Wu Chuanbin, McGinity James W
College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
Eur J Pharm Biopharm. 2003 Jul;56(1):95-100. doi: 10.1016/s0939-6411(03)00035-3.
The purpose of this study was to investigate the properties of methylparaben as a solid-state plasticizer for Eudragit RS PO during a hot-melt extrusion process. Extruded matrices containing different levels of methylparaben and Eudragit RS PO, were prepared by feeding the powder blend through a hot melt extruder. The melt viscosity of the polymer blends was assessed by torque rheometry using a Brabender Plasticorder. The physicochemical properties of the extruded methylparaben-containing polymer matrix were characterized by differential scanning calorimetry and X-ray diffraction. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to study the possible interaction between methylparaben and Eudragit RS PO polymer. The results demonstrated that the glass transition temperature of the Eudragit RS PO decreased with increasing levels of methylparaben in the extrudate, due to an increase in the chain mobility of Eudragit RS PO. The crystallinity of methylparaben was absent following hot-melt processing. At increasing levels of methylparaben in the extrudates, a decrease in the melt viscosity was seen due to a plasticization of the polymer. Rheological properties of the extrudates containing methylparaben were compared with the extrudates containing conventional plasticizers. It was found that methylparaben was as effective as triethyl citrate (TEC) in reducing torque during the extrusion process. Solid state NMR spectra indicated a change in the chemical shift of Eudragit RS PO plasticized with methylparaben, which could be ascribed to an interaction between the hydroxyl group of the methylparaben and the ester group of the Eudragit RS PO polymer. The results of this study demonstrated that methylparaben could be used as a solid-state plasticizer for the Eudragit RS PO polymer when a hot melt extrusion technique was employed in the preparation of sustained release tablets.
本研究的目的是考察对羟基苯甲酸甲酯在热熔挤出过程中作为Eudragit RS PO的固态增塑剂的性能。通过将粉末混合物送入热熔挤出机，制备了含有不同水平对羟基苯甲酸甲酯和Eudragit RS PO的挤出基质。使用Brabender塑度仪通过转矩流变学评估聚合物共混物的熔体粘度。通过差示扫描量热法和X射线衍射对挤出的含对羟基苯甲酸甲酯聚合物基质的物理化学性质进行表征。使用固态核磁共振光谱（NMR）研究对羟基苯甲酸甲酯与Eudragit RS PO聚合物之间可能的相互作用。结果表明，由于Eudragit RS PO链流动性增加，挤出物中对羟基苯甲酸甲酯水平的增加导致Eudragit RS PO的玻璃化转变温度降低。热熔加工后对羟基苯甲酸甲酯无结晶性。随着挤出物中对羟基苯甲酸甲酯水平的增加，由于聚合物的增塑作用，熔体粘度降低。将含对羟基苯甲酸甲酯的挤出物的流变性能与含传统增塑剂的挤出物进行比较。发现对羟基苯甲酸甲酯在挤出过程中降低扭矩方面与柠檬酸三乙酯（TEC）一样有效。固态NMR光谱表明，用对羟基苯甲酸甲酯增塑的Eudragit RS PO的化学位移发生了变化，这可归因于对羟基苯甲酸甲酯的羟基与Eudragit RS PO聚合物的酯基之间的相互作用。本研究结果表明，在制备缓释片采用热熔挤出技术时，对羟基苯甲酸甲酯可作为Eudragit RS PO聚合物的固态增塑剂。
