Sgrott, O. L. Jr JrTaborda, M. A.Koullapis, P.Bauer, K....
21页
查看更多>>摘要：Airflow and aerosol deposition in the human airways are important aspects for applications such as pulmonary drug delivery and human exposure to aerosol pollutants. Numerical simulations are widely used nowadays to shed light in airflow features and particle deposition patterns inside the airways. For that purpose, the Euler/ Lagrange approach is adopted for predicting flow field and particle deposition through point-particle tracking. Steady-state RANS (Reynolds-averaged Navier-Stokes) computations of flow evolution in an extended lung model applying different turbulence models were conducted and compared to measurements as well as high resolution LES (large-eddy simulations) for several flow rates. In addition, various inlet boundary conditions were considered and their influence on the predicted flow field was analysed. The results showed that the mean velocity field was simulated reasonably well, however, turbulence intensity was completely under-predicted by two-equation turbulence models. Only a Reynolds-stress model (RSM) was able predicting a turbulence level comparable to the measurements and the high resolution LES. Remarkable reductions in wall deposition were observed when wall effects were accounted for in the drag and lift force expressions. Naturally, turbulence is an essential contribution to particle deposition and it is well known that two-equation turbulence models considerably over-predict deposition due to the spurious drift effect. A full correction of this error is only possible in connection with a Reynolds-stress turbulence model whereby the predicted deposition in dependence of particle diameter yielded better agreement to the LES predictions. Specifically, with the RSM larger deposition is predicted for smaller particles and lower deposition fraction for larger particles compared to LES. The local deposition fraction along the lung model was numerically predicted with the same trend as found from the measurements, however the values in the middle region of the lung model were found to be somewhat larger.
查看更多>>摘要：The release of quality, safe, and effective non-sterile drugs needs to exclude the presence of objectionable microorganisms, which include microorganisms potentially involved in product degradation, or considered as poor hygiene indicator during manufacturing, or causing adverse effect on patient's health. In this paper, a method allowing objective and verifiable evaluations has been investigated through the development of a suitable decision tree with a template for data collection. The decision tree has been used to establish which microorganisms were objectionables, using several hypothetical scenarios in which 24 different biological agents, both harmless microorganisms and opportunistic pathogens, were combined with 9 different products, representing each type of administration route for non sterile drugs. The results showed that the use of aforementioned approach makes the microorganisms evaluation easy and verifiable and highlighted that even the microbes initially considered harmless could be objectionable.
查看更多>>摘要：Nanocrystal formulations of the BCS class II agomelatine, were developed by wet media milling. The most suitable stabilizer was identified and effects of process and formulation variables on the nanocrystal size and zeta-potential were evaluated employing a Box-Behnken experimental design. The optimized nanosuspensions were dried and subsequently evaluated for redispersibility and physicochemical properties. Computational simulation of solid state properties was applied to rationalize crystal fracture. It was found that low viscosity hydroxypropylcellulose with sodium dodecyl sulfate is the most suitable stabilizer. Stabilizer concentration exerts a statistically significant effect on particle size, which depends on the mill's rotation speed. The milling process induces a polymorphic transition to form II, which could affect size reduction kinetics. The solidified nanosuspensions' redispersibility is deteriorating progressively with storage time, with only minor differences between drying methods, retaining enhanced dissolution rate. Crystal lattice simulations suggest high mechanical anisotropy of form I crystals, which could be an additional reason for fast particle size reduction prior to the polymorphic transformation. Wet media milling, combined with a suitable drying method, can be an efficient technique for the production of stable nanocrystals of agomelatine. Particle informatics methods can enhance our understanding of the mechanisms responsible for agomelatine's nanocomminution.
NSTL
Elsevier