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The systematic development of drugs is not new. This is shown by Withering's endeavour, 200 years ago, to make a useful therapeutic agent out of the digitalis plant. Today the way from idea to drug is long, taking about 10 to 15 years, and very expensive. A selection of approaches to drug discovery is described and illustrated with a practical example, the development of isradipine. In this example emphasis is placed on tissue selectivity, which even today remains an interesting research problem. One of the theories, suited to explain tissue selectivity, is also exposed.

The biopharmaceutical factors, which influence the interaction between dosage form and drug activity, extend from the mode of application, through chemical and physical properties of the active constituent, to the final product, including the excipients and manufacturing processes involved. In recent years, important strides have been made in this field, which improve drug safety. This has consequently influenced and enlarged the present scope of pharmaceutical technology drug research.

In this paper the determination of bromine as represented in the literature is briefly reviewed with the matrix and background effects being considered. The results obtained in determining low contents of bromine in pharmaceutical substances of light matrix (Z less than or equal to 8) by the use of a wavelength dispersive X-ray fluorescence spectrometer VRA-20 have shown the sample thickness to influence the Br-Ka radiation. The calibration of a chloroorganic matrix is performed with a so-called substitute standard substance consisting of cellulose and ammonium chloride, which is advantageous, if standard material free of analyte is difficult to get or only small amounts of sample are available. Additional measurements have been carried out to determine chlorine also by the use of a vacuum-tight liquid cell. Detection limits of 3 ppm Br (10 ppm Cl) in a light matrix and of 60 ppm Br in a chloroorganic matrix can be obtained without analyte enrichment by the powder-compressing process. The present possibilities of measuring the F-Ka radiation in active pharmaceutic substances are discussed.

Three concepts for the synthesis of biologically active compounds are discussed and illustrated by examples. In addition to the accidental finding of biologically active compounds, synthesized purely for chemical reasons, analogy models can serve as guidelines for synthesis. In the latter, naturally occurring or synthetic biologically active molecules are modified to optimize or alter the biological properties. A third approach for the synthesis of active substances is oriented according to the side of action. Models from biochemistry and molecular biology serve as a basis for synthesis planning.

The use of spectroscopic methods (IR, NMR, MS) for the investigation of drugs is demonstrated. Due to the high sensitivity mass spectrometry in combination with glass capillary gaschromatography seems to become in many cases the method of choice. The use of computers which are able to determine with the aid of key fragments partial structures of unknown metabolites will be a very promising technique in the the future.

Numerous computer programs have gained entry into drug research; some of them are already used as a matter of routine, whereas others are still being tested. The special advantages of the use of computer programs are shown for the two fields "computer-assisted synthesis planning" and "quantitative structure-activity relationships". Several aspects of cooperation between man and computer are briefly discussed.

Starting from historical examples of the application of models in scientific research, the author treats the present significance of this working method in pharmacy. A short description of various types of models and of the definition of the term "model" is followed by an outline of the major aspects to be considered in using models. The different steps of model elaboration, the requirements to be considered with model elaboration as well as questions concerning the analogy, main properties, goals and limitations of models, and the validity of the results obtained are briefly dealt with and illustrated by examples.