Eulerian ISPH Method for Simulating Internal Flows

In this article the possibility to use Eulerian approach in the conventional ISPH method in simulation of internal fluid flows is studied. The use of Eulerian approach makes it possible to use non-uniform particle distributions to increase the resolution in the sensitive parts of the domain, different boundary conditions can be employed more freely and particle penetration in the solid walls and tensile instability no longer require elaborate procedures. The governing equations are solved in an Eulerian framework containing both the temporal and local derivatives which make the momentum equations non-linear. Some special treatment and smaller time steps are required to remedy this non-linearity of the problem. In this study, projection method is used to enforce incompressibility with the evaluation of an intermediate velocity and then this velocity is projected on the divergence-free space. This method is applied to the internal fluid flows in a shear-driven cavity, Couette flow, a flow inside a duct with variable area and flow around a circular cylinder within a constant area duct. The results are compared with the results of Lagrangian ISPH and WCSPH methods as well as finite volume and Lattice Boltzmann grid based schemes. The results of the studied scheme have the same accuracy for velocity field and have better accuracy in pressure distribution than ISPH and WCSPH methods. Non-uniform particle distributions are also studied to check the applicability of this method and Good agreement is also observed between uniform and non-uniform particle distributions

On the Physical Stability of Leucine-Containing Spray-Dried Powders for Respiratory Drug Delivery

Carrier-free spray-dried dispersions for pulmonary delivery, for which the demand is growing, frequently require the incorporation of dispersibility-enhancing excipients into the formulations to improve the efficacy of the dosage form. One of the most promising of such excipients, L-leucine, is expected to be approved for inhalation soon and has been studied exhaustively. However, during stability, small fibers protruding from the particles of leucine-containing powders have occasionally been observed. To clarify the origin of these fibers and assess their potential influence on the performance of the powders, three different classes of spray-dried leucine-containing formulation systems were studied over an 8-month accelerated stability program. These systems consisted of a large molecule biologic (bevacizumab) in conjunction with a glass former (trehalose), an amorphous small-molecular mass active (moxidectin), and a crystallizing active (mannitol). It was determined that the appearance of the fibers was due to the presence of small quantities of leucine in higher energy states, either because these were amorphous or present as a less stable crystalline polymorph. It was further shown that the growth of these leucine fibers caused no significant physicochemical instability in the powders. Nor, more importantly, did it decrease their aerosol performance in a dry powder inhaler or reduce the concentration of their active pharmaceutical ingredients