Chemistry Reference
In-Depth Information
Figure 11.15.
Summary of model predicting the effect of storage condition on tablet water
content and epimer growth for moisture-impermeable packaging and packaging with
maximum moisture permeability.
a tablet water content of 1.5% at release is believed to be achievable, so for this limiting
case (impermeable packaging) epimer growth would be limited to
2.0%.
For the second case (permeable packaging), moisture vapor transmission rate (MVTR)
calculations were performed to determine the maximum package permeability that would
maintain
2.0% epimer growth during 24 months storage of tablets at 25
<
C/60% RH. In
this scenario, the initial tablet water content is assumed to be 1.5%. For storage at 25
°
C/
60% RH for 24 months, the packaging MVTR must be below 0.149mg/day/tablet
(Figure 11.15). With this permeability, the tablet water content increases during storage
from1.5 to 2.8%. The accelerated condition is more stringent, and, at 30
°
C/65%RH for 12
months, the maximum MVTR is 0.137mg/day/tablet, corresponding to an increase in
tablet water content during storage from 1.5% to a little less than 2.5%.
From this analysis, the maximum tablet water contents at release (1.5%) and on
stability (2.5%) are de
°
ned. Also, the primary container closure system must have a
maximum MVTR of 0.137mg/day/tablet based on the more stringent requirement.
11.4 CONCLUDING REMARKS
Over the past two decades, the pharmaceutical industry has made signi
cant progress on
the drug discovery and design front that has yielded a number of potential drug
candidates with poor or limited solubility and hence limited bioavailability. Solid
dispersions are currently considered an effective method to solve the low bioavailability
problem of poorly water-soluble drugs, but decades of research has only resulted in a
handful of marketed drug products (Table 11.1). The primary challenges in developing
solid dispersions as a drug delivery technology are technical challenges related to method
