ABSTRACT
This chapter explores the theoretical and practical considerations for the use of metastable solids in formulations to gain a solubility or dissolution rate advantage. It suggests experiments that identify the potential solid forms of the drug and elucidates the potential advantages and disadvantages. The chapter covers some specific examples of the degree of enhancement that can be expected and special considerations for each type of solid. It describes the advantages and disadvantages of each type of solid and gives numerous examples from the pharmaceutical literature where alteration of the solid form resulted in increased solubility. Alteration of the solid state phase of the drug substance can influence its solubility and dissolution properties by affecting the solute:solute molecular interactions. Crystalline polymorphs, solvates, hydrates, and amorphous forms of drug substances have been used to change the thermodynamic driving force for dissolution and increase the apparent solubility of poorly soluble drugs.
