普罗帕酮缓释制剂研制及体外溶出度试验研究

The Trituration of Slow-released Microcapsule Propafenone and Test of Ist Solubility in Vitro

目的 普罗帕酮 ( Propafenone)是一种有效的抗心律失常药物 ,但血药峰浓度时副作用较大 ,有明显的肝脏首过效应 ,为降低副作用 ,并减少给药次数 ,又维持平稳有效的血药浓度 ,达到抗心律失常缓释长效治疗目的 ,而研制普罗帕酮缓释微囊。方法 采用单凝聚法 ,以明胶为囊材 ,将普罗帕酮制成缓释微囊。结果 微囊包囊率为 74± 0 .64 % ,稳定性良好 ,体外溶出度测定 2 40 min,溶出 94.65 %。通过 Weithull分布模型处理得出微囊和片剂释放参数分别为 :m (形状参数 ) :1.0 11和 0 .93 2 ;T50 :48.10± 2 .0 2 min和 13 .8± 2 .19min;Td:69.2 2± 0 .76min和 2 0 .41±3 .11min。将二者进行 t值检验 ,P<0 .0 1,表明普罗帕酮微囊具有显著的缓释作用。结论 普罗帕酮微囊具有显著平稳缓释药物作用 ,达到抗心律失常缓释长效的治疗目的。

OBJECTIVE Propafenone is one of effective anti-arrhythmia drugs, but it has bigger side-effect when its concentration in blood reaches its peak, which appears obviously at its first time pass liver. In order to reduce the side-effect, the times of taking the drug and maintaining the effective concentration of the drug in blood to achieve the successof the first-treatment with this slow-released drug, we triturated the slow-released microcapsule propafenone.METHODS the propafenone was made to be slow-released microcapsule by using gelatin as the materials for capsulsule,and the method used was so-called single agglutionation.RESULTS the encapsulated rate of the microcapsule was 74±0.64% with good stability. The solubility in vitro that had been measured for a total 240min was 94.65%. The results obtained by the distribution mode of Weithnull showed that the slow-released parameter of microcapsule and tablet were m(shape parameter):1.011 and 0.932;T 50 :48.10±2.02 min and 13.8±2.19min; Td:69.22±0.76 min and 20.41±3.11 min,respectively. The t-value test for the microcapsule and tablet showed P<0.01, indicating that there was significant difference between the two same drugs with different shapes, and the slow-released microcapsule propafenone had significant slow-released effect.CONCLUSION the microcapsule propafenone has the stable slow-released drug effect and reaches the standards of long-acting treatment for anti-arrhythmia.