Streubel A, Siepmann J, Bodmeier R
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Int J Pharm. 2002 Jul 25;241(2):279-92. doi: 10.1016/s0378-5173(02)00241-7.
The aim of this study was to develop a novel multiparticulate gastroretentive drug delivery system and to demonstrate its performance in vitro. Floating microparticles consisting of (i) polypropylene foam powder; (ii) verapamil HCl as model drug; and (iii) Eudragit RS, ethylcellulose (EC) or polymethyl methacrylate (PMMA) as polymers were prepared with an O/W solvent evaporation method. The effect of various formulation and processing parameters on the internal and external particle morphology, drug loading, in vitro floating behavior, in vitro drug release kinetics, particle size distribution and physical state of the incorporated drug was studied. The microparticles were irregular in shape and highly porous. The drug encapsulation efficiency was high and almost independent of the theoretical loading. Encapsulation efficiencies close to 100% could be achieved by varying either the ratio 'amount of ingredients: volume of the organic phase' or the relative amount of polymer. In all cases, good in vitro floating behavior was observed. The release rate increased with increasing drug loading and with decreasing polymer amounts. The type of polymer significantly affected the drug release rate, which increased in the following rank order: PMMA<EC<Eudragit RS. A broad spectrum of release patterns could be obtained with the investigated formulations. In contrast, the effect of the volume of the aqueous phase on drug release was not very pronounced. The size of the microparticles was almost independent of the drug loading, but strongly depended on the amount of polymer. The drug was partly dissolved and partly in the amorphous form distributed throughout the system.
本研究的目的是开发一种新型的多颗粒胃滞留药物递送系统，并在体外证明其性能。采用水包油溶剂蒸发法制备了由（i）聚丙烯泡沫粉末；（ii）盐酸维拉帕米作为模型药物；以及（iii）Eudragit RS、乙基纤维素（EC）或聚甲基丙烯酸甲酯（PMMA）作为聚合物组成的漂浮微粒。研究了各种制剂和工艺参数对内部和外部颗粒形态、载药量、体外漂浮行为、体外药物释放动力学、粒径分布以及所含药物物理状态的影响。微粒形状不规则且高度多孔。药物包封效率高，且几乎与理论载药量无关。通过改变“成分量:有机相体积”的比例或聚合物的相对量，可实现接近100%的包封效率。在所有情况下，均观察到良好的体外漂浮行为。释放速率随载药量增加和聚合物用量减少而增加。聚合物类型显著影响药物释放速率，其增加顺序如下：PMMA＜EC＜Eudragit RS。在所研究的制剂中可获得广泛的释放模式。相比之下，水相体积对药物释放的影响不太明显。微粒大小几乎与载药量无关，但强烈依赖于聚合物的用量。药物部分溶解，部分以无定形形式分布于整个系统中。
