1. Herbal Drug Formulation and Evaluation
Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
KLE University College of Pharmacy,
Belgaum
Cell No:

2. 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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KLE University College of Pharmacy

3. 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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KLE University College of Pharmacy

4. KLE University College of Pharmacy
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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KLE University College of Pharmacy

5. KLE University College of Pharmacy
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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KLE University College of Pharmacy

6. KLE University College of Pharmacy
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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KLE University College of Pharmacy

7. KLE University College of Pharmacy
Types of Markers
Active marker:
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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KLE University College of Pharmacy

8. Characterization of Herbal Drug
Design and development consideration
Pharmacopoeial tests and acceptance criteria
Periodic/skip testing
Release versus shelf-life acceptance criteria
In-process tests
Alternative procedures
Evolving technologies
Reference standard
Statistical concepts
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KLE University College of Pharmacy

9. Herbal Drug Formulations Tablets Capsules
Oral solutions, suspensions and emulsions
Powders and granules for oral solution or suspension
Metered-dose inhalers and nasal aerosols
Nasal sprays: Solutions and suspensions
Topical, ophthalmic and Ear (otic) preparations
Suppositories
Small volume parenterals
Large volume parenterals
Transdermal patches
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KLE University College of Pharmacy

10. Hard gelatin Capsules and tablets(Coated & uncoated)
Dissolution/Disintegration
Hardness and friability
Uniformity of content and mass (dosage units)
Water content
Microbial limits
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KLE University College of Pharmacy

11. KLE University College of Pharmacy
Oral Liquids
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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KLE University College of Pharmacy

12. KLE University College of Pharmacy
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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KLE University College of Pharmacy

13. KLE University College of Pharmacy
Liposomes
Spherical vesicles with a phospholipid bilayer
Hydrophilic
Hydrophobic
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KLE University College of Pharmacy

14. 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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KLE University College of Pharmacy

15. KLE University College of Pharmacy
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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KLE University College of Pharmacy

16. Mechanical dispersion methods Solvent dispersion Detergent removal
Methods of liposomes
preparations
Passive loading
technique
Active loading
Mechanical dispersion
methods
Solvent dispersion
Detergent removal
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KLE University College of Pharmacy

17. KLE University College of Pharmacy
Liposome Preparation
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KLE University College of Pharmacy

18. KLE University College of Pharmacy
Liposome Preparation
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KLE University College of Pharmacy

19. KLE University College of Pharmacy
Liposome Preparation
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KLE University College of Pharmacy

20. 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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KLE University College of Pharmacy

21. 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, Cholesterol auto-oxidation
HPLC and TLC
Osmolarity
Osmometer
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KLE University College of Pharmacy

22. 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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KLE University College of Pharmacy

23. KLE University College of Pharmacy
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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KLE University College of Pharmacy

24. KLE University College of Pharmacy
Stability
Chemical stability :
Phospholipids, especially those derived from natural sources, are subject to two major degradative reaction :
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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KLE University College of Pharmacy

25. KLE University College of Pharmacy
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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KLE University College of Pharmacy

26. KLE University College of Pharmacy
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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KLE University College of Pharmacy

27. Modes of Liposome/Cell Interaction
Endocytosis
Adsorption
Lipid transfer
Fusion
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28. KLE University College of Pharmacy
Classes of Liposomes
Long circulating
Conventional
Immuno
Cationic
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KLE University College of Pharmacy

29. KLE University College of Pharmacy
General Case
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KLE University College of Pharmacy

30. Proposed criteria and Long-term testing conditions
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KLE University College of Pharmacy

31. Active pharmaceutical ingredient
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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KLE University College of Pharmacy

32. Active Pharmaceutical Ingredients intended for storage in refrigerator
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33. Active Pharmaceutical Ingredients intended for storage in a freezer
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KLE University College of Pharmacy

34. Finished Pharmaceutical Products
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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KLE University College of Pharmacy

35. KLE University College of Pharmacy
General Case
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KLE University College of Pharmacy

36. FPPs packaged in semi-permeable container
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KLE University College of Pharmacy

37. Example of an approach for determining water loss
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KLE University College of Pharmacy

38. FPPs intended for storage in a refrigerator
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KLE University College of Pharmacy

39. FPPs intended for storage in a freezer
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KLE University College of Pharmacy

40. Active pharmaceutical ingredients
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KLE University College of Pharmacy

41. Finished pharmaceutical products
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KLE University College of Pharmacy

42. Finished pharmaceutical products
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KLE University College of Pharmacy

43. Herbal Drug Evaluation
HPLC GC
TLC UV
LC-MS
GC-MS
HPTLC
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KLE University College of Pharmacy

44. 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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KLE University College of Pharmacy

45. 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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KLE University College of Pharmacy

46. 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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KLE University College of Pharmacy

47. 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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KLE University College of Pharmacy

48. THANKING YOU Cell No: 00919742431000 E-mail: bknanjwade@yahoo.co.in
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KLE University College of Pharmacy