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 examples of plant-derived medicine2. Explain the steps involved in standardized herbal

product production3. Describe the parameters required for standardization

and quality evaluation of herbal drug4. Define the specification of quality herbal material

LEARNING OUTCOMES

INTRODUCTIONØPlant-derived medicines is very diverse.

ØExamples:• Pure compounds• 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

Freeze/spray dried extracts

Valueadded

Source: Dr Ilham,FRIM

STANDARDIZATIONq 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 MEDICINES • The process of prescribing a set of standards (inherent characteristics),

constant parameters, definitive qualitative and quantitative values that carry an assurance of quality, efficacy, safety and reproducibility.

• STANDARDIZED EXTRACT• High quality extracts containing consistent levels of specified active

constituents and they are subjected to rigorous quality controlsduring all phases of growing, harvesting and manufacturing processes.

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

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.

Note: This is a set of standard parameter to ensure safety, quality and efficacy of herbal extract

STANDARDIZATION AND QUALITY CONTROL OF HERBALS

5. Extractive values: These are indicative weights of the extractablechemical constituents of crude drug under different solventsenvironment.

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.N

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STANDARDIZATION AND QUALITY CONTROL OF HERBALS

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 the majorclasses of constituents.

10. Toxicological studies: This helps to determine the pesticide residues,potentially toxic elements, safety studies in animals like LD50 andmicrobial assay to establish the absence or presence of potentiallyharmful microorganisms

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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:ØEvaluation 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

Problems of Herbal Products1. Reproducibility of activity.

The methods of harvesting, drying, storage, transportation, and processing (for example, mode of extraction and polarity of the extracting solvent, instability of constituents, etc.)

2. Seasonal, ecological, phenotype variation.3. Lack of standard method preparation, difficult to standardize quality criteria.

In ancient times, herbal medicine was prepared specifically on case basis (tailor made). Large scale production faces the difficulty in safety and efficacy.

Problems of Herbal Products4. Herbal drugs are usually mixtures of many constituents.5. The active principle(s) is (are), in most cases unknown.6. Selective analytical methods or reference compounds may not be

available commercially.7. Plant materials are chemically and naturally variable.8. The source and quality of the raw material are variable.

Why need standardization ?

Generally:• Consistent quality• Prevent adulteration and substitution• For safety and efficacy of consumers• Lack of regulation either national or international level• Because of great variances in plant materials

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 phytochemicalshave the advantages.

Why need standardization ?

LETS RECAP!

- Give parameters involves in standardization and quality evaluation

- State the importance of standardization of herbal product

QUALITY CONTROL

• Quality control refers to the sum of all procedures undertakento ensure the identity and purity of a particular pharmaceutical.

• Procedure from simple experiment (thin layer chromatography,infrared spectroscopy, etc.), to more complicated requirementsof pharmacopoeial monographs)

Quality definition

• Conformance to customer specification• Meeting customer expectations• Trouble-free• No problems• Zero non-conformity• No complaints from customer• No disappointments• Keeping to promises• Good service• Accurate & reliable result

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)

Summary

• The uses of plant-derived medicines is very diverse andincludes pure compound, traditionally used medicinal plants,cut or powdered botanical crude drugs, non-standardizedextracts and standardized extract.

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

• Good Practices/Techniques in Herbal Products to ensure thequality control of products.

CLASS ACTIVITY

Incoming plant

materialsProcessing Final

products

Storage & Packaging

Pre Processing Testing

Inspection• Divide into 4 groups. • Each of group will represent as a;1) Raw Material and Pre-

processing department2) Processing department3) Analysis department4) Storage & Packaging

departmentConvince the customer within the scope of factors that affect the quality of your herbs and herbal products.

CLASS ACTIVITY

FACTORS PROCEDURES

Unit 3.2 Characteristics of

Phytomedicine

PHYTOMEDICINE

• Define by Jonas: Mosby's Dictionary of Complementary andAlternative Medicine, Phytomedicine is the use of plants, parts ofplants, and isolated phytochemicals for the prevention and treatmentof various health concerns.

