无膜释放模型考察直肠用温敏型原位凝胶的体外释放情况

Investigation of Drug Release of Thermosensible In-situ Gels for Rectal Drug Delivery by Membraneless Dissolution Model in Vitro

目的:研究直肠用温敏型原位凝胶的体外释药考察方法。方法:采用无膜释放模型,以对乙酰氨基酚为模型药物、泊洛沙姆407为基质制备凝胶;分别采用《中国药典》桨法和常见的水浴振荡法,考察桨法转速(50、75、100r·min-1)、振荡器振荡频率(50、100、150r·min-1)对凝胶中药物释放行为的影响,并对释药数据采用不同的方程进行拟合。结果:桨法释药速率随桨速的增加而加快,但不同桨速间释药行为存在一定差异;振荡法释药速率也随振荡频率的增加而加快,但释药行为基本相似。各释药行为均符合零级方程,并以桨法75r·min-1和振荡法100r·min-1最符合。结论:本文建立的无膜释放模型可用于以泊洛沙姆407为基质的温敏型原位凝胶的释药研究,且桨法宜采用转速为75r·min-1,振荡法宜选用振荡频率为100r·min-1。

OBJECTIVE： To study the in vitro release of rectal therrnosensible in-situ gels. METHODS： A membraneless dissolution model was used for in vitro studies, and paracetamol was used as model drug. Poloxamer 407 was used as matrix to prepare gels. Both the paddle method according to Chinese Pharmacopeia and the water bath shaking method were used for the study, respectively. The effect of rotation speed （50, 75, 100 r.min-1） and shaking frequency （50, 100, 150 r.min l） on the in vitro drug release rate were studied for comparison. The drug release data was fitted using different equations. RESULTS： According to the membraneless dissolution model, the release rate was increased with the increase of the paddle speed and the shaking frequency. The release profiles among each other were similar by shaking method but not by paddle method. According to relative coefficients, the paddle method with 75 r. min 1 and the shaking method with 100 r. min-1 fitted with zero order equation well. CONCLUSION： The membraneless dissolution model could be used for drug release study of thermosensible in-situ gels using poloxamer 407 as matrix. The optimal condition is 75 r.min-1 for the paddle method, while 100 r.min-1 for the shaking method. KEY WORDS