Chemistry Reference
In-Depth Information
5
PHYSICAL STABILITY AND
CRYSTALLIZATION INHIBITION
Lynne S. Taylor
Purdue University, West Lafayette, IN, USA
5.1 INTRODUCTION
In order to successfully utilize amorphous solid dispersions (ASDs) to enhance drug
delivery, it is essential to maintain the amorphous form of the drug during the
manufacturing process and the shelf life of the formulated product. In addition, following
oral delivery, the amorphous matrix will hydrate and the drug will dissolve. If the drug
crystallizes within a short time frame upon exposure to biological
fluids, it is clear that the
solubility advantage of the amorphous formulation will not be realized. Therefore, it is
essential to evaluate the crystallization tendency of the drug exposed to different
environmental conditions and to develop strategies to modify crystallization kinetics
through the addition of crystallization inhibitors; for pharmaceutical systems, polymers
are the most widely used crystallization inhibitors. In this chapter, crystallization in the
solid state will be discussed initially, including a consideration of the role of temperature,
residual water, and additives. Subsequently, phase behavior during dissolution of an
amorphous formulation will be explored. Figure 5.1 shows an overview of the factors
that need to be understood and controlled for successful formulation of an amorphous
solid dispersion.
