Drug Dynamics Institute, College of Pharmacy, University of Texas at Austin, Austin, TX, USA.
J Microencapsul. 2010;27(6):521-32. doi: 10.3109/02652048.2010.484105.
Matrix-type pellets with controlled-release properties may be prepared by hot-melt extrusion applying a single-step, continuous process. However, the manufacture of gastric-resistant pellets is challenging due to the high glass transition temperature of most enteric polymers and an unacceptably high, diffusion-controlled drug release from the matrix during the acidic phase. The objective was to investigate the influence of three plasticizers (triethyl citrate, methylparaben and polyethylene glycol 8000) at two levels (10% or 20%) on the properties of hot-melt extruded Eudragit S100 matrix pellets. Extrusion experiments showed that all plasticizers produced similar reductions in polymer melt viscosity. Differential scanning calorimetry and powder X-ray diffraction demonstrated that the solid state plasticizers were present in the amorphous state. The drug release in acidic medium was influenced by the aqueous solubility of the plasticizer. Less than 10% drug was released after 2 h at pH 1.2 when triethyl citrate or methylparaben was used, independent of the plasticizer level. Drug release at pH 7.4 resulted from polymer dissolution and was not influenced by low levels of plasticizer, but increased significantly at the 20% level. Mechanical testing by diametral compression demonstrated the high tensile strength of the hot-melt extruded pellets that decreased when plasticizers were present.
采用一步法、连续工艺通过热熔挤出法可制备具有控释性能的基质型丸剂。然而，由于大多数肠溶聚合物的玻璃化转变温度较高，并且在酸性阶段，药物从基质中以扩散控制方式释放的速度过快，使得胃溶型丸剂的制备颇具挑战性。本研究的目的是考察三种增塑剂（柠檬酸三乙酯、对羟基苯甲酸甲酯和聚乙二醇 8000）在两个水平（10%或 20%）下对 Eudragit S100 热熔挤出基质丸剂性能的影响。挤出实验表明，所有增塑剂均使聚合物熔体黏度产生相似程度的降低。差示扫描量热法和粉末 X 射线衍射表明，固态增塑剂以无定形态存在。在酸性介质中的药物释放受增塑剂水溶解度的影响。当使用柠檬酸三乙酯或对羟基苯甲酸甲酯时，在 pH 1.2 下 2 h 后释放的药物少于 10%，而增塑剂的水平则不影响这一结果。在 pH 7.4 下的药物释放则源于聚合物的溶解，低水平的增塑剂对此没有影响，但在 20%的水平时则显著增加。通过压直径试验进行的力学测试表明，热熔挤出丸剂具有较高的拉伸强度，而添加增塑剂后则会降低。
