Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3-dicyclohexylurea in rats: Preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery

1,3-Dicyclohexylurea (DCU), a potent soluble epoxide hydrolase (sEH) inhibitor has been reported to lower systemic blood pressure in spontaneously hypertensive rats. One limitation of continual administration of DCU for in vivo studies is the compound's poor oral bioavailability. This phenomenon is mainly attributed to its poor dissolution rate and low aqueous solubility. Previously, wet-milled DCU nanosuspension has been reported to enhance the bioavailability of DCU. However, the prosperities and limitations of wet-milled nanosuspension have not been fully evaluated. Furthermore, the oral pharmacokinetics of DCU in rodent are such that the use of DCU to understand PK/PD relationships of sEH inhibitors in preclinical efficacy model is less than ideal. In this study, the limitation of orally delivered DCU nanosuspension was assessed by a surface area sensitive absorption model and pharmacokinetic modeling. It was found that dosing DCU nanosuspension did not provide the desired plasma profile needed for PK/PD investigation. Based on the model and in vivo data, a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK/PD studies

A review of CFD modelling and performance metrics for osmotic membrane processes

Simulation via Computational Fluid Dynamics (CFD) offers a convenient way for visualising hydrodynamics and mass transport in spacer-filled membrane channels, facilitating further developments in spiral wound membrane (SWM) modules for desalination processes. This paper provides a review on the use of CFD modelling for the development of novel spacers used in the SWM modules for three types of osmotic membrane processes: reverse osmosis (RO), forward osmosis (FO) and pressure retarded osmosis (PRO). Currently, the modelling of mass transfer and fouling for complex spacer geometries is still limited. Compared with RO, CFD modelling for PRO is very rare owing to the relative infancy of this osmotically driven membrane process. Despite the rising popularity of multi-scale modelling of osmotic membrane processes, CFD can only be used for predicting process performance in the absence of fouling. This paper also reviews the most common metrics used for evaluating membrane module performance at the small and large scales

Planning of progressive group-censoring life tests with cost considerations

This paper considers a life test under progressive type I group censoring with a Weibull failure time distribution. The maximum likelihood method is used to derive the estimators of the parameters of the failure time distribution. In practice, several variables, such as the number of test units, the number of inspections, and the length of inspection interval are related to the precision of estimation and the cost of experiment. An inappropriate setting of these decision variables not only wastes the resources of the experiment but also reduces the precision of estimation. One problem arising from designing a life test is the restricted budget of experiment. Therefore, under the constraint that the total cost of experiment does not exceed a pre-determined budget, this paper provides an algorithm to solve the optimal decision variables by considering three different criteria. An example is discussed to illustrate the proposed method. The sensitivity analysis is also studied.A-optimality, D-optimality, E-optimality, grouped data, maximum likelihood method, progressive censoring, Weibull distribution,