The sintering of ibuprofen
Abstract
The compression behavior of ibuprofen was characterized and the effect of temperature and heating time on the resulting compacts were also determined. Observed changes in compact tensile strength and compact pore size and volume were consistent with a sintering mechanism. The compression behavior of ibuprofen was characterized by using the Heckel relationship. The Heckel plot for ibuprofen exhibited a continuous curvature which was attributed to plastic deformation and asperity melting as well as the subsequent resolidification of ibuprofen during powder compression. Both the heat of fusion and heat of solution of ibuprofen resolidified from melts were significantly lower than those of the original powder. The heat of solution of ibuprofen compacts was also shown to decrease as the compression pressure increased. Heating of ibuprofen compacts at temperatures below their melting point had a significant effect on the tensile strength of the compacts which was attributed to sintering. Ibuprofen compacts heated at a higher temperature showed a more significant increase in tensile strength than those heated at a lower temperature for the same heating time. At all the sintering temperatures studied, the effect of heating time on compact tensile strength was most pronounced at the lowest packing fraction. As packing fraction increased, the effect of heating time on tensile strength diminished. Microstructural changes in ibuprofen compacts, such as pore rounding and pore shrinkage, were substantiated by the SEM photomicrographs of the surface and cross-section of the sintered compacts. Using mercury intrusion porosimetry, a marked reduction in total pore volume and a shift to a narrower width of pore size distribution were demonstrated for compacts after sintering. For compacts prepared at higher pressures, the reduction in both total pore volume and pore size were found to occur at a faster rate as compared to those formed with a lower pressure. By using the nitrogen adsorption method, the mesopore volume for an ibuprofen compact was shown to increase as a result of sintering. This observation is consistent with the proposed sintering mechanism which would predict an increase in the mesopore volume as a result of the shrinkage of macropores in a compact during sintering.
Degree
Ph.D.
Advisors
Peck, Purdue University.
Subject Area
Pharmaceuticals
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