Reaction Kinetics and Drug Stability Reaction...
Transcript of Reaction Kinetics and Drug Stability Reaction...
Reaction Mechanisms
Simple complex
Reaction Kinetics and Drug Stability
Parallel Reversible Consecutive
Kf
A B Kr
K1
K2
A
N P
A B C
K1 K2
Reaction Kinetics and Drug Stability
reactions Kf
A B
Kr
Reversible
Time
C (
mg/
ml)
Reactant
Product
Reversible
Reaction Kinetics and Drug Stability
reactions Kf
A B
Kr
BkAkdt
dArf Integration tkk
AkAkk
Akrf
rrf
f)(
)(ln
0
0
This equation may be simplified by introducing the equilibrium condition: Kf Aeq = kr Beq in which Ao – Aeq = Beq
tkkAA
AArf
eq
eq)(ln
0
t
kk
AA
AA rf
eq
eq
303.2log
0
OR
Reversible
Reversible
Reaction Kinetics and Drug Stability
reactions This equation may be simplified by introducing the equilibrium condition: Kf Aeq = kr Beq in which Ao – Aeq = Beq
tkkAA
AArf
eq
eq)(ln
0
t
kk
AA
AA rf
eq
eq
303.2log
0
OR
eq
eq
AA
AA
0log
t
303.2
rf kk Slope =
kf and kr can be calculated
Slope x 2.303 = kf + kr
equilibrium constant of the reaction:
eq
eq
r
f
A
B
k
kK
Tetracycline undergoes epimerization. At the equilibrium
point a distribution consisted of 32% of tetracycline and
68% of epi-tetracycline was obtained. Measuring the
concentration of tetracycline at different time interval and
plotting the data according to the following equation lead
to a straight line the slope of which equals 0.01 min-1,
calculate both Kf and kr
Reversible
Reaction Kinetics and Drug Stability
reactions
Reversible
Reaction Kinetics and Drug Stability
reactions
kf = 2.1 kr
Slope = 0.01
0.01 x 2.303 = kf + kr
0.01 x 2.303 = 2.1 kr + kr = 3.1 kr
kr = 0.02303 = 0.00767 min -1
3.1
kf = 2.1 x 0.00767 = 0.06 min -1
1.232
68
eq
eq
r
f
A
B
k
kKt
kk
AA
AA rf
eq
eq
303.2log
0
K1
K2
A
N
P
The corresponding rate equation is:
PkPkPkdt
dp 21
k = k1+ k2
P = Po e-kt
Rate of formation of the acidic
product
Pkdt
dA1
kt
o ePkdt
dA 1
)1(10
kt
o ePk
kAA
Neutral product equation )1(2 kt
o ePk
kN
`
ln P = ln Po – kt
)1(1 kt
o ePk
kA
Parallel
Reaction Kinetics and Drug Stability
reactions
Parallel
Reaction Kinetics and Drug Stability
reactions
t
ln p
Slope =- k
(1 - e-kt)
A
oPk
kSlope 1
oP
kxSlopek 1
k2 = K – K1
ln P = ln Po – kt )1(1 kt
o ePk
kA
Consecutive
Reaction Kinetics and Drug Stability
reactions
Rate of decomposition of A
Akdt
dA1
Rate of change in conc. of B
BkAkdt
dB21
Rate of formation of C
Bkdt
dC2
tkeAA 1
0
)( 21
12
10 tktkee
kk
kAB
)(
11 21
12
21
0
tktkekek
kkAC
A B C
K2 K1
Consecutive
Reaction Kinetics and Drug Stability
reactions
First Step is Rate-Limiting Second Step is Rate-Limiting
A B C
K1 K2