UNIT 3: PLANT EXTRACT-DERIVED PHARMACEUTICALS

AND NUTRACEUTICALS

3.1 Production, standardization and Quality control

3.2 Characteristics of phytomedicine

At the end of the unit 3, students should be able to:1. List the uses of plant derived medicine2. Explain the steps involve in standardize herbal

product production3. Describe the parameter required for

standardization and quality evaluation of herbal drug

4. Define the specification of quality herbal material

LEARNING OUTCOMES

INTRODUCTIONThe used of plant-derived medicines is very diverseand includes:• Traditionally used medicinal plants• Cut or powdered botanical crude drugs• Non-standardized extracts• Standardized extracts

Nutraceutical products

Pharmaceutical products

MARKET VALUE OF HERBAL PREPARATIONS

Fresh materials (roots, leaves, etc)

Dried powder

Non-standardized extract

Standardized extract

Phytomedicine

Freeze/spray dried extracts

Valueadded

Source: Dr Ilham,FRIM

General protocol for standardized herbal product/extract production

Raw materials

Source identification

Storage condition

manufacturingProcessed materials

Packaging & storage Finished products

analysis analysisanalysis

analysis

Stability test

Singh & Bagchi 2002 in Medicinal plants

Standardization & standardized extract• Standardization

- Standardization of herbal medicines is the process ofprescribing a set of standards (inherentcharacteristics), constant parameters, definitivequalitative and quantitative values that carry anassurance of quality, efficacy, safety and reproducibility.

• Standardized extract• High quality extracts containing consistent levels of

specified, and they are subjected to rigorous qualitycontrols during all phases of growing, harvesting, andmanufacturing processes.

STANDARDIZATIONq It is the process of developing and agreeing upon technical

standardsqSpecific standards are worked out by experimentation and

observations, which would lead to the process of prescribing a set ofcharacteristics exhibited by the particular herbal medicine.

STANDARDIZATION IS A TOOL IN THE QUALITY CONTROL PROCESS

Standardization of Herbal drugs (Raw Drugs)

ØCorrect taxonomic identification & authenticationØStudy on the medicinal part: root, stem, bark, leaves, flowers, fruits,nuts,

gum, resins etc.ØCollection details: Location, stage & development/ growth of the plants,

time, pre-processing storage etc.ØOrganoleptic examination of raw drug:

Evaluation by means of sensory organs: touch, odour taste

ØMicroscopic & molecular examinationØChemical composition (TLC, GLC, HPLC, DNA fingerprinting)ØBiological activity of the whole plantØShelf life of raw drugs

Standardization of Herbal drugs (Herbal Formulation)ØFollow defined Good Manufacturing Practices (GMP)ØScientific Verification

Toxicity evaluationChemical profilingPharmacodynamics – effect of drug in the bodyPharmacokinetics – absorption, distribution, metabolism, mechanism of action and executionDosageStability and shelf lifePresentation and PackingTherapeutic merits – Compared with other drugs

QUALITY EVALUATION OF HERBAL DRUGS

Standardization & Quality Evaluation of Herbal drugs

Physico-chemical value

Parameters required for quality evaluation of

herbal drugs

STANDARDIZATION AND QUALITY CONTROL OF HERBALS

1. Macro and microscopic examination: For Identification of right varietyand search of adulterants.2. Foreign organic matter: This involves removal of matter other thansource plant to get the drug in pure form.3. Ash values: These are criteria to judge the identity and purity of crudedrug – Total ash, sulphated ash, water soluble ash and acid insoluble ashetc.4. Moisture content: Checking moisture content helps reduce errors in theestimation of the actual weight of drug material. Low moisture suggestsbetter stability against degradation of product.5. Extractive values: These are indicative weights of the extractablechemical constituents of crude drug under different solvents environment.N

ote:

Thi

s is a

set o

f sta

ndar

d pa

ram

eter

to e

nsur

e sa

fety

, qua

lity

and

effic

acy

of h

erba

l ext

ract

6. Crude fibre: This helps to determine the woody material component,and it is a criterion for judging purity.7. Qualitative chemical evaluation: This covers identification andcharacterization of crude drug with respect to phytochemicalconstituent. It employs different analytical technique to detect andisolate the active constituents. Phytochemical screening techniquesinvolve botanical identification, extraction with suitable solvents,purification, and characterization of the active constituents ofpharmaceutical importance.8. Chromatographic examination: Include identification of crude drugbased on the use of major chemical constituents as markers.9. Quantitative chemical evaluation: To estimate the amount of themajor classes of constituents.10. Toxicological studies: This helps to determine the pesticideresidues, potentially toxic elements, safety studies in animals like LD50and Microbial assay to establish the absence or presence of potentiallyharmful microorganisms

