星点设计法优化布南色林-泊洛沙姆温敏水凝胶处方及含量测定

Formulation Optimization of Blonanserin-poloxamer Thermo-sensitive Gel via Central Composite Design and Determination

目的优化泊洛沙姆温敏水凝胶体系负载布南色林,并对凝胶中布南色林含量进行测定。方法采用直接混合法配备含药温敏水凝胶体系,倒置小管法测定胶凝温度(Tgel)。以Tgel为因变量,25%泊洛沙姆407体积(X1)、50%泊洛沙姆188体积(X2)和1%布南色林药物混悬液(X3)为考察因素,通过星点设计法优化制剂处方。采用高效液相串联质谱外标法测定凝胶中布南色林含量。结果随着泊洛沙姆407体积增加,Tgel呈下降趋势;泊洛沙姆188体积增加,Tgel呈增加趋势;最终选定处方(X1=3.7,X2=0,X3=0.45)。布南色林浓度在1~200 ng·m L^(-1)范围内线性良好,选择性(y=32 148.1x+6 066.60,R^(2)=0.999 3)、灵敏度、精密度、准确度均符合要求。水凝胶中布南色林浓度为(0.79±0.06) mg·mL^(-1)。结论本研究提供一种基于星点设计法优化布南色林-泊洛沙姆温敏水凝胶处方的方法,为难溶性药物通过温敏水凝胶体系实施缓释给药途径提供经验和思路。

OBJECTIVE To estabish a thermo-sensitive gel system for the delivery of blonanserin,and to determinatethe content of blonanserin in gel. METHODS Prepared blonanserin-poloxamer thermo-sensitive gel by direct mixing,and detected the gelation temperature( Tgel) through inverting the tube. The formulation of blonanserin-poloxamer thermo-sensitive gel was optimized by central composite design method.Tgel was set dependent variable,and volumes of 25% poloxamer 407( X1),50% poloxamer 188( X2) and 1%drug suspension( X3) were set as variables in the method.The content of blonanserin in gel was determined by high performance liquid coupled with mass spectrometry with external reference method. RESULTS The Tgel was descended with increasing volume of poloxamer 407,and was elevated with increasing volume of poloxamer 188. The optimal formulation was contained 3. 7 m L of 25%poloxamer 407 and 0.45 m L of 1% drug suspension in 5 mL. The content detection method of blonanserin in gel had good linearin the range of 1-200 ng·m L^(-1). The selectivity( y = 32 148. 1 x + 6 066. 60,R^(2)= 0. 999 3),precision and accuracy were met requirements. The concentration of blonanserin was( 0. 79 ± 0. 06) mg·mL^(-1) in gel. CONCLUSION This research provides a method for a formulation optimization method of blonanserin-poloxamer thermo-sensitive gel via central composite design,which can give experience for the sustained release of water-insoluble drug by thermo-sensitive gel.