Kinetics 2 Flashcards
Kinetics- temperature
- Stability testing of a drug within a formulation is not feasible for the duration of its shelf-life is measured using traditional methods
- Measure k (1-5 years)
- How do we test for stability but without having to measure how quickly a drug degrades, when this may take many years
- Accelerated stability testing (Arrhenius Equation)
- The impact of temperature on stability
Temperature and stability-Arrhenius Theory
Temperature
-Chemical reaction occurs at finite rates
-Collisions between molecules are veru frequent
E.g. some reactions occur rapidly
Arrhenius (1897)
-Normal molecules do not undergo reaction
-Only those: with an energy above a certain critical level
+Energy of activation (Ea)- energy barrier before reaction occurs
-Critical energy for reaction
Arrhenious equation (2)
-Arrhenius developed an equation which now widely used to relate a reaction rate constant to an activation energy and temperature
-This has now been adopted within the pharmaceutical industry in what are called
+Accelerated stability testing
+Used to ESTIMATE drug stability at different temperatures. CArry out experiment once at certain temperature, obtain equations, use equation to assess drug stability at other temperatures
Temperature and stability
kt= Ae(-Ea/RT) =ln(kt)= ln(A) - Ea/R x 1/T kt= rate constant at temp t A= Constant value (frequency or pre-exponentail facor; same units of kt) Ea= activation energy T= temperature in kelvin (273+'C) R=Gas constant (8.314)
Temperature Arrhenius equation
-Plot 1/T in kelvin against each reaction rate constant and each temperature
ln(kt)= y
ln(A)= c
-(E/R)= m
-1/T= x
-Linear relationship between k and T can measure (experimentally) or estimate k for different temperatures
-Ea (Activation energy)= slope*R
Arrhenious equation- Ea and A examples
Degradation of penicillin T: 30 : 40: 50 : 60: kT:1.554: 4.860:14.16:38.71 1) Convert into kelvin 2) then 1/T 3) Natural log kT
