Stability of Drugs and Dosage Forms Sumie Yoshioka

64 Chapter 2 • Chemical Stability of Drug Substances
Table 4.
Continued
Drug hydrolysis E a (kcal/mol) PH a Reference
Racemization and epimerization
Etoposide 18.2 f 11.04 156
Hetacillin 21.2 OH – 163
Epinephrine 23.19 H + 158
Cefsulodin 27.0 9.0 166
Pilocarpine 28.48 OH – 37
Dehydration
Prostaglandin E1 18 1.2 142
24 8 142
Isomerization
Amphotericin B 16.4 7 148
Prostaglandin E1 20 8 142
Decarboxylation
Etodolac 26 H + 170
Oxidation
Ascorbic acid 7.8 6.60 119
12.2 3.52 179
Morphine 22.8 6 202
Procaterol 34.5 6.0 184
a
H+, Hydronium ion-catalyzed reaction; OH-, hydroxide ion-catalyzed reaction.
b Activation enthalpy ∆Η ‡ .
cValue reported in the reference (68 kJ/mol) has been converted to kilocalories per mole.
d Value reported inthereference (95.9 kJ/mol) has been converted tokilocalories permole.
e
Valuereportedin the reference (102 kJ/mol) hasbeenconverted to kilocalories permole.
f Value reported in the reference (76 kJ/mol) has been converted to kilocalories per mole.
So-called Arrhenius plots in which the logarithm of rate (rate constant) is plotted against the
reciprocal of absolute temperature (degrees kelvin) have been used to validate the conformity
of the degradation rates of various drugs to this equation. Linear Arrhenius plots were
reported for the degradation of penicillin G (Fig. 30), 300 the discoloration of a liquid
Table 5. Effect of a 10°C Temperature Change
(20°C to 30°C) on the Relative Degiadation Rate
Constants for Drugs Having Different E a Values
E
k
a
T2/
k T1
(cal/mol)
(T1= 20°C, T2 = 30°C)
10,000 1.76
15,000 2.34
20,000 3.11
25,000 4.12
30,000 5.48