Stability of Drugs and Dosage Forms Sumie Yoshioka

2.3. • Stabilization of Drug Substances against Chemical Degradation 129
Figure 122. Stabilization of prostacyclin by increasing concentrations of α -CD ( ) β -CD(∆), and γ -CD( )(pH
7.0, 15°C). (Reproduced from Ref. 524 with permission.)
prostacyclin is stabilized to an even larger extent. 524 This differential stabilizing effect has
been explained by the fact that ionization of the terminal carboxylic acid of prostacyclin
inhibits complex formation. The methylation of the various hydroxyl groups on cyclodextrins
has a variable effect on stability. For example, heptakis(2,3-di-O-methyl)-β -CD (DMβ
-CD) shows a larger stabilizing effect on prostacyclin than does heptakis(2,3,6-tri-
O-methyl)-β -CD (TM-β-CD) (Fig. 123). 525
Prostaglandin E, in neutral and alkaline solutions is destabilized by β-CD but stabilized
by O-carboxymethyl-O-ethyl-β -CD(CME-β-CD) (Fig. 124). 526 This stabilizing effect has
been observed in a fatty alcohol propylene glycol ointment. Dehydration of prostaglandin
E, and isomerization of prostaglandin A 2 are enhanced by β -CD but inhibited by DM- β -CD
and TM-β-CD (Fig. 125). 527 HP-β -CD exhibits an inhibiting effect on degradation only in
the acidic pH region. 528
Stabilization of prostaglandins in the solid state by CDs and their derivatives has also
been reported. The stability of 16,1 6-dimethyl-trans-∆ 2 -prostaglandin E 1 methyl ester
against dehydration and isomerization in the solid state is increased by complex formation
with β -CD. 529 As shown in Fig. 126, the stability of prostaglandin E 1 is decreased by the
Figure 123. Stabilization of prostacyclin by increasing concentrations of TM- β -CD ( ,) β -CD ( ,)and DM-β -CD
(∆ ) (pH 7.0, 15°C). (Reproduced from Ref. 525 with permission.)