Development of cordycepin formulations for preclinical and clinical studies

There is extensive literature on in vivo studies with cordycepin but these studies were generally conducted without validation of the various formulations, especially in terms of the solubility of cordycepin in the dosing vehicles used. Cordycepin is a promising drug candidate in multiple therapeutic areas and there is a growing interest in studies aimed at assessing the pharmacological activity of this compound in relevant animal disease models. It is likely that many reported in vivo studies used formulations in which cordycepin was incompletely soluble. This can potentially confound the interpretation of pharmacokinetics and efficacy results. Furthermore, the presence of particles in intravenously administered suspension can cause adverse effects and should be avoided. Here we present the results from our development of simple and readily applicable formulations of cordycepin based on quantitative solubility assessment. Homogeneous solutions of cordycepin were prepared in phosphate-buffered saline (PBS) at different pH levels, suitable as formulations for both intravenously and oral administration. For the purpose of high-dose oral administration we also developed propylene glycol (PPG)-based vehicles in which cordycepin is completely soluble. The stability of the newly developed formulations was also assessed, as well the feasibility of their sterilisation by filtration. Additionally, an HPLC-UV method for the determination of cordycepin in the formulations, which may also be useful for other purposes, was developed and validated. Our study could provide useful information for improvement of future preclinical and clinical studies involving cordycepin

Mitigation of cutting-induced artificial stresses in contour method analysis of irregular components

The contour method is a destructive technique to reconstruct residual stresses that are released when cut with wire electro-discharge machining. This cutting process can potentially introduce artifacts when cutting through components with non-rectangular cross sections. This is most apparent when the instantaneous cross section of the workpiece changes with respect to the cutting orientation. Typically, sacrificial material is employed to regularize the cutting cross section to mitigate artifacts. A further correction method has been realized employing a reference sample in a near stress-free state intended to correct for cutting artifacts without the use of sacrificial material. This new approach is illustrated with residual stress manifesting in two aluminum alloy 7050 friction stir welded T-sections. Measurements made employing neutron diffraction, contour method with sacrificial material and with the new approach are compared and contrasted. While the sacrificial material approach remains the best approach for dealing with the subject component and cross section, the use of a reference sample is shown to reduce errors in the resolved residual stress. Neutron diffraction results have been employed, showing that errors can be reduced as compared to an uncorrected result in some regions, but further errors can be introduced if the reference cut has not been well controlled. This is particularly important for components which may not be able to have sacrificial material applied