Drug Stability 1 Flashcards
How is reaction rate measured/monitored?
By monitoring the decrease in concentration of reactants over time
What does the order of the reaction mean? Give an example of what it looks like
Order of the reaction is the number of concentration terms required to determine the rate
Rate = [A]m[B]n = k[A]m[B]n
M + N = sum of the exponents = order of the reaction
In pharmacy first, second and zero order reactions are of most interest
What is rate proportional to the product of? Give an example of what this looks like
Rate is proportional to product of the molar concentrations of each reactant raised to the power of its stoichiometric coefficient
Rate is proportional to [A][B] = k [A]<span>X</span>[B]<span>Y</span>
EXAMPLE: mA + nB –> xC + yD
Rate is proportional to [A]m[B]n = k[A]m[B]n
K = rate constant
What does the rate constant (K) mean? What are the factors that increase/decrease K?
> use Arrhenius equation to see the relationship between rate constant and temperature/activation energy
A constant that indicates the relationship between the molar concentration of reactants and the rate of a chemical reaction
Increased temperature = increased rate constant = increased rate
Increased activation energy = decreased rate constant = decreased rate
Rate = k[A]m[B]n
For a first-order reaction (kinetics);
A) What conditions are required for it to occur?
B) What is the formula for the rate of reaction?
C) What happens to the concentration over time?
D) What type of drug form does it occur in?
E) Draw a labeled plot of what log concentration against time looks like
F) Gradient?
G) Units of K (rate constant)?
A)
- Occurs when the rate of reaction is determined by molar concentration of ONE reactant (occurs when there is only one reactant)
- OR when the concentrations of other reactants are held constant
B)
- Rate of reaction = k * [molar conc. of reactant] OR - (dC/dt)
C)
- concentration decreases exponentially with time
D)
- Normally applies to drugs formulated under certain conditions in SOLUTION
E)
See attached image
F)
-k/2.303
G)
s-1 (time-1)
For a first-order reaction (kinetics);
A) What is the formula for half-life? Is it constant in first-order reactions?
B) Is rate constant (K) and half-life dependent or independent of initial concentration of reactants?
C) Is rate dependent or independent on concentration of reactants?
Half life is the time for concentration to fall to half its value
A)
t1/2 = 0.693/k1
It is constant for first order reactions
B)
Rate CONSTANT and half-life are independent of the initial concentration of reactants
C)
Rate is dependent on concentration and proportional to the amount present at any time.
> Rate diminishes as reaction proceeds
How is shelf life defined in relation to initial concentration of a reaction (hint: to do with time)
Time for reaction to fall to 90% of the initial concentration
- For first-order t90 = 0.105/k1 (Obtained by substituting C=90, C0=100 into first order rate eqn) –> independent of the initial concentration
- For second-order t90 = 0.1 C0 / K0
For a zero-order reaction (kinetics);
A) What conditions are required for it to occur?
B) What is the formula for the rate of reaction?
C) Draw a labeled plot of what concentration against time looks like
D) Gradient? (-k) E
E) Unit of k (rate constant)
A)
Occurs when the rate of reaction is independent of the reactant concentration (no reactants)
B)
- Rate of reaction is constant
- K0 or - (dC/dt)
C)
See attached image (linear relationship between conc and time)
D)
-k
E)
mole L-1 s-1 (s-1)
What type of drug form most commonly exhibit zero-order kinetics? Why does it do this?
Pharmaceutical suspensions
- Drug in solution constantly replenished by suspended drug –> concentration stays the same
When does second-order kinetics occur? Give examples of what it looks like
Occurs when the rate of reaction is proportional to the product of two concentration terms OR to the second power of a single term
A + B –> products
2A –> products
For second-order kinetics;
A) What is the rate equation when the concentration of each reactant is the same?
B) Units of K (rate constant)?
C) Draw a labeled plot of what concentration against time looks like if the concentration of each reactant is the same
See attached image for answers to A, B and C
How to determine the reaction order? (how to know if its zero-order, first-order or second-order)
Clue: 2 ways
Plotting for order –> look for linear result (if linear will be zero-order or second order OR first order LOG)
- C vs t (zero order)
- Log C vs t (first order)
- 1/C vs t (second order)
Half-life method: For a number of different initial concentrations measure the time taken for conc to fall to half ie “half-life”
- Zero order C0/2t1/2 will be constant
- 1st order –> half life will be constant
- 2nd order –> 1/C0t1/2 will be constant
What are pseudo/apparent order reactions? Provide an example of how it works using second-order rate reaction
Reactions proceed at an order that is lower than expected
- DA/dt = k2 [A] [B] = rate of reaction (k2 is second-order rate constant)
- But if the concentration of one reactant is held constant throughout the reaction –> then that concentration term becomes a constant.
> Constant concentration through 1. buffering to maintain pH and 2. one reactant is in excess eg water
- Rate = k2[A][B] becomes k1 [B] where k1=k2[A] (this reaction is said to be pseudo/apparent first=order)
How to get first-order rate constant from second-order rate constant
multiplying second-order rate constant by concentration –> first-order rate constant.
How does a drug in solution (suspension) degrade by 1st order kinetics?
1st order kinetics: Rate = k1[A]
- As it is a suspension, the concentration in solution is replenished by dissolution of suspended drug –> [A] is held constant
Rate = k1[A] = K0 where K0 = k1[A]
- First-order rate constant and concentration of drug have been combined into a single constant K0
How does a reaction go from a third-order reaction to pseudo-zero-order when water is involved?
See attached image
The concentration of water stays the same. [A] wont change in suspension.
summary of parameters for zero order, first order and second order kinetics.
- Linear equation
- Intercept
- Gradient
- Units of k
- Half life (t1/2)
What is the collision theory? What are some factors that affect it?
It is necessary in order for a reaction to occur
- Velocity of impact and orientation of reactants determine whether a reaction takes place
- Which proceeds to a short-lived intermediate that breaks down to produce products
- Increase in reaction rate as temperature increases
What is the transition state theory? What is the difference between this and the collision theory?
This theory is focused on bond breakage rather than collisions
- Collision theories do not fully explain reactions, activation energies do not reflect the energy required to break bonds
- For reaction to proceed to form products, in addition to colliding, must pass through an activated complex called the transition state
- The transition state is at a higher state of energy and is unstable –> breaking down to reform products or reform reactants
