STABILITY TESTING OF HERBAL NATURAL PRODUCTS AND ITS PROTOCOL.pptx

Stability testing protocol for herbal products in a detailed review.It’s the ability of formulation to retain its physical, chemical, microbiological and toxicological parameter same as that time of manufacture .

Drug product remains within specifications established to ensure its identity, strength, quality and purity.

Stability – Chemical and Physical integrity of herbal medicinal products.

Over a given time period and under the influence of environmental factors including temperature, humidity and light.
To provide evidence on how the quality of active substance varies with time and environmental factors
To establish re- test period for active substance
To establish shelf life of finished products.
To recommend storage conditions.
To evaluate the efficacy of drug.
To develop suitable packing information for drug product
To submit stability information for regulatory agencies.
1.Physical stability study:-
The original physical properties namely appearance, uniformity, palatability, dissolution, and suspend ability are maintained.

Chemical stability study:-
Each and every active ingredient retains its chemical integrity as well as potency specified on label, within the specified limits.
It involves drug assay and determination of drug degradation.

1. STABILITY TESTING OF HERBAL NATURAL PRODUCTS AND ITS PROTOCOL S.GOWTHAMRAJ M.PHARM ., Department of Pharmacognosy 1

2. CONTENTS Definition Objective Types of stability Studies Challenges in testing HMPs and steps to overcome it Types of stability Testing Stability testing Protocol Reference 2

3. DEFINITIONS It’s the ability of formulation to retain its physical, chemical, microbiological and toxicological parameter same as that time of manufacture . Drug product remains within specifications established to ensure its identity, strength, quality and purity. Stability – Chemical and Physical integrity of herbal medicinal products. Over a given time period and under the influence of environmental factors including temperature, humidity and light. 3

4. OBJECTIVE To provide evidence on how the quality of active substance varies with time and environmental factors To establish re- test period for active substance To establish shelf life of finished products. To recommend storage conditions. To evaluate the efficacy of drug. To develop suitable packing information for drug product To submit stability information for regulatory agencies. 4

5. TYPES OF STABILITY STUDY 1.Physical stability study :- The original physical properties namely appearance, uniformity, palatability, dissolution, and suspend ability are maintained. Chemical stability study :- Each and every active ingredient retains its chemical integrity as well as potency specified on label, within the specified limits. It involves drug assay and determination of drug degradation. 5

6. Microbiological stability study :- Sterility or resistance to microbial growth is maintained as per the specified requirements. Therapeutic stability study :- The therapeutic effect remains unaltered. Toxicological stability study :- No valid increase in toxicity should occurs. 6

7. MATERIAL USED FOR STABILITY STUDIES : 1.Active Pharmaceutical ingredient (API) 2.Finished pharmaceutical products Stages in stability testing :- Preformulation Final product Post marketing 7

8. CHALLENGES IN STABILITY TESTING OF HERBAL MEDICINAL PRODUCTS(HMP) : HMPs are complex in nature due to their high number of constituents. Constituents belong to different chemical classes with different analytical behaviour . Constituents sometimes have very low concentrations in the finished product. Different requirements for the different types of extracts. 8

9. STEPS TO OVERCOME CHALLENGES : 1. Use of markers for the HMPs. Marker concentration should be within ±5% When marker concentration is less in finished product then variation of ±10% Use of fingerprint chromatograms. Use of GCMS, HPTLC, HPLC and spectroscopic technique. 9

10. INTRODUCTION : Working Party on Herbal Medicinal Products (WPHMP) of the European Agency for the Evaluation of Medicinal products (EMEA) suggests guidelines on herbal stability testing. Climatic Zones for Stability Testing :- For stability testing purpose, the whole world has been divided into four zones depending upon the environmental conditions 10

11. EMEA GUIDELINE FOR HERBAL PRODUCTS INCLUDE FOLLOWING FACTS: The hygroscopic nature of extracts powder lead to flow-ability and compressibility problems. Higher moisture content can lead greater risk of cohesion and adhesion. The presence of variety of photochemical like alkaloids, glycoside, phenolic, terpenoids and steroids makes botanical chemically complex and pose challenge for analytical method development. Presence of enzyme like glycosidase , esterases or oxidases play important role in breakdown of plant secondary metabolites. 11

12. STABILITY OF THE NATURAL PRODUCTS (EMEA) Stress testing substance Accelerated stability testing Long term stability testing products 12

