Modeling the uniaxial compaction of pharmaceutical powders using the mechanical properties of single crystals. II: Brittle materials.

A model is presented which uses the hardness and elastic moduli of brittle crystals, determined using the Vickers microindentation test, to predict the uniaxial compaction behavior of compacts. A general approach first developed in the materials science field to predict the densification of particulate matter under hydrostatic loading was followed. Modifications to account for the effects of particle geometry and the closed-die loading conditions were considered. The model predicted the densification behavior of sucrose and adipic acid. It did not predict the densification of acetaminophen as well; however, the discrepancy between the experimental and predicted values may arise either from error associated with the evaluation of the elastic modulus using the microindentation test or from error in calculating the relative density of compacts which were observed to have partially laminated. The effects of error both in the hardness value and in the ratio of punch to die-wall stress on the predictive capability of the model were also discussed briefly.

Modeling the uniaxial compaction of pharmaceutical powders using the mechanical properties of single crystals. I: Ductile materials.

A model is presented which uses the Vickers microindentation hardness of ductile crystals such as sodium chloride to predict the uniaxial compaction behavior of compacts. A general approach first developed in the materials science field to predict the densification of particulate matter under hydrostatic loading was followed. However, modifications to account for the effects of particle geometry and the closed-die loading conditions were considered. Using the standard microindentation hardness value of sodium chloride, the model predicted the densification behavior of this material at a punch displacement rate of 1 mm/min. Densification at higher compaction rates was predicted by considering the effect of deformation kinetics on the hardness. Secondary factors which affect compaction, such as particle size effects and die-wall friction, are also briefly discussed.

Evaluating the deformation kinetics of sucrose crystals using microindentation techniques.

The deformation kinetics of sucrose crystals were evaluated using the Vickers microindentation technique. A (100) face of a crystal of sucrose was indented for varying lengths of time at temperatures ranging from 23 to 103 degrees C, and the deformation kinetics analysis proposed by Verrall et al. (1) was employed to calculate the strain rate and stress from the indentation time and the size of the indentation. Two kinetic parameters, the activation volume and the activation energy, were calculated from the experimental data and compared to those of other materials on normalized scales. The results suggest that the deformation kinetics of sucrose resemble those of ice, the crystal lattice of which is highly hydrogen-bonded, similar to that of sucrose.

Analytical and structural electron microscopy of chromium carcinogenesis in vitro.

Syrian hamster embryo cells have been grown in culture on thin (10-50 nm), evaporated substrates of chromium, and examined by analytical transmission electron microscopy. After 10 d exposure, significant metal uptake was observed and numerous cell colonies showed the physical characteristics of carcinogenic transformation. The majority of the ingested chromium appeared to be associated with nucleic acid complexes. As a control, cells grown on titanium showed no signs of metal uptake and had morphologies very similar to cells grown on conventional carbon substrates.

Evaluating the fracture toughness of sucrose crystals using microindentation techniques.

The brittleness of pharmaceutical crystals influences their ability to form compacts of acceptable quality. While many macroscopic methods are available to elucidate the fracture behavior of materials, the porosity, inhomogeneity, and anisotropy of pharmaceutical compacts render it difficult to interpret the results of these tests. Microindentation techniques may be used to evaluate both the flow and the fracture characteristics of small crystals, so that it is not necessary to test compacts. The flow and fracture behavior of sucrose, the model substance used in this study, were anisotropic. The fracture surface energy, derived from the average fracture toughness value, is of the same order of magnitude as the surface free energy, indicating that sucrose fractures in a brittle manner.

The fatigue strength of porous-coated Ti-6%Al-4%V implant alloy.

The fatigue behaviour of Ti-6Al-4V (extra low interstital) alloy coated with Ti-6Al-4V powder was investigated using rotating bending fatigue testing. It was found that the high cycle fatigue strength of porous coated specimens exhibited a substantial decrease compared to uncoated specimens of the same microstructure. Chemical analysis of the sintered surface revealed significant increases of interstitials compared to the bulk analysis, but it is concluded that this would not adversely affect the fatigue strength. Scanning electron microscopy revealed crack initiation close to particle/substrate contact interfaces and it is concluded that stress intensification due to these interface regions are major sources of weakness with respect to fatigue strength. Finally it was found that subjecting a polished Ti-6Al-4V specimen to the heat treatment required for sintering resulted in delineation of prior beta grain boundaries and it is suggested that this also contributes to the inferior fatigue strength of porous coated Ti-6Al-4V.

Effect of pore size on the peel strength of attachment of fibrous tissue to porous-surfaced implants.

Twenty-four rectangular metal plates were fabricated with surface regions in three different pore size ranges (5-20 microns, 20-50 microns, 50-200 microns). The plates were implanted into the dorsal subcutaneous tissue of 12 adult mongrel dogs for periods of 4, 8, 12, and 16 weeks. After animal sacrifice, the fibrous tissue which adhered to the porous-surfaced regions of each plate was mechanically peeled off to give an indication of the strength of tissue attachment. The tissue was examined by both transmitted light and scanning electron microscopy. At each time period, the tissue that contacted the porous regions was found to be collagenized fibroconnective tissue. The mechanical tests indicated an increasing strength of tissue attachment with increasing implantation time and pore size range. The largest pore size range of approximately 50-200 microns produced a mean peel strength of attachment of 27.5 g/mm at the 16-week period.

