Influence of different sources on the processing and biopharmaceutical properties of high-dose ibuprofen formulations.

It is known that depending on the manufacturing and synthetic processes, drugs may exist as different forms. As a result, physicochemical properties, compression characteristics, intrinsic dissolution and bioavailability may vary substantially. The purpose of this study was to investigate the effect of different sources of ibuprofen on the processing of tablets and on their properties. Another emphasis of this work was to rationalize one or several key characteristics of the raw material as directly related to wet granulation parameters and to the behavior of final tablets. Commercially available ibuprofen was obtained from different manufacturers and a preformulation program, including X-ray crystallography, differential scanning calorimetry, scanning electron microscopy, determination of particle size distribution and flowability, was performed to characterize the raw material. Granules were prepared with a planetary mixer and liquid requirements for the end point were obtained by monitoring power consumption. Tablets were manufactured on Stokes rotary and single punch instrumented presses. Data acquisition interfaces produced compression data for each formulation. Granules and final tablets were analyzed for hardness, dissolution profiles and content uniformity. Statistical evaluations using analysis of variance and multiple comparison procedures were performed on the results to determine the significance of the variability between independent parameters. The ibuprofen tested was found to be a unique polymorphic form with some differences in the external crystallinity. The particle size characteristics of the material also allowed a differentiation between sources and although there was no differences in dissolution patterns or content uniformity, particle size was found to account for 50% of the variability in tablet hardness. Two sources of ibuprofen with lower mean particle size showed significant variations in end point liquid requirements resulting in variable tablet crushing strength.