T2 - Drug Stability Calculations Flashcards
Why is drug degradation considered decomposition?
A → B + C
What determines the rate of a chemical reaction?
Number of collision between reactions that is dependent on the concentration of reactants, reaction temperature, and presence of catalyst
What is the Arrhenius equation?
Used to quantify the rate of a reaction by measuring reactant and product concentrations over time
What are variables of the Arrhenius equation?
K(T) is the rate constant at temperature
A is the constant for a reaction
Ea is activation energy
R is the gas constant 8.314 J/k x mol
According to Arrhenius equation, what happens if T increases?
Higher T → larger k → increased rate of reaction
How is activation energy achieved?
An energy threshold that the reaction molecules must achieve in order to react
What determine the stability of drug products?
The maximum anticipated shelf-life that the drug product can maintain the specified strength of the drug under environmental conditions likely to be encountered in actual use
What is shelf-life?
The time interval that a drug product is expected to remain within the approve shelf-life provided it was stored under the conditions specified on the product label in the specified containers and closure-system
How do we quantify shelf-life?
The time period where 90% of the original strength in the product
What happens to a product once shelf-life is reached?
Drug is considered expired, shelf-life is used to determine expiration date of drug products
What is the importance of shelf-life studies?
Used to determine how long a drug product can reasonably by expected to maintain its quality, safety, and character
What are the test methods of conducting shelf-life studies?
Direct and indirect
What is the direct method of testing?
Storing the product under specific conditions for a longer period of time and checking it at regular intervals to see when it degrades
What are the 2 indirect methods of shelf-life study?
- Predictive models development
- Accelerated shelf-life studies
What is predictive models development?
Based on info from databases to calculate shelf-life
What is accelerated shelf-life studies?
Performed for 6 months by increasing the rate of degradation by increasing temperature (40C) and relative humidity (75%)
What happens if degradation is too significant in accelerated shelf-life studies?
Temperature and relative humidity is reduced (30C and 60%)
What is Q10?
The rate of drug/product degradation increases when the temperature is raised by 10C (rule of ten)
What is the purpose of Q10?
Allows for the prediction of a drug product’s shelf-life under real-life conditions based on results of testing at high temperatures
What is the typical Q10 value of biological conditions?
2-3 (assume 3 if value was not given)
How do we calculate Q10?
How do we calculate shelf-life?
How do we calculate shelf-life?
What are the equations associated in calculating zero-order?
What are the equations associated in calculating first-order?