Biologic fixation and bone modeling with an unconstrained canine total knee prosthesis.

To study the effects of dynamic loading on biologic fixation, an unconstrained type of prosthesis was designed for total replacement of the knee joint of dogs. The femoral component was fabricated from cast cobalt-based surgical alloy. The tibial component was fabricated from surgical grade, ultra-high molecular weight, high density polyethylene. Both components were designed for initial stabilization at surgery by mechanical interlock with bone. In addition, the bone-interfacing surface of the metal component was made porous and the stem of the polymer component was grooved to permit the subsequent ingrowth of tissue. Knee arthroplasty was performed on a total of six beagles. The prostheses were monitored for periods of 20 months and demonstrated an overall excellent stability and functionality. Each tibial component became stabilized by the formation of a thin, surrounding shell of osseous tissue. Interposed between this bone and the implant was usually a thin layer of fibrous tissue, suggesting micromovement during loading. Each femoral component became solidly fixed by bone growth into the porous surface. The altered stress state in the region of the implant eventually resulted in reactive bone modeling, with both bone formation and resorption occurring along the length of the implant.

Phase identification and incipient melting in a cast Co--Cr surgical implant alloy.

Phase relationships in cast Co--Cr surgical implant alloys, heat treated at temperatures from 1180 to 1300 degrees C, are reported. Interdendritic material was identified by selected area diffraction as a quaternary near eutectic mixture between sigma phase, M23C6, M7C3, and fcc Co. Incipient melting and subsequent resolidification of this near-eutectic mixture accounts for observations of behavior at temperatures above 1235 degrees C. At temperatures just below its melting point the interdendritic material initially breaks down to M23C6, which subsequently dissolves in the Co matrix.

A study of bone remodeling using metal-polymer laminates.

Bone remodeling due to stress-shielding has been studied using a model system consisting of metal-polymer laminated fixation plates securely fixed to canine femurs. The plate stiffness was controlled by varying the ratio of metal facing to polymer core thickness in the laminate design while secure fixation to bone was achieved by providing a porous bone interfacing surface for the ingrowth of bone from the periosteal surface. Observations of laterally and medially placed plates indicated resorption in the area of the periosteal and endosteal bone surfaces respectively, for the higher stiffness composite plates used. The results indicate that plate stiffness greater than approximately 70 GPa (axial) and 6 N m2 (flexural) will result in extensive bone remodeling in the canine femur after a six month implantation period.

Osteogenic phenomena across endosteal bone-implant spaces with porous surfaced intramedullary implants.

Porous surfaced femoral components of hip prostheses stabilized by tissue ingrowth are often situated a certain distance away from the endosteal cortex in the diaphysis. The purpose of this study was to examine the significance of this space between an implant and the cortex on bone growth into the porous surface of the implant. Intramedullary rods of different diameters with porous surface regions made of powder metal were inserted into the femurs of adult beagles. The rods had outside diameters of 2.5, 3.2, 4.5, and 5.5 millimeters; this variation produced endosteal bone-implant surface spaces ranging from 0 to 4 millimeters. The animals were sacrificed at 4, 8, 12, and 16 weeks. Histological sections revealed that by 12 weeks the implants became generally surrounded by a thin shell of spongy bone which was joined to the endosteal cortex by bony trabeculae. This feature was most prominent for implants which were approximately 2 millimeters or less from the endosteum. Denser, more haversian-like bone developed up to and within those areas of implants which were in contact with the cortex. The development of this intramedullary type of bone could significantly contribute to the fixation strength of clinical porous surfaced prostheses whose stems do not completely fill the medulla.

The optimum pore size for the fixation of porous-surfaced metal implants by the ingrowth of bone.

For a study on the effects of pore size variation on the rate of bone growth into porous-surfaced metallic implants and on the strength of fixation resulting from this ingrowth, 4 distinct pore size ranges were prepared on cobalt-base alloy implants with cobalt-base alloy powder particles of different dimensions. The porous implants were placed into canine femurs for periods of 4, 8, and 12 weeks. Mechanical tests were performed to measure the shear strength of fixation of the implants to cortical bone. For implants with powder-made porous surfaces, a pore size range of approximately 50 to 400 microns provided the optimum or maximum fixation strength (17 MPa) in the shortest time period (8 weeks).

The effect of porous surface configuration on the tensile strength of fixation of implants by bone ingrowth.

In an attempt to gain information that could be directly applied to the design of clinical porous-surfaced prostheses intended for biological attachment by bone ingrowth, the tensile strength of the bone-implant interface was expressed as a function of 2 fundamentally different porous-surface configurations. Using powder metallurgy techniques, standard 3-hole fracture fixation plates were prepared with both a single and a multiple layer of spherically shaped metal powder particles on the bone-contacting surface to produce implants with different porous surfaces. These plates were implanted onto the lateral aspect of canine femurs for periods of 4, 6, 8, 12, 18, and 24 weeks. Mechanical tests were performed to measure the tensile strength of fixation of the implants by the ingrowth of bone. The results of the mechanical tests indicated that implants with the multiple particle layer surfce configuration develop a greater tensile strength of fixation than do implants with the single particle layer surface configuration. In addition, this fixation strength develops more quickly if the cortical bone is petaled prior to implantation. These findings should be considered when designing porous-surfaced implants intended for fixation by bone ingrowth.