Introduction

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

“These new compounds, like rocks, never dissolve in water.” It sounds so familiar to you, does it not? Product development scientists often encounter significant difficulties in solving the problem of poor water solubility of drug candidates in the development of pharmaceutical dosage forms (Sweetana and Akers, 1996; Yamashita and Furubayashi, 1998; Willmann et al., 2004; Di et al., 2006). As a matter of fact, more than one-third of the drugs listed in the U.S. Pharmacopeia fall into the poorly water-soluble or water-insoluble categories (Pace et al., 1999). It was reported a couple of decades ago that more than 41% of the failures in new drug development have been attributed to poor biopharmaceutical properties, including water insolubility (Lipper, 1999; Prentis et al., 1988), while it was still indicated recently that about 50% failure of drug candidates was due to poor “drug-like” properties (Hartmann et al., 2006). It is commonly recognized in the pharmaceutical industry that on average more than 40% of newly discovered drug candidates are poorly water soluble. Poor “druglike” properties of lead compounds led to ineffective absorption in the site of administration, which has been designated as an important part of the high clinical failure due to poor pharmacokinetics (Caldwell et al., 2001; Kerns and Di, 2003; Hartmann et al., 2006).