自制奥昔布宁渗透泵控释片的体内外相关性研究

In vitro and in vivo correlation of self-designed osmotic pump tablet of oxybutynin

目的:研究自制奥昔布宁渗透泵控释片在体内外的相关性。方法:以HPLC法(Irregular H C18 柱,4.6 mm×150mm,流动相为甲醇∶水∶1 mol/L醋酸铵=85∶13∶2,流速为1.0 ml/min,检测波长220 nm)测定奥昔布宁渗透泵控释片体外释放浓度(释放介质:200 ml 蒸馏水,37℃,转速:100 r/min,分别在2、4、8、12、16、24 h各取样1 ml),用LC MS法测定渗透泵控释片在Beagle犬体内的血药浓度(8条犬禁食过夜后口服自制奥昔布宁渗透泵片10 mg,于给药前及给药后2.5、5.0、8.0、12.0、16.0、24.0、27.0、30.0、36.0、48.0 h在犬一侧后肢静脉取血1 ml分离血浆待测),用Wanger Nelson法计算体内吸收百分数,并与相应时间体外累积溶出度线性回归,进行体内外相关性考察。结果:药物恒速释放达24 h,累积释放率达90%以上。体内药动学特征符合单室一级吸收模型,血药浓度在48 h内表现平稳。以体内吸收百分率(Y)与体外释放百分率(X)进行线性回归,方程如下:Y=0.978 2X+12.501 9,r=0.937 3 (P<0.01)。结论:自制奥昔布宁渗透泵控释片体外释放百分率和体内吸收百分率呈显著相关。

Objective:To study the in vitro and in vivo correlation of self-designed oxybutynin osmotic pump tablet. Methods: Oxybutynin was assayed by HPLC in vitro and by LC-MS in vivo. HPLC methods were used:Irregular-H C18 column, 4.6 mm× 150 mm; mobile phase was methanol∶water∶1 mol/L ammonium acetate=85∶13∶2; flow rate 1.0 ml/min,UV detective wavelength 220 nm.The condition of dissolution study was as follows: dissolution media 200 ml distilled water,temperature 37℃,stir rate 100 r/min,sample time 2,4,8,12,16,24 h,sample volume 1 ml. Eight dogs received oral adminstration of oxybutynin osmotic pump tablet (10 mg) and sampling times were 0,2.5,5.0,8.0,12.0,16.0,24.0,27.0,30.0,36.0,48.0 h.The correlation was studied by the test of the dissolution in vitro and the pharmacokinetics in vivo through Wanger-Nelson method.Results: The drug was released from OPT at a controlled rate for over 24 h,and the cumulative release at 24 h was over 90%. Self-prepared OPT coincided with one-compartment model and provided a persistent plasma level for at least 24 h. The linear regressive equation was established between the absorption rate in vivo and the accumulating dissolution rate in vitro of oxybutynin as Y=0.978 2X+12.501 9(P<0.01).Conclusion:There is a significant correlation between the absorption in vivo and the dissolution in vitro of oxybutynin osmotic pump tablet.