Concept of rate of reaction. Factors effecting rate of reaction. Concept of order of reaction. Methods for the determination of order of reaction. Pharmaceutical importance and applications of rate and order of reaction.

1. Rate and Order of Reaction
Asad Bilal
University Of Lahore
Asad.bilal14@gmail.com
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2. Agenda
 Concept of rate of reaction.
 Factors effecting rate of reaction.
 Concept of order of reaction.
 Methods for the determination of order of
reaction.
 Pharmaceutical importance and applications of
rate and order of reaction.
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3. Reaction Rate
 What does “rate” mean ?
 Can you think of an everyday measurement of
rate ?
 How about a car speed in miles per hour!
 How about water flow in gallons per minute!
 How about an audience entering a stadium in
people per hour!
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4. What do all these measures have in
common???
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6. Reaction Rate
 In chemistry, the amount unit may vary but is
often in moles, moles per liter (molarity) grams
or even liters.
 Rates of chemical reactions are most often
measured as moles per second, molarity per
second.
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7. Rate of Reaction
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8. Rate of Reaction
 Reaction rate is the speed at which a reaction
takes place.
 It is “how quickly” a product is formed in a
chemical reaction.
 Example
Mg + Cl2 MgCl2
Reactants Product
 In the case of multiple step reactions the
slowest step determines the rate of reaction.
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9. Collision Theory
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10. Collision Theory
 Reactions take place when reactants bump to
make products.
Mg + Cl2 MgCl2
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11. Collision Theory
 Reaction Rate is how quickly you create a new
substance in a chemical reaction.
 Faster reactions have more collisions.
 Slower reactions have less collisions.
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12. Dependence of Reaction Rate
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13. Factors Effecting Rate of Reaction
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14. Factors Effecting Rate of Reaction
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 Temperature
 Effect of concentration
 Light
 Solvent
 Ionic Strength
 Dielectric constant
 Catalysis

15. Temperature
 Generally, the speed of many reaction can be
increased 2 to 3 times with each increase of
10o
C in temperature.
 The effect of temperature on reaction rate is
given by Arrhenius equation
K= Ae-Ea/RT
 The frequency factor A is the measure of
frequency expected between the reacting
molecules.
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16.  In Logarithm it may be expressed as follow
Log K= log A – Ea/ 2.303RT
 The Arrhenius equation is useful when Ea is in
the range of 10 to 30 Kcal/mole.
 If Ea is only 2 to 3 Kcal/moleas in the case of
photolytic reactions little advantage is gain
from the equation.
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17. Effect of Concentration
 As the concentration of reacting molecules is
increased the no of collisions between the
molecules also increased. Consequently the
rate of reaction is increased.
Concentration Collisions between molecules
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18. Light
 Light energy may be absorbed by certain
molecules which become activated to under
go reaction.
 Most visible light and UV light cause photo
chemical reaction. These reactions do not
depend on temperature.
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19.  However, Once a molecule have absorbed
energy , It may collide with other molecules
raising their kinetic energy resulting in
increase in temperature.
 Examples:
Pharmaceutical compounds which
undergo photo chemical decomposition
include Riboflavin and Phenothiazines etc.
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20. Solvent
 The quantitative relationship between the
reaction rate and the solubility of reactants and
products is given by equation.
Log k= log K0 + V/2.303 R . 1/T (∆SA+∆SB-∆S*)
 In other terms a polar solvent tends to
increase the rate of those reactions in which
product formed is more polar than reactants.
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21.  If the products are less polar then it tends to
decrease the rate of such reactions.
 Commonly used non aqueous solvents for
drugs include Ethanol, Glycerol and
vegetable oil etc.
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22. Ionic Strength
 The effect of ionic strength of a solutionand its
rate of degradation may be expressed as
follows
Log K= log K0 + 1.02 ZAZB µѴ
 According to the above equation an increase
in the ionic strength of solution would tend to
decrease the rate of reaction.
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23. Inverse trend
Ionic Strength Rate of Reaction
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24. Dielectric constant of solvent
 The dielectric constant (or relative permittivity )
of solvent has a significant effect on the rate of
reaction.
 Dielectric constant of an ionic reaction is given
by
Log K= log K ε=∞ - K ZA ZB/ε
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25.  If the reacting ions are of opposite charges
then it will result in increase rate of reaction.
 If ions of similar charges involve in reaction it
will decrease rate of reaction.
Increase in rate of reaction
Opposite Charges Similar Charges
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26. Catalysis
 A catalyst is defined as a substance which
increase or decrease the rate of reaction
without itself being altered chemically.
 Most of the chemical reactions are catalyzed
in the presence of catalyst.
 These enhanced the rate of reaction by
providing an alternative course for chemical
reaction.
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27. Order of Reaction
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28. Order of Reaction
 The order of reaction is defined as the
manner in which the rate
of a reaction varies with the concentration of
the reactants.
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29. Types of Reactions With Respect to their Order
Zero-Order Reaction
First -Order Reaction
Second-Order Reaction
Pseudo-Zero-Order Reaction
Pseudo-First-Order Reaction
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30. Zero-Order Reaction
 In Zero-Order reaction the reaction rate is
independent of the concentration of the
reacting substance or reaction rate depends
on the zero power of the reactant.
 Example
Degradation of solution. When solubility is
the factor , only that amount of drug that is in
solution undergoes degradation.
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31. First-Order Reaction
A reaction is said to be first-order if the
reaction rate
depends on the first power of
concentration of a single reactant.
Example
Decomposition of H2O2 catalyzed
by iodine ions.
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32. Second-Order Reaction
A reaction is said to be second-order if
the reaction rate depends on the
concentration of two reactant species.
Example
Sponification of Ethyl acetate.
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33. 33

