摘要
本文研究了硝苯啶骨架型贴膜剂经皮吸收的可行性。建立了测定体内和体外硝苯啶药物浓度的高液效相色谱法。两种处方的贴膜剂(R_1未加增渗剂,R_2加有月桂氮酮作为增渗剂)的体外经皮渗透实验表明:硝苯啶以零级动力学方式渗透皮肤,但在10.25 h前后释放速率不同,R_1分别为2.63及1.1μg/cm^2.h,R_2分别为4.30及1.5μg/cm^2·h。由R_2贴膜剂的释放实验确定:硝苯啶从药库基质中的释放符合t^(1/2)型释放过程,释放速度常数为68.91μg/cm^2·t^(1/2)。健康受试者五名贴用R_2贴膜剂1.5 h后达到稳态血浓,并在24.5h内保持治疗范围内的血药浓度(10～100 mg/ml),本文还对硝苯啶贴膜的质量进行了多方面的考察。
The feasibility of matrix dispersion- type nifedipine patch was verified and an HPLC method for the determination of nifedipine level both in vitro and in vivo was established.It was found that both the two formulations of the patch (R_2 with azone as penetration enhancer, R_1 without azone) provided zero order kinetics of permeation, the rates of skin permeation were different at <10.25 and> 10.25h, R_1 was 2.63 and 1.1 μg/cm^2· h ; R_2 was 4.30 and 1.54μg/cm^2· h. The release profiles of nifedipine from R_2 were found to follow a linear Q vs t^(1/2) relationship with a release flux of 68.91μg/cm^2·h^(1/2). The plasma concentration vs time profiles of nifedipine in healthy subjects, each receiving two patches (36×2 cm^2), were investigated. A steady state plasma level within therapeutic concentration window was obtained from 1.5 h to 24. 5 h. Several quality tests of the patch were evaluated in this research.
出处
《药学学报》
CAS
CSCD
北大核心
1991年第4期286-292,共7页
Acta Pharmaceutica Sinica
关键词
硝苯啶
贴膜剂
Nifedipine
Patch
Percutaneous absorption
HPLC
Azone
