Background
In the process of tabletting medicine, compression force sometimes causes unfavorable changes, such as a chemical reaction between active ingredients and additives, dehydration, polymorphic transformation of the active ingredients, etc. There are strong demands to quickly determine the amounts of polymorphic impurities and to determine whether the crystal system of the active ingredients is maintained while at the same time preserving the the shape of tablets. The parallel beam transmission method of general-purpose XRD system is a highly effective method to observe the change of the crystal system and the degree of change without grinding the tablets. Low levels of polymorphic impurities of active ingredients in a tablet are detectable in a few minutes, even if the content is on the order of 1 wt%. Polymorphic impurities at levels of less than 0.5 wt% are quantitatively detectable when only the pharmaceutical ingredients are measured.
Investigation
Theophylline monohydrate was added to theophylline anhydride as a dummy polymorphic impurity. A standard excipient (lactose/starch mixture) was added at a ratio of 1 to 2 by weight. The mixture was formed into tablets 3 mm thick and 6 mm in diameter. X-ray diffraction measurement was then performed with the transmission arrangement using Rigaku's Ultima IV multipurpose 
diffraction system. As shown in the figure, even if 1 wt% of monohydrate (0.3 wt% of the total weight of the tablet) was contained in the medicinal ingredients, it was successfully detected with measurement of about nine minutes. (X-ray generator output: 50 kV, 300 mA)