Herbal Drug Formulation and Evaluation
Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of PharmaceuticsKLE University College of Pharmacy,
Belgaum-590010E-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
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• 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
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 concepts24/08/2011 KLE University College of Pharmacy 8
Hard gelatin Capsules and tablets(Coated & uncoated)
a) Dissolution/Disintegrationb) Hardness and friabilityc) Uniformity of content and mass (dosage
units)d) Water contente) Microbial limits
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Oral Liquids
a) Uniformity of content and massb) pHc) Microbial limitsd) Antimicrobial preservative contente) Antioxidant preservative contentf) Extractable from container/closure systemg) Alcohol content
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Oral Liquids
h) Dissolution for suspensions and powders for suspension
i) Particle size distributionj) Re-dispensability for suspensionsk) Viscosity for suspensions or viscous solutionsl) Specific gravity for suspensions or viscous
solutionsm) 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?
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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”.
Methods of liposomespreparations
Passive loading technique
Active loadingtechnique
Mechanical dispersion methods
Solvent dispersion methods
Detergent removal methods
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Physical Characterization
Surface charge Free-flow electrophoresis
Electrical surface potential and surface pH
Zetapotential measurements & pH sensitive probes
Percent of free drug/ percent capture
Drug release Diffusion cell/ dialysis
Parameter Characterization method
Vesicle shape and surface morphology
Mean vesicle size and size distribution
Dynamic light scattering, zetasizer, Photon correlation spectroscopy, laser light scattering, gel permeation and gel exclusion
Minicolumn centrifugation, ion-exchange chromatography, radiolabelling
Transmission electron microscopy, Freeze-fracture electron microscopy
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Phopholipid peroxidation UV absorbance, Iodometric and GLC
Phospholipid hydrolysis, Cholesterol auto-oxidation HPLC and TLC
Osmolarity
Parameter Characterization method
Phospholipid concentration
Cholesterol concentration Cholesterol oxidase assay and HPLC
Osmometer
Barlett assay, stewart assay, HPLC
Chemical Characterization
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Biological Characterization
Animal toxicity Monitoring survival rates, histology and pathology
Parameter Characterization method
Sterility
Pyrogenicity Limulus Amebocyte Lysate (LAL) test
Aerobic or anaerobic cultures
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StabilityPhysical 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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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.
Stability
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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.
Stability
Chemical stability :
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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.
Stability
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Modes of Liposome/Cell Interaction
Adsorption Endocytosis
Fusion Lipid transfer
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Classes of Liposomes
Conventional Long circulating
Immuno Cationic
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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 Products1. 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 studies24/08/2011 KLE University College of Pharmacy 34
Labelling Requirements
1. Proprietary/trade name2. Local names3. Dosage form of the product4. Quantitative list of active ingredients5. Name and address of manufacturer6. In case of contract manufacturer7. Distribution category8. Precautions
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Labelling Requirements9. 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”24/08/2011 KLE University College of Pharmacy 45
Packaging Requirements
1. Name and dosage form of the product2. 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 product4. Indications5. Dosage regimen and directions for use6. Contraindications
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Packaging Requirements
7. Side effects and adverse reactions8. Drug interactions9. Precautions and warnings10. Symptoms and treatment of overdose11. Presentation (packing and packing size)12. Storage instructions and shelf-life13. Name and address of manufacture and country
of origin14. Date of publication of the insert.
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THANKING YOU
Cell No: 00919742431000E-mail: [email protected]
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