Chapter 12 Measurements of physical properties for drug design in industry

Abstract

Publisher Summary With the emergence of combinatorial chemistry in drug discovery the measurement of physico-chemical parameters for a large number of compounds is required at a much earlier stage of the drug discovery process. The most important physical–chemical parameters are lipophilicity, solubility, acid–base character, and electrochemical redox potential. These properties can be used both in modeling absorption, distribution, and cell permeation, and in the structure-activity relationship correlation to help design active compounds. The solubility parameter becomes crucial in the later stage of drug development such as in formulation. The computer-controlled HPLC with automated sample handling, injection, and computerized data acquisition and processing makes possible the measurement of hundreds of samples per week without too much manual work. The measurements are made by running overnight and at weekends so this requires reliable instrumentation. The value of information as a function of cost and time is more important than applying new scientific approaches immediately. The separation technique can be used in various ways for the measurements of physico-chemical parameters. The more traditional approach is to use the chromatographic technique for the concentration determination necessary to derive the physico-chemical properties.