The concept of isotonicity in pharmacy arose at the turn of the century from earlier fundamental discoveries. Various approaches to the problem of determining quantities of substances required for the preparation of isotonic solutions that were adopted by pharmacists are discussed in the light of present knowledge. These considerations, some based upon the Arrhenius theory and others representing simple conversion of physical or biological methods, led to the gradual acceptance of the practice of adjusting solutions to conform to certain accepted isotonic values. The basis for choosing certain of these values is presented.
HE APPLICATION of physical chemistry to the problems of the physiologist prior to the 20th century is well summarized in a three-volume monograph by Hamburger (1). Very little theoretical work has been done in the last fifty years to modify the essential concepts of these early workers, but excellent summaries of experimental work relating the osmotic properties of pharmaceutical solutions to physical chemical measurements have been published (2, 2a, 3). Danielli (4) has taken the lead in establishing the difference between animal membranes and ideal semipermeable membranes, and Husa (5) has reported experiments showing that hemolysis of red blood cells is not prevented by certain substances a t concentrations which might be calculated to be isotonic according to the physical chemical definition of isotonicity (6). Modern physiologists have not provided a method of approach to the problem of defining a term to replace isotonicity, and the medical practitioner seems content to accept as isotonic, solutions which are found to have the freezing point of blood serum (--0.53', approximately). Substances like ammonium chloride, boric acid, urea, ethyl alcohol, glycerin, and others that have been reported to offer little or no protection against hemolysis may be regarded as exceptional, but there seems to be little tendency to provide different treatment of these substances in routine pharmaceutical practice.
Since the appearance of Hamburger's work ( I ) , there has been very little fundamental change in the basis for calculating quantities required to produce isotonic solutions. In every case, the calculation is based upon the fundamental concept that the solution should be of such concentration as to exhibit freezing-point