【摘要】：目的:制備賴氨酸布洛芬緩釋液體栓劑,并進(jìn)行體內(nèi)外評價(jià)。方法:以泊洛沙姆溶液為主要基質(zhì)、卡波姆為生物黏附劑、月桂氮酮為滲透劑,制備賴氨酸布洛芬緩釋液體栓劑。以膠凝溫度、凝膠強(qiáng)度、生物黏附力及體外釋放度為指標(biāo)篩選泊洛沙姆407(P407)-泊洛沙姆188(P188)比例和卡波姆的含量,比較所制液體栓劑與普通固體栓劑經(jīng)直腸給藥后在Beagle犬體內(nèi)的藥-時(shí)曲線和藥動學(xué)參數(shù)。結(jié)果:處方中P407-P188比例為1∶1.2時(shí)緩釋液體栓劑的膠凝溫度為30.4~38.1℃,最接近直腸溫度;卡波姆含量為0.8%時(shí)緩釋液體栓劑的體外釋放符合零級方程,相關(guān)性最好(R~2=0.996)。普通固體栓的tmax為3.206 h,隨后血藥濃度下降明顯,緩釋時(shí)間不超過12 h,AUC_(0-∞)為501.826 mg·h/L;緩釋液體栓劑的t_(max)為8.814 h,隨后血藥濃度下降,緩釋時(shí)間超過24 h,AUC_(0-∞)為715.489 mg·h/L。結(jié)論:成功制得賴氨酸布洛芬緩釋液體栓劑,與普通固體栓劑比較其緩控釋效果更佳、體內(nèi)外相關(guān)性良好。
[Abstract]:Objective: to prepare lysine ibuprofen sustained-release liquid suppository and evaluate it in vivo and in vitro. Methods: Lysine ibuprofen sustained-release liquid suppository was prepared with Poloxamer solution as main matrix, carbomer as biological adhesive and lauroxone as osmotic agent. The ratio of Poloxamer 407 (P407) to Poloxamer 188 (P188) and the content of carbomer were screened by gel temperature, gel strength, bioadhesion and in vitro release. The pharmacokinetic parameters and pharmacokinetic parameters of liquid suppositories and general solid suppositories were compared in Beagle dogs after rectal administration. Results: the gelation temperature of sustained-release liquid suppository was 30.4 鈩，

本文編號：2352701