Herbal Drug Formulation and Evaluation Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department...

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

mailto:[email protected]

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”.

24/08/2011 KLE University College of Pharmacy 2

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

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.


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)


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.


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


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


Oral Liquids

a) Uniformity of content and massb) pHc) Microbial limitsd) Antimicrobial preservative contente) Antioxidant preservative contentf) Extractable from container/closure systemg) Alcohol content


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


Liposomes

– Spherical vesicles with a phospholipid bilayer

Hydrophilic

Hydrophobic


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


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”.

Methods of liposomespreparations

Passive loading technique

Active loadingtechnique

Mechanical dispersion methods

Solvent dispersion methods

Detergent removal methods


Liposome Preparation


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


Phopholipid peroxidation UV absorbance, Iodometric and GLC

Phospholipid hydrolysis, Cholesterol auto-oxidation HPLC and TLC

Osmolarity


Phospholipid concentration

Cholesterol concentration Cholesterol oxidase assay and HPLC

Osmometer

Barlett assay, stewart assay, HPLC

Chemical Characterization


Biological Characterization

Animal toxicity Monitoring survival rates, histology and pathology


Sterility

Pyrogenicity Limulus Amebocyte Lysate (LAL) test

Aerobic or anaerobic cultures


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.


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


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 :


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


Modes of Liposome/Cell Interaction

Adsorption Endocytosis

Fusion Lipid transfer


Classes of Liposomes

Conventional Long circulating

Immuno Cationic


General Case


Proposed criteria and Long-term testing conditions


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


Active Pharmaceutical Ingredients intended for storage in refrigerator


Active Pharmaceutical Ingredients intended for storage in a freezer


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

General Case


FPPs packaged in semi-permeable container


Example of an approach for determining water loss


FPPs intended for storage in a refrigerator


FPPs intended for storage in a freezer


Active pharmaceutical ingredients


Finished pharmaceutical products


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


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


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.


THANKING YOU

Cell No: 00919742431000E-mail: [email protected]


Herbal Drug Formulation and Evaluation Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department...

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