Chemistry Reference
In-Depth Information
2.4.5 Performance of ASDs
Solubility enhancement of a poorly soluble drug is frequently accepted as a route to
improved bioavailability of that drug and thus a number of techniques for solubility
enhancement have been developed. While these methods have proven improved disso-
lution compared with the native species, the permeability of the drug through the intestinal
membrane is often overlooked [99]. Interplay between solubility and permeability in
which the increase in solubility corresponds with a decrease in permeability has been
demonstrated for cyclodextrin complex solubilization [100], micellar solubilization [101],
and cosolvent solubilization [102]. The implication of the trade-off between solubility and
permeability is that an increase in solubility may not translate to increased bioavailability
of the drug. Miller et al. found that amorphous solid dispersions of progesterone with
HPMCAS showed an increase in apparent solubility without a change in perme-
ability [99]. The increase in apparent solubility thus resulted in an increased
ux across
the membrane and improved bioavailability [99], a distinct advantage for ASDs over other
solubility-enhancing technologies as demonstrated in Figure 2.17.
Figure 2.17.
Dispersions of
HPMCAS with progesterone
compared with solubilization of
progesterone with surfactant,
cyclodextrin, and cosolvent
demonstrating that (a) the
permeabilityof theASD is constant
over an increasing apparent
solubility and (b) the
ux across the
membrane increases with
apparent solubility. (Adapted from
Ref. 99.)
