Amity Institute of Pharmacy

Reaction kinetics

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KINETICS Amity Institute of Pharmacy

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KINETICS Amity Institute of Pharmacy

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KINETICS Amity Institute of Pharmacy

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KINETICS Amity Institute of Pharmacy

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KINETICS Amity Institute of Pharmacy

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KINETICS Amity Institute of Pharmacy

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 Shelf life determination Amity Institute of Pharmacy

• 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 Amity Institute of Pharmacy

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 Amity Institute of Pharmacy

• 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 Amity Institute of Pharmacy

• n=1 and the reaction rate is dependent on the

concentration of one of the reactants in the
formulation.
• dC
  kC
dt
• C is the concentration remaining un-
decomposed, unabsorbed, yet to be
distributed, metabolized or excreted at time t
as the case may be
• k is the first order rate constant.
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 First Order Kinetics (cont.) Amity Institute of Pharmacy

• On integration, the equation above

gives:
ln C  ln Co  k t  0
• On rearrangement and conversion to log
in base 10:
kt
log C  log Co 
2.303
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Log concentration versus time Amity Institute of Pharmacy

Log
Conc Slope = -k/2.303
.

Time

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 Exercises?? Amity Institute of Pharmacy

• Determine the expression for rate

constant, k
• Determine the expression for process
half-life, t1/2
• Write the exponential forms of the
equation in natural log and log in base 10.
• What is the significance of process half-
life?
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 Zero order reaction Amity Institute of Pharmacy

• In this type of reaction, n=o and the

reaction rate is independent of the
concentration of the reacting substance.
• The rate of change is constant.
• Here, factors other than concentration of
reactants constitute the limiting factor
e.g. solubility or absorption of light
(photochemical reactions).
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 Zero order reaction (cont.) Amity Institute of Pharmacy

• 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.) Amity Institute of Pharmacy

• Zero order Equation:

 dCo
k
dt

• Co= original concentration of reacting

material, k=reaction rate constant, dt=
change in time.

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 Zero order processes Amity Institute of Pharmacy

• Expression of zero order equation:

•
C  C  kt
t o

• 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
Amity(Zero-
Institute of Pharmacy

order plot)

Conc
Slope = -k0

Time

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 Reaction half-life (Zero-order)
Amity Institute of Pharmacy

• For a zero order reaction, the time for

50% reaction, t½, is given as:
1 Co C o
2
t1 / 2  
ko 2ko

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 Apparent Zero Order Reaction
Amity Institute of Pharmacy

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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 Apparent Zero Order Reaction
Amity Institute of Pharmacy

Kinetics (Cont.)
• Ordinarily, the equation for
decomposition is first order:
 d C 
 k C 
dt
• C=the conc. of drug remaining un-
decomposed at time t
• k=the known first order rate constant.

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 Apparent Zero Order Reaction
Amity Institute of Pharmacy

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 23
 Solid state versus Amity Institute of Pharmacy

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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 Chemical instability Amity Institute of Pharmacy

• 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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 Determination ofAmity Institute of Pharmacy
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 of Pharmacy
Amity Institute

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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 References Amity Institute of Pharmacy

• Physical Pharmacy by Alfred Martin,

Sixth edition

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