AFM study of hydrophilicity on acetaminophen crystals.

Pharmaceutical powder processing is notoriously subject to unpredictable jamming, sticking and charging disturbances. To unveil the material science underlying these effects, we use atomic force microscopy (AFM) on a common pharmaceutical, acetaminophen (APAP). Specifically, we study surface adhesion and morphology as a function of relative humidity (RH) for monoclinic acetaminophen, using both plain AFM tips and tips functionalized to be hydrophobic or hydrophilic. Results indicate that the (001) crystal face exhibits significantly higher adhesion (surface potential) than the other crystal faces. For all the faces clear peaks in adhesion occur at 50-60% RH when they are examined using hydrophilic tips. The surface morphology of some facets showed a strong dependence on RH while others showed little or no significant change. In particular, the morphology of the (1-10) faces developed large terraces at high humidity, possibly due to deliquescence followed by recrystallization. These results confirm the hypothesis that different crystal facets exhibit distinct surface potentials and morphology that change with environmental exposure. The work suggests that future studies of powder behaviors would benefit from a more detailed modeling of crystal surface contact mechanics.

High frequency ultrasound prediction of mechanical properties of cortical bone with varying amount of mineral content.

In this study, we evaluate if high frequency ultrasound impedance measurements can predict the mechanical properties of bones where the amount of bone mineral is varied. The motivation stems from the potential utility of ultrasound as a noninvasive technique to evaluate and monitor the mechanical properties of bone during treatment of diseased states where the ratio of mineral content to organic matrix content could change (e.g., metabolic bone diseases, osteoarthritis, osteogenesis imperfecta, fracture healing). Eleven cortical bovine femur samples, which were taken along the long axis of femur, were used in each group. Bone samples with reduced mineral content (estimated to be 21% and 35% less than the control) were obtained by immersing samples into fluoride ion solution for 3 and 12 d. Control and fluoride treated samples were first tested mechanically in tension. Acoustic impedances of the mechanically tested samples were obtained by using scanning acoustic microscopy (SAM). Results from mechanical tests indicate that the tensile elastic modulus of the samples was highly correlated to the yield strength (r(2) = 0.94, p < 0.01) and to the ultimate strength (r(2) = 0.75, p < 0.01). SAM results indicate that the acoustic impedances were significantly correlated to the elastic modulus (r(2) = 0.85, p < 0.01), yield strength (r(2) = 0.86, p < 0.01) and ultimate strength (r(2) = 0.70, p < 0.01). These results show that ultrasonic techniques could potentially be used to predict the in vivo ultimate strength of bone tissue caused by changes in mineral content.

Osteopontin deficiency and aging on nanomechanics of mouse bone.

Osteoporosis is a bone disease characterized by low bone mass and deterioration of the tissue leading to increased fragility. Osteopontin (OPN), a noncollageneous bone matrix protein, has been shown to play an important role in osteoporosis, bone resorption, and mineralization. However, OPN's role in bone mechanical properties on the submicron scale has not been studied in any detail. In this study, nanoindentation techniques were utilized to investigate how OPN and aging affect bone mechanical properties. Hardness and elastic modulus were calculated and compared between the OPN-deficient mice (OPN(-/-)) and their age and sex-matched wild-type (OPN(+/+)) controls. The results show that the mechanical properties of the young OPN(-/-) bones (age < 12 weeks) are significantly lower than that of the youngest OPN(+/+) bones. This finding was confirmed by additional microindentation testing. Biochemical analysis using micro-Raman spectroscopy indicated more mineral content in young OPN(+/+) bones. Older (age > 12 weeks) bones did not show any significant differences in mechanical properties with genotype. In addition, OPN(+/+) bones show a decrease in mechanical properties between young and older age groups. By contrast, OPN(-/-) bones showed no significant change in mechanical properties with aging.