Podczeck Fridrun, Maghetti Ana, Newton J Michael
Department of Mechanical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK.
Eur J Pharm Sci. 2009 Jun 28;37(3-4):334-40. doi: 10.1016/j.ejps.2009.03.003. Epub 2009 Mar 20.
The influence of adding two concentrations (5 and 25%) of non-ionic surfactants, one hydrophilic and the other hydrophobic, plus mixtures of equal parts of the two, on the rheological properties of a mixture of equal parts of microcrystalline cellulose and ibuprofen with water has been assessed by capillary rheometry. The mixtures were also used to form pellets by extrusion/spheronization and their in vitro dissolution in simulated intestinal fluid was measured. As with previous rheological studies of these types of pastes, the flow was non-Newtonian (shear thinning). Other rheological parameters were determined in terms of die entry angles, extensional flow and elastic parameters of recoverable shear and compliance. By comparisons with previous studies with the model drug, it was found that it was these latter parameters that were indicative of the ability of the formulations to produce satisfactory pellets. The experiments also identified that the level of surfactant as opposed to the type of surfactant determined the rheological properties of the wet mass. All the formulations were able to produce round pellets with a narrow size distribution, whereby their median size increased with the concentration of the surfactant. The 25% level of each of the surfactant formulations provided a rapid release of the drug (100% within 30min), but the 5% level and the mixed surfactant formulations provided lower drug release profiles.
通过毛细管流变仪评估了添加两种浓度（5%和25%）的非离子表面活性剂（一种亲水，另一种疏水）以及两者等份混合物，对微晶纤维素、布洛芬与水等份混合物流变学性质的影响。这些混合物还用于通过挤出/滚圆法制备微丸，并测定其在模拟肠液中的体外溶出度。与以往对这类糊剂的流变学研究一样，其流动为非牛顿型（剪切变稀）。根据口模入口角、拉伸流动以及可恢复剪切和柔量的弹性参数确定了其他流变学参数。通过与之前模型药物的研究进行比较，发现正是这些后述参数表明了制剂生产出令人满意微丸的能力。实验还确定，表面活性剂的用量而非类型决定了湿物料的流变学性质。所有制剂都能制备出尺寸分布窄的圆形微丸，其中位数尺寸随表面活性剂浓度增加而增大。每种表面活性剂制剂的25%用量使药物快速释放（30分钟内达100%），但5%用量以及混合表面活性剂制剂的药物释放曲线较低。
