Herbal Drug Formulation and Evaluation

Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of Pharmaceutics
KLE University College of Pharmacy,
Belgaum-590010
E-mail: bknanjwade@yahoo.co.in
Cell No: 0091 9742431000
 Herbal Drug Formulations
Herbal formulation shall mean a dosage form
consisting of one or more herbs or processed
herb(s) in specified quantities to provide
specific nutritional, cosmetic benefits, and/or
other benefits meant for use to diagnose treat,
mitigate diseases of human beings or animals
and/or to alter the structure or physiology of
human beings or animals.

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 Herbal Medicinal Products
Any medicinal product, exclusively containing
as active substances one or more herbal
substances or one or more herbal preparations,
or one or more such herbal substances in
combination with one or more such herbal
preparations

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 Herbal Preparations
Herbal preparations are obtained by subjecting
herbal substances to treatments such as
extraction, distillation, expression,
fractionation, purification, concentration or
fermentation.

These include comminuted or powdered herbal

substances, tinctures, extracts, essential oils,
expressed juices and processed exudates.
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 Herbal Substances

All mainly whole, fragmented or cut plants, plants

parts, algae, fungi, lichen in an unprocessed, usually
dried form but sometimes fresh.

Herbal substances are precisely defined by the plant

part used and the botanical name according to the
binomial system (genus, species, variety and author)

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 Markers
Markers are chemically defined constituents or
groups of constituents of a herbal substance, a herbal
preparation or a herbal medicinal product which are
of interest for control purpose independent of whether
they have any therapeutic activity.

Markers serve to calculate the quantity of herbal

substance(s) or herbal preparation(s) in the Herbal
Medicinal Product if the markers has been
quantitatively determined in the herbal substance or
herbal preparations.
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 Types of Markers
1. Active marker:
2. Analytical marker:

Active marker are constituents or group of

constituents which are generally accepted to
contribute to the therapeutic activity.

Analytical marker are constituents or groups of

constituents that serve for analytical purpose

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 Characterization of Herbal Drug
1. Characterization
2. Design and development consideration
3. Pharmacopoeial tests and acceptance criteria
4. Periodic/skip testing
5. Release versus shelf-life acceptance criteria
6. In-process tests
7. Alternative procedures
8. Evolving technologies
9. Reference standard
10. Statistical concepts
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 Hard gelatin Capsules and
tablets(Coated & uncoated)
a) Dissolution/Disintegration
b) Hardness and friability
c) Uniformity of content and mass
(dosage units)
d) Water content
e) Microbial limits

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 Oral Liquids
a) Uniformity of content and mass
b) pH
c) Microbial limits
d) Antimicrobial preservative content
e) Antioxidant preservative content
f) Extractable from container/closure
system
g) Alcohol content
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 Oral Liquids
h) Dissolution for suspensions and powders for
suspension
i) Particle size distribution
j) Re-dispensability for suspensions
k) Viscosity for suspensions or viscous solutions
l) Specific gravity for suspensions or viscous
solutions
m) Water content for powders for reconstitution

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 Liposomes

Spherical vesicles with a phospholipid

bilayer
Hydrophilic

Hydrophobic

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 Definition of Liposome
They are simply vesicles or bags in which an aqueous
volume is entirely enclosed by a membrane composed of
lipid (fat) molecules, usually phospholipids

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 Why the Liposomes?
Liposomes have the advantage of primarily consisting
of lecithin and cholesterol, which are materials that are
occur naturally in the human body. Lecithin and
cholesterol are also present in the body in large amounts
and thus demand good bioacceptability.

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 Methods of liposomes
preparations

Passive loading Active loading

technique technique

Mechanical dispersion Detergent removal Solvent dispersion

methods methods methods

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 Liposome Preparation

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 Liposome Preparation

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 Liposome Preparation

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 Physical Characterization
Parameter Characterization method
Vesicle shape and surface Transmission electron microscopy,
morphology Freeze-fracture electron microscopy

Mean vesicle size and size Dynamic light scattering, zetasizer,

distribution Photon correlation spectroscopy, laser
light scattering, gel permeation and gel
exclusion
Surface charge Free-flow electrophoresis

Electrical surface potential and Zetapotential measurements & pH sensitive

surface pH probes

Percent of free drug/ Minicolumn centrifugation, ion-exchange

percent capture chromatography, radiolabelling

Drug release Diffusion cell/ dialysis

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 Chemical Characterization
Parameter Characterization method

