Herbal Drug Formulation and Evaluation

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Transcript Herbal Drug Formulation and Evaluation

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: [email protected]
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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Tablets
Transdermal
patches
Capsules
Oral solutions,
suspensions
and emulsions
Large volume
parenterals
Herbal Drug
Formulations
Small volume
parenterals
Suppositories
Topical,
ophthalmic
and Ear (otic)
preparations
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Nasal
sprays:
Solutions
and
suspensions
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Powders and
granules for
oral solution
or suspension
Metered-dose
inhalers and
nasal
aerosols
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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)
b)
c)
d)
e)
f)
g)
Uniformity of content and mass
pH
Microbial limits
Antimicrobial preservative content
Antioxidant preservative content
Extractable from container/closure system
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
Active loading
technique
Passive loading
technique
Mechanical dispersion
methods
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Detergent removal
methods
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Solvent dispersion
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
morphology
Transmission electron microscopy,
Freeze-fracture electron microscopy
Dynamic light scattering, zetasizer,
Photon correlation spectroscopy, laser
light scattering, gel permeation and gel
exclusion
Mean vesicle size and size
distribution
Surface charge
Free-flow electrophoresis
Electrical surface potential and
surface pH
Zetapotential measurements & pH sensitive
probes
Percent of free drug/
percent capture
Drug release
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Minicolumn centrifugation, ion-exchange
chromatography, radiolabelling
Diffusion cell/ dialysis
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Chemical Characterization
Parameter
Phospholipid concentration
Cholesterol concentration
Phopholipid peroxidation
Phospholipid hydrolysis,
Cholesterol auto-oxidation
Osmolarity
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Characterization method
Barlett assay, stewart assay, HPLC
Cholesterol oxidase assay and HPLC
UV absorbance, Iodometric and GLC
HPLC and TLC
Osmometer
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Biological Characterization
Parameter
Sterility
Pyrogenicity
Animal toxicity
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Characterization method
Aerobic or anaerobic cultures
Limulus Amebocyte Lysate (LAL) test
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
Lipid transfer
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Classes of Liposomes
Conventional
Immuno
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Long circulating
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.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
General
Stress testing
Selection of batches
Container closure system
Specification
Testing frequency
Storage conditions
Stability commitment
Evaluation
Statements and labelling
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.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
General
Selection of batches
Container closure system
Specification
Testing frequency
Storage conditions
Stability commitment
Evaluation
Statements and labelling
In-use stability
Variations
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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HPLC
GC
HPTLC
Herbal
Drug
Evaluation
TLC
GC-MS
LC-MS
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UV
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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: [email protected]
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