Solution Rate of Theophylline Salts and Effects from Oral Administration

Abstract

The solution rate of several theophylline salts was determined in buffer solutions covering a range of hydrogen ion concentrations somewhat greater than those to which the salts would be exposed after oral administration. It was found that marked differences existed in the rate with which the several salts dissolved and the rates were relatively independent of buffer pH. It was suggested that the fundamental reason for differences found by clinical workers in comparing blood levels from oral administration of the choline and isopropanolamine salts with the ethyl-enediamine salt was due to differences in solution rate. The in vitro solution rates determined strongly support this explanation. The effect of solution rate on maximum blood level and rate of build-up of blood level with time was discussed by means of a mathematical model relating blood level with solution rate and elimination rate from the blood stream. The solution rate of theophylline in acidic and basic media was determined and found to vary inversely with the hydrogen ion concentration of the diffusion layer. A relationship was developed between solution rate of theophylline and diffusion layer pH and it was shown to be capable of roughly predicting solution rate of salts from measurement of this pH.