Poor Solubility- Where Do We Stand 25 Years afterthe'Rule of Five'?

摘要

It is clear that medicinal chemists have moved beyond the 'Rule of Five' paradigm. With the advent of combinatorial chemistry and high-throughput screening, there has been an increase in the number of poorly water-soluble drug development candidates. The different methods for enhancing dissolution and bioavailability of such drug candidates have been reviewed. Methods are available for the formulation of most small molecule poorly water-soluble drugs as immediate release oral solid dosage forms. Identification of the optimum bioavailability enhancement method will depend on the properties of the drug molecule, the dose and the target patient population. The formulation scientist has to balance the advantages and disadvantages of the different formulation technologies as they apply to the particular drug development project. The choice of dissolution method will also be important.