Structure of disintegrating pellets with regard to fractal geometry.
OBJECTIVE
The aim of this study was to investigate the influence of the granulation liquid on pellet properties.


METHODS
Pellets containing propyphenazone were obtained by extrusion/spheronization using different 2-propanol/water mixtures as granulation liquids. The pore structure of the pellets was determined by mercury porosimetry. The fractal dimension of the pore system was calculated according to the model of the Menger sponge. Further characterization included SEM-photographs, disintegration, dissolution and tensile strength.


RESULTS
Fractions exceeding 40% 2-propanol in the fluid resulted in rapid dissolution rates of the pellets. This effect was caused by the rapid and complete disintegration of the pellets as compared to those obtained with less 2-propanol in the mixture. These phenomena were interpreted as being due to a change in the particle bonding of the pellets at concentrations of 40% 2-propanol. Evidence for this hypothesis resulted from the spheronization process, the tensile strength measurements and from SEM-photographs. The analysis of the pore system in terms of fractal dimensions implied a dependency of the fraction of 2-propanol in the granulation liquid on the pore structure. High fractions of 2-propanol resulted in lower fractal dimensions close to the dimension of the Menger sponge (2.727).


CONCLUSIONS
The structure of pellets can be markedly influenced by the composition of the granulation liquid. Investigations of the pore system in terms of fractal geometry are more useful for the explanation of pharmaceutical properties than if the pure values for the porosity are taken.
Schröder
M
M
Department of Pharmaceutics and Biopharmaceutics, Christian-Albrechts University of Kiel, Germany.
Kleinebudde
P
P
D000433:1-Propanol / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry; D017709:Fractals; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D011208:Powders; D012995:Solubility; D013718:Tensile Strength
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011208:Powders; D000433:1-Propanol; C009077:propyphenazone; D000983:Antipyrine