ABSTRACT
One of the most significant problems facing the pharmaceutical scientist relates to enhancing the solubility of the increasing number of poorly water-
soluble compounds being brought into the development pipeline. This large
number is considered the result of high throughput screening methods, which
tend to focus on the target mechanism at the expense of other desired
properties, such as solubility. In general, poorly water-soluble drugs that
undergo dissolution rate-limited gastrointestinal absorption show an increased
bioavailability when the rate of dissolution is improved (1). A number of
techniques have been utilized to enhance the dissolution rate and potentially
the bioavailability of poorly water-soluble drugs. These techniques include
relatively simple processes such as particle size reduction (2), salt selection
(3), and the use of a cosolvent (3) or surface-active agent (3). Endeavors that
are more scientifically complex have also been attempted with varying degrees of success like the formation of a molecular complex (4) or solid dispersion
(5). The use of a metastable polymorphic form has also been evaluated (6). In
solid dosage form development, the most commonly used technique has been
particle size reduction because it is one of the simplest techniques available to
enhance the dissolution rate, and hence bioavailability, without bringing about
significant polymorphic changes. Because the manufacturing of melt-extruded particulate dispersions, which is the subject of this chapter, utilizes particle
size reduction as a first step, it is essential to discuss in detail the most commonly used size reduction techniques to appreciate the relationships.
