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目的 以盐酸普罗帕酮为模型药物 ,采用离体羊鼻黏膜渗透实验与在体大鼠鼻腔灌流实验 ,探讨鼻黏膜吸收的影响因素 ,并进行体外法与在体法的相关性的考查。方法 通过改变介质 pH值、药物浓度、制成 β 环糊精包合物等方法改变药物的理化性质 ,测定不同条件下药物透过离体羊鼻黏膜的渗透系数Pm、平均渗透速度或透过分数 ,测定相应条件下在体大鼠鼻腔黏膜吸收速度常数k、平均吸收速度或吸收分数 ,并应用体外法实验与在体法实验中提取的参数进行相关性检验。结果 药物的浓度、介质的 pH值以及环糊精包合物的形成等理化因素 ,对其体外法和在体法透膜均有很大影响。在本研究的各种条件下 ,体外法与在体法实验均有很好的相关性。结论 本研究对于正确评价鼻腔吸收体外与在体实验方法 ,完善和发展鼻腔吸收的系统研究方法提供了确切的实验依据。
OBJECTIVE To investigate the influence factors of nasal mucosa absorption by using propafenone hydrochloride as model drug in vitro and nasal mucosa infiltration in vitro and nasal perfusion in vivo in rats and investigate the correlation between in vitro and in vivo methods. Methods The physical and chemical properties of drugs were changed by changing the medium pH value, drug concentration, β-cyclodextrin inclusion complex and so on. The permeation coefficient Pm, average penetration velocity or permeation rate of the drug through the isolated sheep nasal mucosa were measured under different conditions , The nasal mucosa absorption rate constant k, the average absorption rate or absorption fraction of the rats in the corresponding conditions were determined, and the correlation test was conducted between the in vitro method and the parameters extracted in the body method. Results The physical and chemical factors such as the concentration of drug, the pH value of the medium and the formation of cyclodextrin inclusion complex have a great influence on the in vitro and in vivo transdermal systems. Under the various conditions of this study, in vitro methods and in vivo experiments have a good correlation. CONCLUSIONS This study provides an accurate experimental evidence for a systematic evaluation of nasal absorption in vitro and in vivo, and for the improvement and development of nasal absorption.