Reitz Claudia, Kleinebudde Peter
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany.
Eur J Pharm Biopharm. 2007 Sep;67(2):440-8. doi: 10.1016/j.ejpb.2007.03.008. Epub 2007 Mar 16.
The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5) and glyceryl trimyristate (Dynasan 114), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 degrees C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 degrees C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.
本研究考察了固体脂质挤出工艺作为缓释剂型制备方法的适用性。将两种具有相似熔点范围但组成不同的脂质，即棕榈硬脂酸甘油酯（Precirol ATO 5）和三肉豆蔻酸甘油酯（Dynasan 114），以及每种脂质与50%或75%茶碱的混合物在低于其熔点的温度下进行挤出。使用差示扫描量热法、扫描电子显微镜、孔隙率测量和体外药物溶出研究对挤出物进行分析。结果表明，可以通过软化而非完全熔化来加工脂质，且不会随后形成低熔点的亚稳多晶型物。基于棕榈硬脂酸甘油酯/茶碱（50:50）和三肉豆蔻酸甘油酯/茶碱（50:50）配方的挤出物显示出缓释特性。对于基于三肉豆蔻酸甘油酯和茶碱（50:50）混合物的挤出物，显示出挤出条件对基质结构有影响。三肉豆蔻酸甘油酯在熔化后倾向于在多孔结构中固化。超过50.5℃的物料温度会导致药物释放更快的多孔挤出物基质。在49.5℃的物料温度下可以生产新型的无孔缓释基质。基于三肉豆蔻酸甘油酯/茶碱（50:50）的挤出物的熔化焓仅有轻微变化且药物释放曲线稳定。