Problems of Herbal Products1. Reproducibility of activity.2. Seasonal, ecological, phenotype variation.3. Lack of standard method preparation, difficult to standardize quality criteria.4. In ancient times, herbal medicine was prepared specifically on case basis (tailor

made), now large scale production faces the difficulty in safety and efficacy.5. Herbal drugs are usually mixtures of many constituents.6. The active principle(s) is (are), in most cases unknown.7. Selective analytical methods or reference compounds may not be available

commercially.8. Plant materials are chemically and naturally variable.9. The source and quality of the raw material are variable. 11. The methods of harvesting, drying, storage, transportation, and processing (for example, mode of extraction and polarity of the extracting solvent, instabilityofconstituents, etc.)

Why need standardization ?Generally:• Reproducible and higher quality of product (consistent quality)• Allow comparison of the clinical effectiveness, pharmacological

effect and side effects.• Give patients greater security; increase the level of trust in

herbal product. • For safety and efficacy of consumers• Prevent adulteration and substitution• Lack of regulation either national or international level• Because of great variances in plant materials

Why need standardization ?

Specifically (high demand)• Estimate 80% of the world population is still

depending on herbal products for primary healthcare needs.

• Growing rate is 7% per year expected to reach US$ 5 trillion by 2050.

• There is a global increase for plant based products.

Why need standardization ?

Specifically (the effects)• Side effects of modern drug.• Higher concentration of modern drugs compared to herbal

medicine.• Herbal medicine is not suitable for emergency cases, but for

chronic diseases such as cancer, high blood pressure, allergies, welllness, diabetes-multifactorial, hence complex mixture of phytochemicals have the advantages.

Lets do…2 MINUTES PAPER

- Give 5 parameter involves in standardization and quality evaluation

- State importance of standardization of herbal product

QUALITY CONTROLQuality control refers to the sum of all procedures undertaken toensure the identity and purity of a particular pharmaceutical.- Procedure from simple experiment (thin layer chromatography, infraredspectroscopy, etc.), to more complicated requirements of pharmacopoeialmonographs)

Quality definition

QUALITY SPECIFICATION OF HERBAL MATERIALS

Based on 3 important pharmacopeial definitions:1. Sample identity authentication

• Botanical name, local name, family name, harvesting time, method of collection, handling, habitat, physical appearance, sensory character, photograph

2. Purity (foreign matter, mineral content, ash values) to reduce contaminant.

3. Assay (biological activity, clinical trials) to ensure the active constituents within the defined limit.

REQUIREMENT FOR QUALITY CONTROL IN HERBAL PRODUCTION

• Adequate facilities for production & analysis.• Trained personnel for manufacturing & analysis• Approved procedures for process & analysis.• Validated test methods for analysis.

Good Practices/Techniques in Herbal Products

Good storage practice (GSP)

Good manufacturing practice (GMP)

Good laboratory practice (GLP)

FINAL PRODUCT!

Good agricultural practice (GAP)

Good harvesting practice (GHP)

Factors affecting quality of herbs and herbal products

Class activityMadam Liyana is a director of herbal product company. She intended to buy the product from your company if the quality of the product meets her requirement.• Divide into group. Each of group will represent as a;1) Raw material supplier – technique in planting, harvesting, fertilizer use2) Pre processing department – washing, grading, drying3) Processing department – extraction, mixing using the appropriate method4) Testing department- stability test5) Storage & Packaging- location condition for storage, material use in packaging, design• Explain it within the scope of the factor and convince your

customer the quality of your product

For guidance

Incoming plant

materialsProcessing Final

products

Storage & Packaging

Pre Processing Testing

Inspection

Summary

• The used of plant-derived medicines is very diverse andincludes traditionally used medicinal plants, cut or powderedbotanical crude drugs, non-standardized extracts andstandardized extract.

• There are several parameters required for standardizationand quality evaluation of herbal drugs

• Good Practices/Techniques in Herbal Products are to ensurethe quality control of products.