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Reaction Kinetics
Reaction Kinetics
By
A. S. Adebayo, Ph. D.
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KINETICS
Applications
Chemical reactions such as
decomposition of medicinal
compounds
Processes of drug absorption,
distribution and elimination from the
body
Shelf life determination.
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Shelf life determination
In determining the shelf life of a preparation,
tests are carried out on the active ingredient,
the additives and the finished product to
determine:
Whether decomposition will occur
The type of decomposition
Factors that affect the rate of decomposition
such as light, air, moisture, temperature, etc.
The influence of formulation additives
The rate at which breakdown occurs.
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Rate of Reaction
Expressing speed of a reaction:
as the decrease in concentration of any reacting
substance
as the increase in concentration of the product per
unit time.
If C is the concentration, then the rate of
reaction:
dC
C n
dt
where n=0,1 or 2 for zero, first & second order
reactions respectively
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Order of Reaction
Manner in which the rate of reaction
varies with the concentration of the
reactants
Most processes involving ADME can be
treated as first- order processes
Some drug degradation processes can
be treated as either First or zero order
processes
Some drug substances obey Michaelis-
Menten kinetic process
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First Order Kinetics
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First Order Kinetics (cont.)
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Log concentration versus time
Log
Conc Slope = -k/2.303
.
Time
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Exercises??
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Zero order reaction (cont.)
When solubility is the limiting factor, only
the proportion of drug in solution
undergoes degradation:
As the drug is consumed in the degradative
reaction, more drug goes into solution until
all solid (C) has reacted.
Until this has happened, the degradation
process will not be dependent on the total
conc. of drug but on the proportion in
solution, thereby producing a zero order
process.
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Zero order reaction (cont.)
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Zero order processes
Ct Co kt
Ct=conc. at time t, Co=conc. at time o.
Plot of C against t gives a straight line
with slope of -ko
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Concentration versus time (Zero-
order plot)
Conc
Slope = -k0
Time
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Reaction half-life (Zero-order)
ko 2k o
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Apparent Zero Order Reaction
Kinetics
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Apparent Zero Order Reaction
Kinetics (Cont.)
Ordinarily, the equation for
decomposition is first order:
d C
k C
dt
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Apparent Zero Order Reaction
Kinetics (Cont.)
When concentration is rendered constant
by suspended particles offering
replacement, then
k C ko
thereby turning the first order rate law
into; d C
ko
dt
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Chemical instability
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Solid state versus solution stability
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Determination of Order of Reaction
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Determination of Order of Reaction..
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Factors Affecting Rate of Reactions
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Temperature
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Arrhenius equation
Log transformation gives:
Ea 1
log k log A
2.303 RT
k is the rate of reaction
A is a constant known as the frequency factor
Ea is the activation energy,
R is the gas constant (1.987 calories deg-
1mole-1 OR 8.314 J mole-1)
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Arrhenius equation….
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Activation Energy: Arrhenius
Equation
The degradation of a new cancer drug
follows first-order kinetics and has
degradation rate constants of 0.0001 H-1
at 60 ºC and 0.0009 H-1 at 80 ºC. What is
its Ea?
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Stability Projection for Shelf Life
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Concept of Q10
k (T 10)
Q10
KT
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Concept of Q10…..
Q10 estimates can be t 90 (T1 )
made with the equation: t 90 (T2 ) T
where t90T2 is the Q10 10
estimated shelf life
t90T1 is the shelf life at a
given temperature
∆T is the difference in
temperature between T1
and T2 (i.e. T2 – T1)
Increase in ∆T will
decrease shelf life while
a decrease in ∆T will
increase shelf life
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Shelf-life Prediction
Shelf-life at different storage temperature can
be estimated as:
t 90 (T1 )
t 90 (T2 ) T
Q10 10
t90T2 is the estimated shelf life
t90T1 is the shelf life at a given temperature
∆T is the difference in temperature between T1
and T2
Increase in ∆T will decrease shelf life while a
decrease in ∆T will increase shelf life
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TUTORIAL QUESTIONS
1 An ophthalmic solution has a shelf life of 6
hours at room temperature (25 °C).
Calculate the estimated shelf-life in a
refrigerator (5 °C)
2 An antibiotic has a shelf life of 48 hours in
the refrigerator (5 °C). What is its estimated
shelf-life at room temperature (25 °C)?
3 In what ways can chemical instability be
manifested on formulated products? List and
discuss four main types of reactions involved
in chemical degradation.
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TUTORIAL QUESTIONS
4. A drug suspension (125 mg/ml) decays by zero-order
kinetics with a reaction rate constant of 0.5 mg/ml/hr.
What is the concentration of intact drug remaining
after 3 days?
5. How long will it take for the suspension in question 4
above to reach 90 % of its original concentration?
6. An ophthalmic solution of a mydriatic drug present at
5 mg/ml concentration exhibits first order degradation
with a rate of 0.0005/day. How much drug will remain
after 120 days? How long will it take for the drug to
degrade to 90 % of its original concentration?
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TUTORIAL QUESTIONS
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TUTORIAL QUESTIONS
8. Analysis of the rate of ºC K
degradation of a
colourant in a multi-sulfa
drug preparation shows
40 0.00011
the following results:
Assuming a first- 50 0.00028
order process,
compute the 60 0.00082
activation energy and
the value of K at 25
ºC 70 0.00196
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THANK YOU FOR YOUR
ATTENTION
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