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

STANDARDIZATIO

N

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 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 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.

Research Laboratory Dept. of Pharmacology and theraphy

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