| Crystallinity and physical stability are important in drug solid dosage form development. Warfarin sodium is an anticoagulant which has two solid forms, clathrate and amorphous. The physical stability of the two forms was studied and quantitative results on the hygroscopicity were obtained. The mechanism of the loss of crystallinity at various relative humidities was studied using several techniques, including differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), hot-stage microscopy and x-ray powder diffraction. The compression behavior of the clathrate warfarin sodium before and after milling was described using Heckel plots, where the yield strength can be calculated. The unusual shape in the Heckel plot of milled clathrate warfarin sodium may be due to the generation of a second easier yielding form, which increases with compression pressure. This was confirmed by DSC, TGA and hot-stage microscopy. The crystallinities of sucrose and warfarin sodium were quantitatively determined by solution calorimetry. The technique was developed by taking advantage of the energy difference between the crystalline and amorphous forms. The dissolution process for most crystalline material is endothermic, and it is often exothermic for amorphous material, except for complex systems, such as clathrates. The linear relationship between the heat of solution and crystalline material present in the sample provides a simple and convenient way to accurately examine the crystallinity of the material in such formulations, providing no chemical interaction between the drug and its excipients occur and the heat of solution of both the drug and its excipients are known. The method is also valuable in examining the solid state conversion processes. |
