Date post: | 21-Apr-2017 |
Category: |
Health & Medicine |
Upload: | asad-bilal |
View: | 18 times |
Download: | 1 times |
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
5
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
7
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
9
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 ZAZBѴµ
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
27
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 ReactionFirst -Order ReactionSecond-Order ReactionPseudo-Zero-Order ReactionPseudo-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
33
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
Equation
35
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
ApplicationsChemical reactions such as
decomposition of medicinal compoundsProcesses of drug absorption,
distribution and elimination from the bodyShelf 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:
RTaE
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)(
logTRTTTE
kk 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
Kk
Q )10(10
52
53
THANK YOU FOR YOUR ATTENTION