Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability
Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability
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DOI：
10.1016/j.ces.2006.08.074
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发表时间：
2007
影响因子：
4.7
通讯作者：
G. Walker;S. Bell;G. Andrews;David S. Jones
中科院分区：
文献类型：
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作者：
G. Walker;S. Bell;G. Andrews;David S. Jones
本研究探讨了使用共熔流化床造粒对模型药物粉末的团聚，即乳糖一水合物，PEG 10000，聚乙烯基pyroli酮和布洛芬作为模型药物。发现共熔体系内的造粒遵循成核-稳定生长-涂层制度剖面。使用高分子量PEG粘结剂，发现粘结剂粘度对造粒机理和造粒程度有显著影响。采用一种新型的高温实验方法对热流化床内颗粒的压缩特性进行了关联。结果表明，热加工条件下材料的断裂应力和断裂模量比常温条件下的测量值低几个数量级。在理论模型的基础上考虑了造粒机内的粒子速度范围。在初始成核期之后，Stokes变形数分析表明，只有在流化床的高剪切区域内的速度才足以促进显著的颗粒变形，从而促进聚并。数据还表明，较大的颗粒脱流防止团聚通过聚结。此外，实验数据表明，黏性粘结剂熔液在造粒过程后期的耗散是最重要的因素。从药学的角度来看，在共融过程中加入模型药物布洛芬和PVP是非常重要的。通过对配方的DSC分析发现，与布洛芬在FHMG体系中熔化相关的熔合热降低可能是由于PVP与布洛芬通过分子间氢键相互作用所致。这种相互作用降低了布洛芬的结晶度，促进了固体基质内的溶解和生物利用度。
This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleation—steady growth—coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.