Chemistry Reference
In-Depth Information
1
INTRODUCTION TO
AMORPHOUS SOLID
DISPERSIONS
1
and Ann Newman
2
1
University of Wisconsin-Madison, Madison, WI, USA
2
Seventh Street Development Group, Lafayette, IN, USA
George Zogra
1.1 INTRODUCTION
Over the years one of the major goals of synthetic chemists has been to provide the
crystalline form of any active pharmaceutical ingredient (API) being introduced into
pharmaceutical development. This is primarily because the symmetrical three-dimen-
sional long-range order and the relatively tight packing of molecules in a crystal lattice
most often ensure a high level of chemical purity and solid-state stability. At the same
time, an API being developed for oral administration in a solid dosage form generally
requires suf
cient aqueous solubility upon contact with
in vitro
and
in vivo
dissolution
media in order to obtain optimal rates of dissolution and acceptable oral bioavailability.
The importance of aqueous solubility in affecting dissolution rates can be shown with the
classical Noyes
-
Whitney equation [1]:
d
C
=
d
t
k
D
A
C
s
C
t
;
(1.1)
where d
C
/d
t
is the dissolution rate,
k
D
is the dissolution rate constant (dependent on the
stirring rate and the diffusion constant),
A
is the total surface area of the drug particles,
C
s
