EFFECT OF CRYOGRINDING ON PHYSICOCHEMICAL PROPERTIES OF DRUGS .1. THEOPHYLLINE - EVALUATION OF PARTICLES SIZES AND THE DEGREE OF CRYSTALLINITY, RELATION TO DISSOLUTION PARAMETERS

An activation of crystalline form of theophylline was carried out by l ow temperature grinding (at 78 K). From electron microscopy data, ther e were determined the form, mean linear sizes of particles and then sp ecific surface was calculated. From X-ray data, a fraction of microcry stalline phase in cryogrinded samples was calculated and it was showed that the intense defect formation process takes place up to partial a morphization at final stage of mechanical treatment. By ultra-violet s pectroscopy, the solution behaviour of initial (intact) and activated forms' of theophylline was studied. The values of solution rate and so lubility for activated forms are 12 and 1.5 times greater acccordingly then ones for initial form. On the basis of experimentally determined thermodynamic characteristics of solution process for the initial and activated forms, the thermodynamic characteristics of theophylline ac tivation were calculated.