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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5320_Библиотеки_им_академика_М_И_Перельмана
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k
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126
Pharmaceutical Dosage Forms and Drug Delivery
6.3.1.3.2 Linear Regression I: Double- Reciprocal (Hughes– Klotz) Plot
Inverting Equation 6.11,
d
1θ=+
(6.13)
L
θ
slope as kd
FIGURE 6.8
θ
LL
d
[]
+
[]
k
11
[]
()
[]
()
θθ
dd
[]
=−
kk
yy
yy
//
d
d
y
y
dd
[]
=−
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Complexation and Protein Binding
6.3.1.3.3 Linear Regression II: Scatchard Plot
127
θ can also be converted into:
1
=
(6.14)
Adding and subtracting 1/ kd from this equation:
θ
LL L
[]
1111
=
kkkk kk
=−
k
+−=− −
+
[]
dddd dd
L
+
kk
1
k
d
−
[]
dd
kk
L
d
d
1
=−
k
d
kk
dd
+
[]
L
[]
L+
+
1
L
Or,
1
max
[L]
=−
k
max
kykL
max
k
(6.16)
θθθ
kd and an intercept of y
/ kd
Interchanging the x- and y
plotting θθx- and y
regression assumes that the yx
6.3.2 Thermodynamics of Ligand– Protein Binding
and plotted against the molar ratio of ligand to protein (Figure 6.9
H) of binding, the slope of the
∆∆ ∆GTS=−
∆GRTk=−
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128
FIGURE 6.9
Pharmaceutical Dosage Forms and Drug Delivery
G H S)
G
H
S
kd).
lnd (6.17)
R is the gas constant; T is the absolute temperature.
6.3.3 Factors Influencing Protein Binding
6.3.3.1 Physicochemical Characteristics and Concentration of the Drug
(Figure 6.10
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Complexation and Protein Binding
FIGURE 6.10
129
in vivo
concentration.
drug remains constant.
6.3.3.2 Physicochemical Characteristics and Concentration of the Protein
6.3.3.3 Physicochemical Characteristics of the Medium
protein interactions. In addition, changes in the dielectric constant of the medium, such as in the presence
6.3.4 Plasma Protein Binding
of free drug in the blood declines.
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130
6.3.4.1 Plasma Proteins Involved in Binding
Pharmaceutical Dosage Forms and Drug Delivery
3, the protein comprising 4.0 g of
1.
2.
6.3.4.2 Factors Affecting Plasma– Protein Binding
1. Concentration of free drug
2.
3. Concentration of protein
6.3.4.3 Consequences of Plasma– Protein Binding
1.
albumin, thus affecting their free concentrations in plasma.
2.
of the protein molecules.
3. -
of PPP and a large volume of distribution. Although a drug bound to plasma proteins is not able
replenish the free drug lost from
volume of distribution.
4.
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Complexation and Protein Binding
131
a. -
b.
c.
6.3.4.3.1 Effect on Dosing Regimen
1.
proteins is affected (such as burns).
2.
3.
4.
6.3.5 Drug Receptor Binding
6.3.6 Substrate Enzyme Binding
[]
[]
M
y
[]
[]
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132
Pharmaceutical Dosage Forms and Drug Delivery
v is the initial reaction rate; v
S
vk=
max
(6.18)
+
S
and kM
derivation.
yk=
max
L
d
(6.12)
+
L
Review Questions
6.1
A 3)]SO
4
B 66]
C 3
D 2
E (C)Fe(CO)2
4
2+
3
6.2
A
B Ammonium tetrachlorocuprate(II)
C
D
6.3
A
B
C
D Insulin
6.4
A
B
C
D Covalent bonding
E Ionic bonding
A
B
C
D Covalent bonding
E Ionic bonding
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Complexation and Protein Binding
133
6.6
A Protein concentration
B Drug concentration
C
D
E Rate of binding
6.7
6.8
FURTHER READINGS
Applied Physical
Pharmacy
Remington: The Science and Practice of
Pharmacy
Nat Rev
Drug Discov 3
Physicochemical Principles of Pharmacy
Pharmaceutical Press.
barbital. J Am Pharm Assoc 43
Pure Appl.
Chem. 70
J Pharm Sci 66
MN+→ +
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7
Chemical Kinetics and Stability
LEARNING OBJECTIVES
On completion of this chapter, the students should be able to
1.
2.
3.
4.
Compute the shelf life (t90
6. Describe the log k
7.
8.
7.1 Introduction
susceptible to chemical decomposition in their dosage forms. Degradation can lead to the loss of the
7.2 Reaction Rate and Order
rate of a reaction is the amount or concentration of a degradation product formed or the reactant
rate equation
reaction,
DOI: 10.1201/9781003389378-9
AB
(7.1)
134
−=
11
aCtbCtmCtnCt
d
d
d
AB
C
t
C
t
ab
d
d
d
AB
C
t
C
t
ab
+→ +
d
[]
tt
t
32
dt
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Chemical Kinetics and Stability
a, b, and m, n are the stoichiometric
coefcients (number of moles participating in the reaction) for the corresponding reactant or product,
d
11
d
d
ABM
−= =
d
d
d
d
N
(7.2)
d
CA is the change in the concentration of reactant A over a period of time dt
for all reactants and products in the equation.
d
AB
==− (7.3)
kC C
Or
d
N
M
== (7.4)
kC C
k is the rate constant.
that is, the concentration after a time period, t
t, is higher than the starting concen-
k, is positive in both rate equations.
order
a
respect to reactant B is b, and the overall order of the reaction is a + b.
COOC HNaOHCHCOONa CHOH
325325
dCHCOOC H
325
te
=−
dCHCOONa
=
d
=−
dCHOH
=
dNaOH
d
5
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