• also called Botanical/Plant Medicine• Chemical structures are an integral part of the study of

Phytomedicine, which indicate a plant’s pharmaceutical properties.• Pure chemical entities can be isolated and their structures elucidated.

These then can be developed into medicines

Reference: Phytomedicine. (n.d.) Jonas: Mosby's Dictionary of Complementary and Alternative Medicine. (2005). Retrieved July 28 2016 from http://medicaldictionary.thefreedictionary.com/phytomedicine

Phytomedicine Background• Phytomedicine or the use of herbal medicine with therapeutic

properties has played a significant role throughout history. Although itsusage greatly diminished during the dawn of the scientific era, there isa revival of interest in its potential by late 20th century, especially in thedevelopment of new drugs.

• Herbal medicine can be categorised into phytotherapy, over-the-counter herbal and traditional herbalism.

• There is an increase of interest in the pharmaceutical industry todevelop new medications from plants.

Factors that contribute to the increase of interest in herbal medicine:

• the inefficiency of conventional medicine (e.g. cytotoxicity, side effects andineffectiveness of synthetic drugs)

• abusive and incorrect use of synthetic drugs• the high cost involved in conventional medicine• limitations of synthetic chemistry• arises the need to find new medicines to combat the emergence of multi-

resistant pathogens• Natural products offer unmatched structural variety and their usefulness

can be extended by probing biological pathways• The cost effectiveness of modern drug development originating from

phytomedicine is now increasingly being accepted with big pharmaceuticalcompanies investing greatly

CHARACTERISTICS OF PHYTOMEDICINEPhytomedicine has some characteristics that make them unique and different from synthetic drugs;• The active principle is frequently unknown• have a wide range of therapeutic use and are suitable for chronic

treatments• Standardization, stability and quality control are feasible but not

easy –the availability and quality control are frequently problematic• Well-controlled double blind clinical and toxicological studies to prove

their efficacy and safety are rare when compared with synthetic drugs but well-controlled randomized clinical trial revealed they do exist.

• cheaper than synthetic drugs. Reference: R.N. Okigbo and E.C. Mmeka An Appraisal Of Phytomedicine In Africa KMITL Sci. Tech. J. Vol. 6 No. 2 Jul. - Dec. 2006 pg 83-94

PHYTOMEDICINE CHALLENGES

the reproducibility

of biological activity of herbal

extracts

its toxicity and adverse

effects

its adulteration and

contamination

herb–drug interactions

issues

standardisation issues

Toxicity of herbal constituents• Traditionally, herbs and herbal products have been considered to

be nontoxic and have been used by the general public andtraditional medicinal doctors worldwide to treat a range ofailments.

• Something natural does not necessarily make it safeor effective

• Active ingredients of plant extracts are chemicalsthat are similar to those in purified medications, andthey have the same potential to cause seriousadverse effects.

Toxicity of herbal constituents

• Herbs and herbal preparations can cause toxic adverse effects,serious allergic reactions, adverse drug interactions, and caninterfere with laboratory tests.

• High-risk patients such as the elderly, expectant mothers, children,those taking several medications for chronic conditions, those withhypertension, depression, high cholesterol or congestive heartfailure, should be more cautious in taking herbal medicine.

Summary• Plant-derived medicines is very diverse and includes pure compound,

traditionally used medicinal plants, cut or powdered botanical crudedrugs, non-standardized extracts and standardized extract.

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

• Good Practices/Techniques in Herbal Products ensure the quality control of products.

• Phytomedicine mixtures may be toxic and nontoxic for user.

15 MINUTES EVALUATION

1) Give the definition of standardize extract2) Give 5 parameters involves in standardization

and quality evaluation of herbal drug.3) Explain 3 factors affecting quality of herbs and

herbal product.