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Accelerated stability testing

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Mirza Salman Baig
Mirza Salman Baig

This document discusses accelerated stability testing and ICH guidelines. It provides definitions of stability testing and describes how exposing products to elevated temperatures can accelerate degradation reactions to predict long-term shelf life. Key points covered include common degradation reactions, advantages of accelerated testing, ICH guidance on test conditions, use of the Arrhenius equation to determine activation energy and calculate degradation rates at different temperatures, and equations for determining shelf life based on reaction order. Accelerated stability testing allows shelf life to be predicted in months rather than conducting long-term studies at room temperature.

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Accelerated stability testing & ICH (Dr.) Mirza Salman Baig Assistant Professor (Pharmaceutics) AIKTC, School of Pharmacy,New Panvel Affiliated to University of Mumbai (INDIA)
Stability • Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification.
Stability testing • A method by which a product is exposed to elevated temperature simulating what would happen over longer periods on the shelf life • Shelf life:- Time by which product remain stable and retain 90% of its initial potency. (10% degradation)
• Hydrolysis • Oxidation- reduction • Racemisation • Decarboxylation • Ring cleavage • Photolysis • isomerisation Degradation reactions
Why? • The stability of pharmaceutical preparations should be evaluated by exposing the product to normal shelf conditions for a year or extended periods. • The rate of decomposition is slow at room temperature .Such a method is time consuming and uneconomical.
Objective • To predict the shelf life of a pharmaceutical product by accelerating the rate of decomposition ,preferably by increasing the temperature. • Stability study to predict the shelf life of the product, by accelerating the rate of decomposition, preferably by increasing the temperature of reaction conditions.
Advantage • With the advancement in branch of kinetics, shelf life of a dosage form can be predicted within months based on accelerated stability reports • Preparations are subjected to high stresses during stability testing. • Common high stresses include : – Temperature – Humidity – Light
Accelerated stability testing
ICH
ICH Guidelines • These guidelines provide definitions of key terms & principles used in the stability testing of drug substances& drug products. • Q 1A (R2) :Stability testing of new drug substances & products. • Q 1B :Photo stability testing of new drug substances &products. • Q 1C :Stability testing for new dosage forms.
ICH • ICH outlined a combination of temperature & humidities for stability studies for most of the drug products. These include..... Ø -15O C ±5 C Ø 5O C ±3 C /Ambient humidity Ø 25O C±2 C /60%RH±5%, Ø 30O C±2 C/60% RH±5%, Ø 40O C±2 C/75%RH±5%.
Arrhenius equation • It explains the effect of temperature on rate of a reaction • k = A e -Ea / RT
Shelf Life • The Preparation is stored at different elevated temperatures, to accelerate the degradation • Samples are withdrawn at different time intervals • The Order of the reaction is determined by plotting the appropriate function of concentration against time and linear relationship is determined • Straight line in a graph permits the estimation of k value from the slope
Shelf Life • K value for each temperature are calculated. • By using Arrhenius relationship, Log k values are plotted against reciprocal of absolute temperature, energy of activation can be calculated. • Extrapolate the straight line to room temperature (k 25O C ) read the log k value on y-axis. • Substitute the k value in the appropriate equation to get the shelf life of the product.
Undecomposed drug available at elevated temperatures
Extrapolate graph to 25OC
Shelf life can be determined if we know k and order of reaction Order of reactio nt Equation t1/2 (Half life) 0 k0= x/t OR x=k0t t1/2= a/2k0 1 k= 2.303/t . log a/(a-x) t1/2= 0.693/k 2 k = 1/t . x/a(a-x) t1/2= 1/ak t90% t0.9= 0.9a/k t0.9=2.303/k t0.9= 1/ak

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Accelerated stability testing

  • 1. Accelerated stability testing & ICH (Dr.) Mirza Salman Baig Assistant Professor (Pharmaceutics) AIKTC, School of Pharmacy,New Panvel Affiliated to University of Mumbai (INDIA)
  • 2. Stability • Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification.
  • 3. Stability testing • A method by which a product is exposed to elevated temperature simulating what would happen over longer periods on the shelf life • Shelf life:- Time by which product remain stable and retain 90% of its initial potency. (10% degradation)
  • 4. • Hydrolysis • Oxidation- reduction • Racemisation • Decarboxylation • Ring cleavage • Photolysis • isomerisation Degradation reactions
  • 5. Why? • The stability of pharmaceutical preparations should be evaluated by exposing the product to normal shelf conditions for a year or extended periods. • The rate of decomposition is slow at room temperature .Such a method is time consuming and uneconomical.
  • 6. Objective • To predict the shelf life of a pharmaceutical product by accelerating the rate of decomposition ,preferably by increasing the temperature. • Stability study to predict the shelf life of the product, by accelerating the rate of decomposition, preferably by increasing the temperature of reaction conditions.
  • 7. Advantage • With the advancement in branch of kinetics, shelf life of a dosage form can be predicted within months based on accelerated stability reports • Preparations are subjected to high stresses during stability testing. • Common high stresses include : – Temperature – Humidity – Light
  • 9. ICH
  • 10. ICH Guidelines • These guidelines provide definitions of key terms & principles used in the stability testing of drug substances& drug products. • Q 1A (R2) :Stability testing of new drug substances & products. • Q 1B :Photo stability testing of new drug substances &products. • Q 1C :Stability testing for new dosage forms.
  • 11. ICH • ICH outlined a combination of temperature & humidities for stability studies for most of the drug products. These include..... Ø -15O C ±5 C Ø 5O C ±3 C /Ambient humidity Ø 25O C±2 C /60%RH±5%, Ø 30O C±2 C/60% RH±5%, Ø 40O C±2 C/75%RH±5%.
  • 12. Arrhenius equation • It explains the effect of temperature on rate of a reaction • k = A e -Ea / RT
  • 13. Shelf Life • The Preparation is stored at different elevated temperatures, to accelerate the degradation • Samples are withdrawn at different time intervals • The Order of the reaction is determined by plotting the appropriate function of concentration against time and linear relationship is determined • Straight line in a graph permits the estimation of k value from the slope
  • 14. Shelf Life • K value for each temperature are calculated. • By using Arrhenius relationship, Log k values are plotted against reciprocal of absolute temperature, energy of activation can be calculated. • Extrapolate the straight line to room temperature (k 25O C ) read the log k value on y-axis. • Substitute the k value in the appropriate equation to get the shelf life of the product.
  • 15. Undecomposed drug available at elevated temperatures
  • 17. Shelf life can be determined if we know k and order of reaction Order of reactio nt Equation t1/2 (Half life) 0 k0= x/t OR x=k0t t1/2= a/2k0 1 k= 2.303/t . log a/(a-x) t1/2= 0.693/k 2 k = 1/t . x/a(a-x) t1/2= 1/ak t90% t0.9= 0.9a/k t0.9=2.303/k t0.9= 1/ak