Institute of Pharmaceutical Sciences/Pharmaceutical Technology, Karl-Franzens University of Graz, Graz, Austria.
Eur J Pharm Biopharm. 2010 May;75(1):56-62. doi: 10.1016/j.ejpb.2010.01.005. Epub 2010 Jan 18.
The aim of the study was the development of lipophilic pellets containing calcium stearate and ibuprofen as model drug. The pellets were produced by a standard wet extrusion and spheronisation technology. As a main target, the pellets should exhibit sufficient mechanical stability, should not disintegrate in an aqueous vehicle and should show a retarded release kinetic. Furthermore, the drug release should be adjusted only by the ratio between drug and excipient without any additional coating procedure.
Different lipids (Precirol(R), Compritol(R), glyceryl monostearate, magnesium stearate and vegetable calcium stearate) were used as lipophilic pelletisation excipients in extrusion/spheronisation using ethanol/water as granulation liquid. The lipids were combined with ibuprofen as a model drug with pH-dependent solubility in several concentrations (15%, 20% and 25% drug content).
Calcium stearate (CS) was found to be a suitable carrier substance for the preparation of spherical pellets (AR1.2). As pellet properties, the mean particle random diameter, surface area, porosity, tensile strength and dissolution profile were determined. By variation of the die plate (1mm, 0.8mm and 0.5mm) and variation of the ethanol/water composition (96% and 50%) of the granulation liquid, pellets in the size range from 800 to 1250microm with a sufficient drug loading capacity up to 20%, a zero-order drug release and high mechanical stability could be produced.
The results demonstrated that calcium stearate can be used as pelletisation excipient for slow release formulations by a wet extrusion/spheronisation technique. With this technology, a continuous production of slow release multiple unit preparations will be possible without further coating steps.
本研究的目的是开发含有硬脂酸钙和布洛芬的亲脂性微丸，作为模型药物。微丸采用标准的湿挤压和滚圆技术制备。主要目标是使微丸具有足够的机械稳定性，在水性介质中不崩解，并表现出延迟释放动力学。此外，药物释放可以仅通过药物与赋形剂的比例来调节，而无需任何额外的包衣程序。
使用不同的脂质（Precirol（R）、Compritol（R）、单硬脂酸甘油酯、硬脂酸镁和植物硬脂酸钙）作为亲脂性挤出/滚圆的赋形剂，以乙醇/水为造粒液。将这些脂质与布洛芬（一种具有 pH 依赖性溶解度的模型药物）以不同浓度（15%、20%和 25%的药物含量）结合。
硬脂酸钙（CS）被发现是制备球形微丸（AR1.2）的合适载体物质。作为微丸的性质，测定了平均颗粒随机直径、表面积、孔隙率、拉伸强度和溶解曲线。通过改变模具板（1mm、0.8mm 和 0.5mm）和造粒液中乙醇/水的组成（96%和 50%），可以制备出粒径范围为 800 至 1250μm、药物载药量高达 20%、零级药物释放和高机械稳定性的微丸。
结果表明，硬脂酸钙可用作湿挤压/滚圆技术的缓释制剂的赋形剂。通过这项技术，可以实现连续生产缓释多单位制剂，而无需进一步的包衣步骤。
