Herbal Drug Formulation and Evaluation

1. Herbal Drug Formulation and Evaluation Prof. Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy, Belgaum-590010 E-mail: bknanjwade@yahoo.co.in Cell No: 0091 9742431000

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”. 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 KLE University College of Pharmacy

4. 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. KLE University College of Pharmacy

5. 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) KLE University College of Pharmacy

6. 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. KLE University College of Pharmacy

7. 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 KLE University College of Pharmacy

8. Characterization of Herbal Drug • Characterization • 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 KLE University College of Pharmacy

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

11. Oral Liquids • Uniformity of content and mass • pH • Microbial limits • Antimicrobial preservative content • Antioxidant preservative content • Extractable from container/closure system • Alcohol content KLE University College of Pharmacy

12. 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 KLE University College of Pharmacy

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

15. 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”. KLE University College of Pharmacy

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

17. Liposome Preparation KLE University College of Pharmacy

18. Liposome Preparation KLE University College of Pharmacy

19. Liposome Preparation KLE University College of Pharmacy

20. 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 Zetapotential measurements & pH sensitive probes Electrical surface potential and surface pH Minicolumn centrifugation, ion-exchange chromatography,  radiolabelling Percent of free drug/ percent capture Diffusion cell/ dialysis Drug release Physical Characterization 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 UV absorbance, Iodometric  and GLC Phopholipid peroxidation Phospholipid hydrolysis, Cholesterol auto-oxidation HPLC and TLC Osmolarity Osmometer KLE University College of Pharmacy

22. Parameter Characterization method Sterility Aerobic or anaerobic cultures Pyrogenicity Limulus Amebocyte Lysate (LAL) test Monitoring survival rates, histology and pathology Animal toxicity Biological Characterization KLE University College of Pharmacy

23. 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. KLE University College of Pharmacy

24. 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. KLE University College of Pharmacy

25. 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. KLE University College of Pharmacy

26. 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. KLE University College of Pharmacy

27. Modes of Liposome/Cell Interaction Endocytosis Adsorption Lipid transfer Fusion KLE University College of Pharmacy

28. Classes of Liposomes • Long circulating • Conventional • Immuno Cationic KLE University College of Pharmacy

29. General Case KLE University College of Pharmacy

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

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

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

35. General Case KLE University College of Pharmacy

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

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

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

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

40. Active pharmaceutical ingredients KLE University College of Pharmacy

41. Finished pharmaceutical products KLE University College of Pharmacy

42. Finished pharmaceutical products KLE University College of Pharmacy

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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 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” 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 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. KLE University College of Pharmacy

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