ABSTRACT
According to accepted conventions, chemical constructs or molecules are considered drug-like if they adhere to speci›c conditions that impart drug-like physicochemical characteristics. Some of these conditions are exempli›ed by extensively studied drug substances and marketed products. Lipinski’s Rule of Five is a rule of thumb used in drug discovery that evaluates drug-like entities and indicates if a chemical compound with certain physicochemical properties and/or biological activity has attributes that would make it a likely drug candidate in humans. The rule was formulated by Christopher A. Lipinski in 2001, based on the observation that most medication drugs are relatively small, low-molecular-weight compounds with acceptable lipophilicity (Lipinski et al. 2001). However, these rules are pertinent to orally active drugs and may not be indicative for drugs used through other routes of administration. Moreover, in the past decade, a number of molecules that do not adhere to this rule have been approved and evaluated. Although these molecules may or may not be orally active, they have been found to be effective therapeutically when administered by other routes such as parenteral, topical, ocular, and otic routes. Many of these molecules have excellent biological activity but show modest to almost no solubility in aqueous mediums, thus making them poorly bioavailable. To harness their therapeutic activity, a number of approaches have been evaluated and have led to novel drug delivery systems. Nanosuspension is one such system that helps overcome the limitations of poor bioavailability and pharmacokinetic pro›les.
