The aim of this work was to investigate the dissolution rate from both the curved and planar surfaces of cylindrical compacts of benzoic acid, which were placed centrally and non-centrally at the base of the vessel of the paddle dissolution apparatus. The effect of fixing the compacts to a particular position on the variability of dissolution results was also examined. In addition, computational fluid dynamics (CFD) was used to simulate fluid flow around compacts in the different positions in the vessel, and the relationship between the local hydrodynamics in the region of the compacts and the dissolution rate determined. The dissolution rate was found to increase from the centre position to the off-centre positions for each surface examined. There was a corresponding increase in maximum fluid velocities calculated from the CFD fluid flow simulations at a fixed distance from the compact. There was less variability in dissolution from compacts fixed to any of the positions compared with those that were not fixed. Fluid flow around compacts in different positions could be successfully modelled, and hydrodynamic variability examined, using CFD. The effect of asymmetric fluid flow was evident visually from the change in shape of the eroded compacts.

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Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CLCR and serum albumin concentration are important considerations for appropriate dosing.

A low velocity pulsing flow running counter to gravity inhibited the experimental dissolution rate compared to that in a free convection system. From the CFD simulations generated, simulation of both hydrodynamics and species transfer is recommended to characterise the influence of hydrodynamics on dissolution in a low velocity pulsing flow.

19Objectives: To describe the population pharmacokinetics of teicoplanin in adult haematological 20 malignancy patients receiving higher than standard doses and to perform Monte Carlo simulations 21 to determine dosing regimens associated with optimal teicoplanin concentrations. 22Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). Nine blood samples 23 were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 h post last 24 dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates 25 from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were 26 undertaken using Pmetrics®. 27Results: Thirty adult haematological malignancy patients were recruited with a mean (SD) loading 28 dose, age, total body weight and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) that administering five loading doses 12-h, stratified by total body weight and creatinine clearance, 36 increased the probability of achieving target concentrations within 72 h. 37Conclusions: To increase the number of patients achieving optimal teicoplanin concentrations an 38 individualised dosing approach, based on body weight and creatinine clearance, is recommended. 39 40