ABSTRACT
This chapter discusses the cosolvent effects on solubility and stability, and their use in parenteral products. It presents the theoretical approaches to characterizing solubility in cosolvent systems. For formulating poor water-soluble compounds, use of cosolvent is one of the simplest and most common approaches. The approach is also widely used in the early development phase, as limited information is available for the molecule. The cosolvent approach also allows overcoming dissolution rate limited drug absorption. A quick survey of the literature and pharmaceutical development report suggests that the most commonly used water miscible cosolvents are dimethylacetamide, dimethyl sulfoxide, ethanol, glycerin, polyethylene Glycol 300 and 400, propylene glycol, hydroxyl propyl-beta-cyclodextrin, sulfobutyl-beta-cyclodextrin. In multiuse parenteral products that require the use of a preservative system, studies have shown that preservative effectiveness can be influenced by the cosolvents. Since cosolvents can produce unwanted effects when used parenterally, investigation of other means of solubilizing compounds may be worthwhile if pain, inflammation, or phlebitis is significant.
