Chemistry Reference
In-Depth Information
Figure 11.13.
Predicted (regression line) versus observed (solid data points) formation of
epimer in tablets in traditional ICH stability studies.
Figure 11.14.
Predicted design space for epimer as a function of tablet water content and
excipient impurity level with tablet storage at 25
°
C for 24 months and 30
°
C for 12 months from
the “
T
“T/RH” stability study.
Based on the regression model described above, the allowable tablet water content level
can be calculated for a target impurity level of the excipient (100 ppm). Two limiting
cases were examined: (1) constant tablet moisture (corresponding to moisture-
impermeable packaging), and (2) increasing tablet moisture (corresponding to mois-
ture-permeable packaging). A 24-month shelf life at 25
C/60% RH for drug product was
assumed, as well as the backup accelerated condition of 12 months at 30
°
C/65% RH.
°
first case (impermeable packaging), a maximum tablet water content of 2.4%
must be maintained to keep epimer growth below 2.0% during a 24-month shelf life of
drug product with storage at 25
For the
C/60% RH (Figure 11.14). To limit epimer growth to a
maximum of 2.0% at the accelerated condition (30
°
C/65% RH for 12 months), a lower
tablet water content is required, about 2.1%. Based on manufacturing process capability,
°
