Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ, USA.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1046-55. doi: 10.1016/j.ejpb.2013.07.015. Epub 2013 Jul 31.
The use of fluid bed granulation for drying of pharmaceutical nanoparticulates on micron-sized granule substrates is a relatively new technique, with limited understanding in the current literature of the effects of process parameters on the physical properties of the dried nanoparticle powders. This work evaluated the effects of spray mode, spray rate and atomizing pressure for spray granulation of drug nanosuspensions through a systematic study. Naproxen and a proprietary Novartis compound were converted into nanosuspensions through wet media milling and dried onto a mannitol based substrate using spray granulation. For naproxen, various physical properties of the granules, as well as the in vitro re-dispersion and dissolution characteristics of the nano-crystals, were measured. It was found that the spray mode had the most drastic effect, where top spray yielded smaller re-dispersed particle sizes and faster release rates of drug from granules than bottom spray. This was attributed to the co-current spraying in bottom spray resulting in denser, homogenous films on the substrate. Similar in vitro results were obtained for the proprietary molecule, Compound A. In vivo studies in beagle dogs with Compound A showed no significant difference between the liquid and the dried forms of the nanosuspension in terms of overall AUC, differences were observed in the tmax which correlated with the rank ordering observed from the in vitro dissolution profiles. These findings make spray granulation amenable to the production of powders with desired processing and handling properties, without compromising the overall exposure of the compound under investigation.
流化床造粒干燥药物纳米颗粒在微米级颗粒载体上的应用是一项相对较新的技术，目前文献中对工艺参数对干燥纳米颗粒粉末物理性质的影响的了解有限。本工作通过系统研究评估了喷雾模式、喷雾速率和雾化压力对药物纳米混悬液喷雾造粒的影响。通过湿磨法将萘普生和诺华公司的一种专有化合物制成纳米混悬剂，然后通过喷雾造粒将其干燥在甘露醇载体上。对于萘普生，测量了颗粒的各种物理性质以及纳米晶体的体外再分散和溶解特性。结果发现，喷雾模式的影响最大，顶喷比底喷产生更小的再分散颗粒尺寸和更快的药物释放速率。这归因于底喷中的并流喷雾导致载体上形成更致密、均匀的薄膜。对于专有分子化合物 A，也获得了类似的体外结果。体内研究表明，在 Beagle 犬中，与纳米混悬液的液态形式相比，化合物 A 的干燥形式在 AUC 方面没有显著差异，仅在 tmax 方面存在差异，这与体外溶解曲线的排序结果相关。这些发现表明喷雾造粒可生产具有所需加工和处理性能的粉末，而不会影响研究化合物的整体暴露。