34. Pseudo-Zero-Order Reaction
Many drugs, in the solid state,
decompose according to pseudo-zero-
order rates as reactions occur between
the drug and moisture in the solid
dosage form. The system behaves as a
suspension, and b/c of the presence of
excess solid drug, the first-order reaction
rate becomes a pseudo-zero-order rate,
and loss rate is linear with time.
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35. Equation
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36. Pseudo-First-order Reaction
 A pseudo-first-order reaction can be defined
as a second-order or bimolecular reaction that
is made to behave like first-order reaction.
This happens when one reacting material is
present in great excess or is maintained at a
constant concentration compared with the
other substance. Under such circumstances
the reaction does not exhibit a significant
change in concentration during the degrative
reaction.
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37. Example
Hydrolysis of an Ester.
The drug that obeys pseudo-first-
order kinetics is Cefotaxime sodium.
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Pharmaceutical Applications
of Reaction Kinetics

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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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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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Apparent Zero Order Reaction Kinetics
 Suspensions are a special case of zero order
kinetics, in which the concentration of drug in
solution depends on its solubility.
 As the drug in solution decomposes, more of it
is released from a reservoir of suspended
particles thereby making the concentration in
solution constant.
 The effective concentration is the drug
equilibrium solubility in the solvent of
formulation at given temperatures

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Chemical instability
 Can present as;
 Loss of potency
 Accumulation of toxic degradative products
 Degrardation of excipient responsible for product
stability e.g. emulsifying agents, preservatives
 Conspicuous colour change e.g. marked
discoloration of adrenaline although very slight
change in adrenaline content, is unacceptable to
patients, pharmacists, physicians and the nurses.

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Solid state versus solution stability
Generally, chemical reactions proceed
more readily in liquid state than in solid
state
Serious stability problems are more
commonly encountered in liquid
medicines e.g. order of dosage form
stability is generally: solution <
suspension < tablet.

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Determination of Order of Reaction
 Use of rate equation – The data
collected in a kinetic reaction should
be substituted into the integrated form
of equations of various orders.
 The process under test should be
considered to be of that order where the
calculated k value remains constant within
limits of experimental error.

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Determination of Order of Reaction..
 Half life method – For a zero order or pseudo
first order reaction, t ½ is proportional to initial
concentration of reactant (Co),
t½ for a first order reaction is independent of
Co, .
 Graphical method – For a zero order or
pseudo first order reaction, plot of C vs. t is
linear; for first order reaction, plot of log (Co-
Ct) vs. t is linear.

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Factors Affecting Rate of Reactions
 The rate of reaction (degradation of
pharmaceutical products) can be influenced
 temperature,
 moisture,
 solvent (pH, dielectric constant, etc),
 light (radiation),
 catalysts,
 oxygen and
 concentration of reactant (s).

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Temperature
Temperature – Rate of most chemical
reactions increase with rise in
temperature up to 2 to 3 times with each
10° rise in temperature.
The relationship is expressed by
Arrhenius equation:
RT
aE
Aek
−
=

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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
The time required for 10 % of the drug to
degrade with 90 % of intact drug
remaining is based on Arrhenius
equation:
k = reaction rate, T = temperature,
 R = gas constant, Ea = activation
energy
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12
1
2
303.2
)(
log
TRT
TTE
k
k a −
=

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Concept of Q10
Q values of 2 (Ea ≈ 12.2 kcal/mole), 3
(Ea ≈ 19.4 kcal/mole), and 4 (Ea ≈24.5
kcal/mole) are commonly used
They represent the energies of activation
of the reactions around room
temperature.
T
T
K
k
Q
)10(
10
+
=

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