Effect of Cryogrinding on Physico-Chemical Properties of Drugs. I. 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 low temperature grinding (at 78 K). From electron microscopy data, there were determined the form, mean linear sizes of particles and then specific surface was calculated. From X-ray data, a fraction of microcrystalline phase in cryogrinded samples was calculated and it was showed that the intense defect formation process takes place up to partial amorphization at final stage of mechanical treatment. By ultra-violet spectroscopy, the solution behaviour of initial (intact) and activated forms of theophylline was studied. The values of solution rate and solubility for activated forms are 12 and 1.5 times greater accordingly 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 activation were calculated.