Stability of Drugs and Dosage Forms Sumie Yoshioka

2.2. • Factors Affecting Chemical Stability 43
where [P] e , is the concentration of product formed at equilibrium. A similar equation is
derived for the case of [D], = /[A] 0 and is used to describe the interaction of isoniazid and
reducing sugars, as shown in Fig. 10. 251
2.2.3.1.e. Pseudo-First- and Pseudo-Second-Order Reversible Reactions
Equation (2.27) represents the rate of reversible conversion of drug D to products P 1 and
P 2 . When [P 1 ] 0 = [P 2 ] 0 = 0 at t = 0, Eq. (2.27) can be integrated to give Eq. (2.28).
(2.27)
(2.28)
The loss of hydrochlorothiazide follows this model, 252 although a complicated mechanism
including multiple reaction steps has been proposed for its degradation. 253
2.2.3.1.f.
Pseudo-First-Order Consecutive Reactions
Equations (2.29) and (2.30) represent the case when drug D converts to P 1 , which is
subsequently converted to P 2 according to consecutive pseudo-fist-order reactions.
(2.29)
Figure 10. Time course of reaction of isoniazid with various reducing sugars under second-order reaction
conditions (pH 1.8, 37°C). , Galactose; X, lactose; O, glucose; ∆, maltose. (Reproduced from Ref. 251 with
permission.)