THE INFLUENCE OF HUMIDITY TOWARDS THE POLYMORPHISM TRANSFORMATION OF ANHYDROUS THEOPHYLLINE FORM II AND FORM I
Background and objectives: Anhydrous theophylline is known to have four polymorphic forms, Form I, II, III and IV. Different polymorphism will give different stability profile. The aim of this research is to obtained theophylline Form II and I by heating mechanism and to observe the polymorphic Form II and I after being induced by different humidity. Method: Form II and I of anhydrous theophylline were prepared by heating at the temperature of 100°C and then at 267°C. Powder X-ray Diffractometry (PXRD) used to characterize the anhydrous theophylline raw material, Form II and I, analyze the pure and also to observe the polymorphic changes that is influenced by relative humidity. Differential Thermal Analysis (DTA) is used to determine the melting point and the temperature of the polymorphic transformation. Scanning Electron Microscope is used to determine the crystal habits, surface morphology and also the particle size of ahydrous theophylline Form IT and I. Water content is analyzed by using loss on drying method. The relative humidity of 74, 82 and 96% used to induced anhydrous theophylline Form II and I for total of three weeks during storage that will be observe on the third day, first, second and third week. Result: Diffractograms shows that Form I is faster to have development of new peaks compare to Form II. The higher the RH, the greater the development of new peaks. The end product shows the high concentration of theophylline monohydrate. Based on thermogram of DTA, Form II remains at the melting point range of 270 to 274°C while Form I shows the melting point of 279°C. Both induced Form II and I show development of two new endothermic peaks. The surface morphology show both Form II and I have rough surface and both increased in particle size as the duration of induced and the relative humidity increased. The determination of water content shows increase of water content in both samples. However, Form I have the tendency to adsorb more water content compare to Form II. Conclusion: It is proven that Form II is much stable compare to Form I at room temperature as Form II has a lower tendency to adsorb water compare to Form I during storage of three different relative humidity. Diffractogram shows that the high concentration of theophylline monohydrate obtained at the end product.