Injectable Formulations of Poorly Water-Soluble Drugs
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 activit
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Injectable Formulations of Poorly Water-Soluble Drugs Youssef W. Naguib, Hannah L. O’Mary, Zhengrong Cui, and Alan B. Watts
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. Keywords Injectable drugs • Tonicity • Sterility • Drug product stability • Target product profile (TPP) • Intravenous • Intramuscular • Subcutaneous • Intrathecal • Intra-articular • Buffer systems • Cyclodextrins • Surfactants • Emulsions • Liposomes
Y.W. Naguib (*) • H.L. O’Mary (*) • Z. Cui • A.B. Watts (*) Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 2409 University Ave, Austin, TX 78712, USA e-mail: [email protected]; [email protected]; [email protected]; [email protected] © American Association of Pharmaceutical Scientists 2016 R.O. Williams III et al. (eds.), Formulating Poorly Water Soluble Drugs, AAPS Advances in the Pharmaceutical Sciences Series 22, DOI 10.1007/978-3-319-42609-9_6
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Introduction
Injectable formulations encompass a wide range of uses and routes of administration. Although sometimes less preferred due to patient compliance and strict production requirements, injectable formulations are critically important in a variety of indications, particularly in the acute care setting. By direct administration to systemic circulation or target tissue, injectable formulations reduce inter/intra subject variability, allow for rapid onset of action, and enable greater control of pharmacokinetics. The U.S. Department of Health and Human Services lists key medications for use in adult acute care, almost all of which are
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