination of Heavy Metals
• 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
• 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.
• 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.
.
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
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.
2. Parameter Spesifik
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 : Spermatophyta
Kelas : Dicotyledonae
Bangsa : Ranunculales
Suku : Menispermaceae
Marga : Fibraurea
Jenis : Fibraurea chloroleuca Miers.
Sinonim : Fibraurea tinctoria Lour.
Nama Indonesia: Akar kuning
Organoleptik
• Warna : kuning
• Bau : tidak berbau aromatik
• Rasa : pahit
Bagian batang yang digunakan
N
O
O1
3
4 5
6
8
9
10
11
12
13
14
15
16
17
18
O2
OCH3
OCH3
8-oksoprotoberberina
Struktur kimia
SENYAWA IDENTITAS
CARA PERHITUNGAN RF
RF = B = 2,3 = 0,32
A 7,2
A
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.
THANK YOU