Depth Profiling of Compression-Induced Disorders and Polymorphic Transition on Tablet Surfaces with Grazing Incidence X-ray Diffraction

Abstract

The importance of induced crystal disorders like crystallite size, crystal defects, and amorphicity with respect to the dissolution rate of the drug has been discussed in many cases. Thus, the characterization of these properties is of great importance in the pharmaceutical formulation development, although the exact correlation between disorders and dissolution rate is still unclear. The aim of this study was to analyze pharmaceutical tablets with grazing incidence X-ray diffraction, which enables the depth profiling of the crystallographic properties of the tablets. To study and clarify the potential of grazing incidence diffraction in the analysis of pharmaceutical materials, the effect of the compaction process on the surface of tablets was examined. Carbamazepine, tolbutamide, and chlorpropamide tablets, compacted using different compression pressures, were studied using grazing incidence angle X-ray diffraction. The effects of compression on the crystallographic properties were investigated as a function of the distance from the tablet surface. The surfaces of the tolbutamide and chlorpropamide tablets were disordered due to the compression. The manifestation of the disorder was deduced to be due to amorphicity, small crystallite size, and amount of crystal defects. The changes were mainly on the surface and diminished strongly as a function of the distance from the surface of the tablet. Moreover, the changes were dependent on the compression pressure used. The changes on the surface of the carbamazepine tablets were also due to the compression but these changes were not clearly dependent on the depth nor the compression pressure. The partial phase transition took place in the chlorpropamide tablets due to the compression. The magnitude of the transition was not highest on the surface because amorphization and texturization also took place on the tablet surface during the compression. The present study proved that grazing incidence X-ray diffraction is a potential novel research tool to reveal crystallographic transformations taking place on the surfaces of the tablets induced, for example, by compression pressure.