Krka, d.d., Novo mesto, Šmarješka cesta 6, 8000 Novo mesto, Slovenia; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Int J Pharm. 2015 Nov 10;495(1):336-346. doi: 10.1016/j.ijpharm.2015.08.099. Epub 2015 Sep 1.
The purpose of this study was to compare different solidification techniques (i.e., adsorption technique, spray-drying process, high-shear granulation, fluid-bed granulation) for preparing solid SMEDDS powders by using solid carriers identified as appropriate and to produce a single (tablets) or multiunit (minitablets) solid dosage form based on prepared solid SMEDDS loaded with naproxen in a dissolved (6% w/w) or supersaturated (18% w/w) state. Among the solidification techniques and carriers tested, the powders produced using the spray-drying process and maltodextrin (MD) as a carrier exhibited the best self-microemulsifying properties, comparable with liquid SMEDDS. Furthermore, DoE (Design of Experiments) showed that pressure at the nozzle and pump speed (regulating feed flow rate) applied during spray drying had a major and significant influence on self-microemulsifying properties (mean droplet size and PDI) of the solid SMEDDS prepared. Furthermore, it was shown that compression of solid SMEDDS into (mini) tablets influences its self-microemulsifying properties in a negative direction. This resulted in lowering the dissolution profile of naproxen from tablets and minitablets in comparison with liquid and solid SMEDDS. However, all compressed SMEDDS formulations still had considerable influence on the dissolution profile and solubility enhancement of naproxen.
本研究的目的是比较不同的固化技术(即吸附技术、喷雾干燥工艺、高剪切制粒、流化床制粒),以使用确定为合适的固体载体来制备固体 SMEDDS 粉末,并基于载有萘普生的制备固体 SMEDDS 制备单一(片剂)或多单位(迷你片剂)固体剂型,载药状态为溶解(6%w/w)或过饱和(18%w/w)。在所测试的固化技术和载体中,使用喷雾干燥工艺和麦芽糊精(MD)作为载体制备的粉末表现出最佳的自微乳化性能,与液体 SMEDDS 相当。此外,实验设计(DoE)表明,喷雾干燥过程中喷嘴压力和泵速(调节进料流速)对制备的固体 SMEDDS 的自微乳化性能(平均液滴尺寸和 PDI)有重要影响。此外,研究表明,将固体 SMEDDS 压缩成(迷你)片剂会对其自微乳化性能产生负面影响。这导致与液体和固体 SMEDDS 相比,萘普生从片剂和迷你片剂中的溶解曲线降低。然而,所有压缩的 SMEDDS 制剂仍然对萘普生的溶解曲线和溶解度增强有显著影响。