Phospholipid concentration Barlett assay, stewart assay, HPLC

Cholesterol concentration Cholesterol oxidase assay and HPLC

Phopholipid peroxidation UV absorbance, Iodometric and GLC

Phospholipid hydrolysis,
HPLC and TLC
Cholesterol auto-oxidation

Osmolarity Osmometer
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 Biological Characterization

Parameter Characterization method

Sterility Aerobic or anaerobic cultures

Pyrogenicity Limulus Amebocyte Lysate (LAL) test

Animal toxicity Monitoring survival rates, histology and

pathology

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 Stability
Physical stability :
Once liposomes are formed, they behave similar to the
other colloidal particles suspended in water.

Neutral particles tend to aggregate or flocculate and

sediment with increase in size on storage. Adding
charged lipids such as stearyl amine, diactyl phosphate
and phosphatidyl serine can control the aggregation
The addition of charged lipids causes repulsion and
prevents major changes in the overall size of liposomes.

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 Stability

Chemical stability :
Phospholipids, especially those derived from natural
sources, are subject to two major degradative reaction :
A. Lipid Peroxidation :
Most phospholipid liposomes contain unsaturated acyl
chains as part of their molecular structure and
susceptible to oxidative degradation. It can be
minimized by the use of animal derived lipids like egg
PC, which has less saturated lipids, use of light
resistant containers, use of antioxidants are useful in
minimizing oxidation.
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 Stability

Chemical stability :
B. Lipid hydrolysis :
Hydrolysis in phospholipids results in the
formation of free fatty acids and lyso-lecithin.
Selecting a good source of lipid, temperature,
pH, can minimizing oxidation.

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 Stability

Biological stability :
Liposomes release entrapped molecules
rapidly when incubated with blood or plasma.
This instability is attributed to the transfer of
bilayer lipids to albumin and high density
liposomes.

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 Modes of Liposome/Cell
Interaction
Adsorption Endocytosis

Fusion Lipidtransfer

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 Classes of Liposomes
Conventional Long circulating

Immuno
Cationic

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 General Case

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 Proposed criteria and Long-term
testing conditions

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 Active pharmaceutical ingredient
1. General
2. Stress testing
3. Selection of batches
4. Container closure system
5. Specification
6. Testing frequency
7. Storage conditions
8. Stability commitment
9. Evaluation
10. Statements and labelling
11. Ongoing stability studies
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 Active Pharmaceutical Ingredients
intended for storage in refrigerator

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 Active Pharmaceutical Ingredients
intended for storage in a freezer

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 Finished Pharmaceutical Products
1. General
2. Selection of batches
3. Container closure system
4. Specification
5. Testing frequency
6. Storage conditions
7. Stability commitment
8. Evaluation
9. Statements and labelling
10. In-use stability
11. Variations
12. Ongoing stability studies
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 General Case

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 FPPs packaged in semi-permeable
container

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 Example of an approach for
determining water loss

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 FPPs intended for storage in a
refrigerator

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 FPPs intended for storage in a
freezer

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 Active pharmaceutical ingredients

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 Finished pharmaceutical products

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 Finished pharmaceutical products

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 Labelling Requirements
1. Proprietary/trade name
2. Local names
3. Dosage form of the product
4. Quantitative list of active ingredients
5. Name and address of manufacturer
6. In case of contract manufacturer
7. Distribution category
8. Precautions
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 Labelling Requirements
9. Indications and recommended dosage of the
pharmaceutical product
10. In case of products for injection
11. The batch or lot number of the product
12. The manufacturing and expiry date of the
product
13. The name and concentration (content)
14. Storage instruction and shelf-life and the
instruction keep out of the reach of children
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 Packaging Requirements
1. Name and dosage form of the product
2. Identification (description of the product and
package)
3. Quantitative list of active ingredients in a dosage
unit or suitable mass or volume or unit of the
product
4. Indications
5. Dosage regimen and directions for use
6. Contraindications

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 Packaging Requirements
7. Side effects and adverse reactions
8. Drug interactions
9. Precautions and warnings
10. Symptoms and treatment of overdose
11. Presentation (packing and packing size)
12. Storage instructions and shelf-life
13. Name and address of manufacture and country
of origin
14. Date of publication of the insert.
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 THANKING YOU
Cell No: 00919742431000
E-mail: bknanjwade@yahoo.co.in

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