• Mechanical characterization of ibuprofen, naproxen, and their spherically crystallized products

      Anderson, Stephen R.; Augsburger, Larry L. (1997)
      The objectives of this study were to establish a rational basis for choosing parameters for conducting the tensile strength and indentation hardness test on pharmaceutical compacts, to describe the changes in tableting indices based on the different parameters, to develop a method to spherically crystallize ibuprofen, and to compare the mechanical and micromeritic properties of spherically crystallized ibuprofen and naproxen to the starting materials. This work described the importance of establishing the appropriate test parameters for tensile strength and indentation hardness tests so that reliable and predictive tableting indices could be determined. The fracture strength for diametral compression of ibuprofen compacts was determined for two modes of stress application, constant stress rate and constant strain rate. The tensile strength for diametral compression of ibuprofen and naproxen compacts was determined using a constant strain rate (0.05 to 16 mm/min). The static indentation hardness (Meyer hardness) of ibuprofen and naproxen compacts was determined at varying solid fractions and indentor depth of penetration. Results from these studies were used to establish an appropriate rate of stress application during diametral compression and an appropriate depth of penetration for indentation hardness testing in order to calculate tableting indices. The tableting indices calculated from the aforementioned properties were: the brittle fracture index (BFI), the best case bonding index (BIb), the worst case bonding index (BIw), the brittle/viscoelastic bonding index (bBIv), and the viscoelastic index (VI). In addition, changes in compactibility between the starting materials and their spherically crystallized products were assessed through the analysis of Athy-Heckel profiles. A comparison of micromeritic properties included particle size, porosity, surface area, bulk density, tap density, true density, and flowability as measured by the Carr Index. The spherically crystallized products of ibuprofen and naproxen were shown to be free flowing, less compressible, and more compactible than the starting materials. The spherically crystallized ibuprofen product was optimized for improved tensile strength, bonding index, and minimal particle size using response surface experimental design methodology. Key process factors in the quasi-emulsion solvent diffusion method employed to spherically crystallize ibuprofen were: the amount of additive, hydroxypropylmethyl cellulose, added to the nonsolvent, the agitation rate during the crystallization process, and the amount of agglomerating solvent. Naproxen was spherically crystallized using a solvent change method adopted from the open literature. Thermal analysis and x-ray powder diffraction analysis showed that both ibuprofen and naproxen spherically crystallized products were the same highly crystalline form as the starting materials. The relative contribution of the different micromeritic properties to the changes in the mechanical properties was exemplified by the change in BFI. (Abstract shortened by UMI.)