Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

采用挤出滚圆法制备了含10%（w/w）药物的氢溴酸右美沙芬（Dextromethorphan hydrobromide，DM）缓释骨架微丸。本研究采用混合扭矩流变仪（mixer torque rheometry，MTR），考察了乙基纤维素（ethyl cellulose，EC）、羟丙基甲基纤维素（hydroxypropyl methylcellulose，HPMC K10）与卡波姆934（Carbopol 934）分别与微晶纤维素PH101（Avicel PH101）按不同浓度配比复配时，对微丸湿物料流变学特性的影响。对所制备的微丸开展粒径、药物含量及体外DM释放速率的表征分析。研究结果表明：与微晶纤维素PH101复配时，疏水聚合物EC浓度升高会降低湿物料稠度，该特性以湿物料平均线扭矩表征；此时实现最优湿法制粒所需的黏合剂比例更低。而当体系与溶胀性聚合物（HPMC与卡波姆）复配时，平均线扭矩与黏合剂比例均出现显著升高。高浓度的HPMC与卡波姆复配处方，可实现DM从微丸中的体外控释。进一步对微丸的体外释药数据进行数学处理后发现，除含5%卡波姆+5%HPMC的处方（F10）外，其余所有制剂均符合一级释药动力学规律。此类制剂的n值处于0.09~0.40区间，证实其释药行为属于反常非菲克释药。