Injectable Formulations of Poorly Water-Soluble Drugs

Abstract

Each year, an increasing number of new molecular entities are characterized as having poor water solubility. For parenteral formulations, it is exceptionally important that solubility limitations are well understood so that the desired therapeutic activity can be achieved. Formulation approaches should be implemented to overcome the challenges of solubility for these new compounds. Techniques such as pH manipulation, salt formation, cosolvent or surfactant addition, or complexation may be used to increase aqueous solubility. Advanced techniques focused on increasing drug therapy through delivery of a stabilized dispersion can also be implemented. Formulations such as liposomes and nanosuspensions have been used to promote drug targeting, alter pharmacokinetics, and reduce toxicity without directly increasing molecular solubility. This chapter provides an overview of current formulation approaches used for injectable drugs and also covers advanced approaches in development. Considerations that are specific to injectable products will be reviewed first including buffering, tonicity, sterility, drug product stability, and manufacturing, before detailing formulation strategies used to formulate poorly water soluble compounds. The current authors would like to thank and acknowledge the significant contribution of the previous authors of this chapter from the first edition. This current second edition chapter is a revision and update of the original authors’ work.