13. STRESS TESTING : Helps to identify the degradation products . Further help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used . Nature of Stress testing depends on the individual drug substance and the type of drug product involved . Generally conducted on a single batch of the drug substance The condition include the effect Temperatures (in 10°C increments (e.g., 50°C, 60°C,etc .) above that for accelerated testing) Humidity (e.g., 75% RH or greater) where appropriate, oxidation, and photolysis on the drug substance . The testing should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension . Perform phytochemical analysis for constitutes in given sample of HMPs by HPLC, HPTLC. 13

14. ACCELERATED STABILITY TEST: The substance or medicinal product is challenged by a controlled exaggerated stress (storage conditions) over a short time, so that the rate of degradation reaction is enhanced. In short period time, stability data can be obtained (3 – 6 months) Samples are stored at 40 C ± 2 C; 75 % ± 5 % RH for a period of 6 months . Procedure: Note down Description, identification, ph , viscosity, assay, heavy metals & microbial purity. Above parameter should match those specified in monographs or label. Transfer HMPs a ). PET Bottle with Al- cap, containing Rubber cork b ). Glass Bottle with Al- cap, containing Rubber cork. 14

15. 4.1 st set - 25°C ± 2°C / 60% RH ± 5% --------> Control condition 5.2 nd set - 40°C ± 2°C / 75% RH ± 5% -------> Accelerated condition 6.Carry out sampling at various intervals( 0 ,1, 3, 4 ,5 ,………months) 7.Perform phytochemical analysis for constitutes in given sample of HMPs by HPLC, HPTLC. 15

16. LONG TERM STABILITY TESTING: Evaluation of the physical, chemical and microbiological characteristics of a drug product over the expected duration of shelf-life under recommended storage conditions and in the proposed container/closure system . STORAGE OF STABILITY SAMPLES: STUDY Temperature Relative Humidity Time period General 25°C ± 2°C 60% RH ± 5% 12 months General 30°C ± 2°C 65% RH ± 5% 12 months Refrigerator 5°C ± 3°C ------ 12 months Freezer -20°C ± 3°C ------ 12 months 16

17. STABILITY SAMPLES TESTING FREQUENCY : Category Selection of Batches Frequency of Testing New Drug Product 1 st 3 Batch 3,6,9,12,18,24,36 months & 1 year after expiry Subsequent Batches 1 Batch every year 6,9,12,18,24,36 months & 1 year after expiry Product with primary change in packing 3 Batch 3, 6,9,12,18,24,36 months & 1 year after expiry Product with secondary change in packing 3 Batch 3, 6,9,12,18,24,36 months & 1 year after expiry 17

18. PROTOCOL FOR STABILITY TESTING Protocol is a document describing the basic components of a well controlled stability study. A well-planned stability protocol should contain the following information : Selection of batches and samples - In general, this selection should constitute a random sample from pilot or production batches that may involve a single batch or 2-3 batches Test attributes - The tests that monitor the quality, potency, purity, and identity that are expected to vary upon storage are chosen as stability tests 18

19. 3.Analytical procedures - Procedures given in the official compendia should be followed and if alternate methods are to be used, they need to be duly validated 4. Acceptance criteria - This should be fixed beforehand in the form of statistical limits for the results manifested in computable terms and pass or fail for qualitative tests 5. Storage conditions - These are based upon the marketing climatic zone of the drug. Storage condition such that thermal stability as well sensitivity to moisture can be tested. STUDY Temperature Relative Humidity Time period General 25°C ± 2°C 60% RH ± 5% 12 months General 30°C ± 2°C 65% RH ± 5% 12 months Refrigerator 5°C ± 3°C ------ 12 months Freezer Long Term -20°C ± 3°C ------ 12 months 19

20. Storage period – It generally extend from minimum of 3 or 6 months in accelerated and stress testing and up to 12, 18, or 60 months in ongoing or follow-up stability testing. Testing frequency – It should be sufficient to establish the stability profile of the drug Test schedules for different types of stability testing. 20

21. 8. Sampling plan - It involves devising for the number of samples to be placed in the stability chambers and taking out of the charged batch so as to cover the entire study . 9. Container closure system - The testing in actual containers as well as closures scheduled for marketing, are to be tested separately with proper orientation of storage of containers . 10. Evaluation - The data on quantitative attribute is analysed to determine the time duration at which 95% one-sided confidence limit for the mean curve intersects the acceptance criterion. 21

22. 11. Statements, labelling - A storage statement, retest period, and re-test date based on the stability evaluation of the drug substance should be established for the labelling. Labelling specification should match as those mentioned by regulatory authority. 22

23. THANK YOU …! “The Success of your presentation will be judged not by the knowledge you send but by what the listener receives.” - Lilly Walters. 23