溢流式溶出法评价药物体外缓释性能的可行性研究

Study on the Feasibility of Evaluating Drug in vitro Sustained Release Performance by Overflow Dissolution Method

目的:研究溢流式溶出法用于评价药物体外缓释性能的可行性。方法:模拟体内药物的消除过程建立溢流式溶出法,以两个不同厂家的硝苯地平缓释片(Ⅰ)作为模型药物A、B,考察在溶出介质3种不同溢流速度(0、1.50、3.00 mL/min)下模型药物在释放池中的药-时曲线、累积释放度-时间曲线和释放速度-时间曲线。结果:溶出介质溢流速度为0时,药物的累积溶出度与常规溶出法结果一致;随着溢流速度增加,释放池中药物A、B的c_(max)均降低[A:(8.89±0.20)、(5.21±0.04)、(3.51±0.03)μg/mL;B:(7.62±0.05)、(4.80±0.09)、(2.89±0.04)μg/mL],累积释放度均增加[A:(85.47±2.45)%、(94.29±2.44)%、(96.04±2.56)%;B:(73.28±1.13)%、(78.46±1.94)%、(82.50±1.69)%],t_(max)均提前(A:1.5、1.0、0.5 h;B:2.0、1.0、0.5 h)。结论:溢流式溶出法避免了释放池中药物浓度过大对药物释放的抑制,使药物释放更完全,可更准确地评价制剂的体外缓释性能。

OBJECTIVE：To study the feasibility of overflow dissolution method for evaluating the drug in vitro sustained re-lease performance. METHODS：Overflow dissolution method was established by simulating the drugs elimination in vivo. Using Nifedipine sustained-elease tablets（Ⅰ）from 2 different manufacturers as model drug A,B,concentration-time curve,cumulative release rate- time curve,release velocity-time curve of model drugs in release pool at 3 different overflow speed （0,1.50,3.00 mL/min）were investigated. RESULTS：When overflow speed was 0,the cumulative dissolution was consistent with that of the con-ventional dissolution method. As the overflow speed increased,cmax of drug A,B was decreased [A：（8.89±0.20）,（5.21±0.04）, （3.51±0.03）μg/mL;B：（7.62±0.05）,（4.80±0.09）,（2.89±0.04）μg/mL];cumulative release rate was increased [A：（85.47± 2.45）%,（94.29 ± 2.44）%,（96.04 ± 2.56）%;B：（73.28 ± 1.13）%,（78.46 ± 1.94）%,（82.50 ± 1.69）%] ;tmax was ahead （A：1.5,1.0,0.5 h;B：2.0,1.0,0.5 h）. CONCLUSIONS：Overflow dissolution method has avoided the inhibition of too large drug concentration on drug release,making complete drug release and more accurate evaluation of in vivo sustained release performance of the preparation.