利培酮缓释片的体外释放度及其在家兔体内的药动学研究
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篇名: 利培酮缓释片的体外释放度及其在家兔体内的药动学研究
TITLE:
摘要: 目的:研究利培酮缓释片的体外释药行为及其在家兔体内的药动学。方法:以介孔二氧化硅为骨架制备利培酮缓释片。采用篮法考察市售利培酮片、利培酮缓释片及其物理混合物在0.1 mol/L盐酸中12 h内的体外释放度(Q12 h),并对利培酮缓释片释药模型进行拟合。以氯氮平为内标,采用高效液相色谱法测定家兔灌胃市售利培酮片和利培酮缓释片各2 mg后48 h内利培酮和9-羟基利培酮的血药浓度(n=6),并用Kinetica 4.4软件的非房室模型分析,计算药动学参数。结果:与市售利培酮片(Q12 h=97%)和物理混合物(Q12 h=95%)比较,利培酮缓释片的释放速率明显减慢(Q12 h=83.7%),利培酮缓释片在0.1 mol/L盐酸中的释放更接近于一级释放(R2=0.998 9),以扩散为主、溶蚀为辅。市售利培酮片和利培酮缓释片在家兔体内的药动学参数:以利培酮计t1/2为(4.64±0.93)、(6.65±0.92)h,cmax为(34.46±7.75)、(8.57±6.91) ng/mL,MRT为(11.48±1.23)、(17.46±2.10)h,AUC0-48 h为(314.39±10.33)、(192.98±49.14) ng·h/mL;以9-羟基利培酮计t1/2为(7.08±0.93)、(10.45±0.78) h,cmax为(98.08±5.43)、(54.55±4.88) ng/mL,MRT为(11.48±1.23)、(17.46±2.10) h,AUC0-48 h为(894.71±131.15)、(1 227.99±112.12) ng·h/mL(n=6)。与市售利培酮片比较,利培酮缓释片的t1/2和MRT明显延长,cmax明显降低(P<0.05)。结论:利培酮经介孔二氧化硅负载后具有缓释作用,可延长药效发挥的时间。
ABSTRACT: OBJECTIVE: To study release behavior in vitro of Risperidone sustained-release tablets and its pharmacokinetics in rabbits. METHODS: Risperidone sustained-release tablets were prepared by using mesoporous silica as matrix. Release rates in vitro within 12 h (Q12 h) of commercially available Risperidone tablets, Risperidone sustained-release tablets and its physical mixture in 0.1 mol/L HCl fluid were investigated with basket method. The release model of Risperidone sustained-release tablets were fitted. Using clozapine as an internal standard, HPLC method was used to determine blood concentration of risperidone and 9-hydroxyrisperidone in rabbits 48 h (n=6) after intragastric administration of commercially available Risperidone tablets and Risperidone sustained-release tablets 2 mg. Pharmacokinetic parameters were calculated by using non-compartmental model of Kinetica 4.4 software. RESULTS: Compared with commercially available Risperidone tablets (Q12 h=97%) and physical mixtures (Q12 h=95%), release rate of Risperidone sustained-release tablets (Q12 h=83.7%) slowed down significantly, and the release of Risperidone sustained-release tablets in 0.1 mol/L HCl fluid was closed to first-order release (R2=0.998 9), with diffusion as the main factor and dissolution as the supplement. By risperidone, the pharmacokinetic parameters of commercially available Risperidone tablets and Risperidone sustained-release tablets included that t1/2 were (4.64±0.93),(6.65±0.92) h; cmax were (34.46±7.75) and (8.57±6.91) ng/mL; MRT were (11.48±1.23), (17.46±2.10) h; AUC0-48 h were (314.39±10.33),(192.98±49.14) ng·h/mL, respectively. By 9-hydroxyrisperidone, the pharmacokinetic parameters of them included that t1/2 were(7.08±0.93),(10.45±0.78) h; cmax were (98.08±5.43),(54.55±4.88) ng/mL; MRT were (11.48±1.23), (17.46±2.10) h; AUC0-48 h were (894.71±131.15), (1 227.99±112.12) ng·h/mL (n=6), respectively. Compared with commercially available Risperidone tablets, t1/2 and MRT of Risperidone sustained-release tablets prolonged significantly, while cmax decreased significantly (P<0.05). CONCLUSIONS: Risperidone loaded in mesoporous silica has sustained release effect and prolong the time of drug efficacy.
期刊: 2019年第30卷第15期
作者: 王敏,王倩,李春霞,沈雁,孙益新
AUTHORS: WANG Min,WANG Qian,LI Chunxia,SHEN Yan,SUN Yixin
关键字: 介孔二氧化硅;利培酮;缓释片;释放度;药动学;家兔
KEYWORDS: Mesoporous silica; Risperidone; Sustained- release tablets;Release rate; Pharmacokinetics; Rabbit
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