Rate and order of reaction

Rate and Order of Reaction
Asad Bilal
University Of Lahore
Asad.bilal14@gmail.com
1

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.
2

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!
3

What do all these measures have in
common???
4

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.
6

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.
8

Collision Theory
 Reactions take place when reactants bump to
make products.
Mg + Cl2 MgCl2
10

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.
11

Dependence of Reaction Rate
12

Factors Effecting Rate of Reaction
13

Factors Effecting Rate of Reaction
14
 Temperature
 Effect of concentration
 Light
 Solvent
 Ionic Strength
 Dielectric constant
 Catalysis

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.
15

 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.
16

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
17

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.
18

 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.
19

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.
20

 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.
21

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.
22

Inverse trend
Ionic Strength Rate of Reaction
23

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
24

 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
25

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.
26

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.
28

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
29

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.
30

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.
31

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.
32

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.
34

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.
36

Example
Hydrolysis of an Ester.
The drug that obeys pseudo-first-
order kinetics is Cefotaxime sodium.
37

38
Pharmaceutical Applications
of Reaction Kinetics

39
KINETICS
Applications
Chemical reactions such as
decomposition of medicinal compounds
Processes of drug absorption,
distribution and elimination from the
body
Shelf life determination.

40
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.

41
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.

42
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

43
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.

44
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.

45
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.

46
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.

47
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).

48
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
−
=

49
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?

50
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
21
12
1
2
303.2
)(
log
TRT
TTE
k
k a −
=

51
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
+
=

53
THANK YOU FOR YOUR ATTENTION

Rate and order of reaction

More Related Content

Rate and order of reaction