FRACTAL ANALYSIS OF PHARMACEUTICAL PARTICLES BY ATOMIC-FORCE MICROSCOPY

Purpose. Reliable methods are needed to characterize the surface rough ness of pharmaceutical solid particles for quality control and for fin ding the correlation with other properties. In this study, we used fra ctal analysis to describe the surface roughness. Methods. Atomic force microscopy (AFM) was used to obtain three-dimensional surface profile s. The variation method was used to calculate fractal dimensions. We h ave measured fractal dimensions of four granule samples, four powders, and two freeze-dried powders. Results. A computer program was written to implement the variation method. The implementation was verified us ing the model surfaces generated by fractional Brownian motion. The fr actal dimensions of most particles and granules were between 2.1 and 2 .2, and were independent of the scan size we measured. The freeze-drie d samples. however, showed wide variation in the values of fractal dim ension, which were dependent on the scan size. As scan size increased, the fractal dimension also increased up to 2.5. Conclusions. Fractal analysis can be used to describe surface roughness of pharmaceutical p articles. The variation method allows calculation of reliable fractal dimensions of surface profiles obtained by AFM. Careful analysis is re quired for the estimation of fractal dimension, since the estimates ar e dependent on the algorithm and the digitized model size (i.e., numbe r of data points of the measured surface profile) used. The fractal di mension of pharmaceutical materials is also a function of the observat ion scale (i.e., the scan size) used in the profile measurement. The m ulti-fractal features and the scale-dependency of fractal dimension re sult from the artificial processes controlling the surface morphology.