摘要
采用PVP K30的水溶液为黏合剂,应用流化床一步制粒技术,分别制备含药层颗粒与基座层颗粒,再压制双层缓释片,最后对素片进行肠溶包衣得盐酸帕罗西汀肠溶缓释片。以参比制剂(Paxil CR)为对照,分别考察在pH 1.0盐酸、pH 7.5 Tris盐缓冲液、pH 6.0磷酸盐缓冲液和水中的释放行为,以相似因子(f_2)评判二者体外释放行为的相似性。在4种介质中二者释放行为均相似的前提下(f_2>50),建立了Beagle犬体内分析方法,进一步探究自制肠溶缓释片与参比制剂的体内药动学特征,经过双周期交叉口服给予Beagle犬盐酸帕罗西汀肠溶缓释片后,自制品的部分药代参数如下:t_(max)(5.38±3.25)h,c_(max)(5.57±3.81)ng/ml,t_(1/2)(3.59±2.31)h,AUC_0→t(38.34±30.07)ng·ml^(-1)·h,MRT_0→∞(7.51±2.97)h;参比制剂的参数如下:t_(max)(6.75±7.15)h,c_(max)(5.84±6.74)ng/ml,t_(1/2)(3.94±2.67)h,AUC_0→t(35.48±39.45)ng·ml^(-1)·h,MRT_0→∞(7.65±3.64)h,自制品的c_(max)值为参比制剂相应参数的121.90%;二者主要药代动力学参数t_(max)、c_(max)、AUC_0→t经对数转换后无统计学差异(P>0.05),自制肠溶缓释片的相对生物利用度为125.13%(几何均值)。
In this paper, the preparation and in vitro-in vivo evaluation of paroxetine hydrochloride entericcoated sustained-release tablets were described. The analytical methods of paroxetine in vivo was developed and validated. The pharmacokinetic profiles of the home-made tablets and the reference listed drug （RLD）, Paxil CR, were characterized. The active layer granules and base layer granules were separately prepared by one-step granulation within a fluidized bed, where polyvinylpyrrolidone K30（PVP K30） aqueous solution was used as a binder. The granules were compressed into bilayer tablets, followed by coating with an enteric layer. The release behaviors of Paxil CR and homemade formulation in hydrochloric acid solution （pH 1.0）, Tris buffer solution （pH 7.5）, phosphate buffer solution （pH6.0） and water were recorded within 8 h and the similarity factor （f2） was calculated accordingly. It was shown that the release profiles of RLD and home-made formulation were similar. After double cross-over oral administration in Beagle dogs with paroxetine hydrochloride home-made formulation, the main pharmacokinetic parameters were as follows：tmax（5.38±3.25）h, cmax（5.57±3.81）ng/ml; t1/2（3.59±2.31）h, AUC0→t（38.34±30.07）ng·ml-1·h, MRT0→∞（7.51±2.97）h.Whereas, RLD was shown as follows： tmax（6.75±7.15）h, cmax（5.84±6.74）ng/ml, t1/2（3.94±2.67）h, AUC0→t（35.48±39.45）ng·ml-1·h, MRT0→∞（7.65±3.64）h. After the logarithmic conversion, the results showed that there were no significant difference in the parameters of tmax , cmax and AUC0→t （P〉0.05）. The relative bioavailability of the home-made tablets was 125.13%.
作者
曹焱
张国松
严轶东
陈勇
李东勲
CAO Yan ZHANG Guosong YAN Yidong CHEN Yong LI Dongxun(Jiangxi University of Traditonal Chinese Medicine, Nanehang 330004 Beijing Fogangren Bio-Pharma Ltd., Beijing 102628 School of Pharmacy, Nangtong University, Nangtong 226001)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第6期861-868,共8页
Chinese Journal of Pharmaceuticals
基金
江西省高等学校科技落地计划项目(KJLD13062)
江西省科技计划项目(2014BBG70082)
关键词
盐酸帕罗西汀
肠溶缓释片
体外释放
相似评价
药动学
paroxetine hydrochloride enteric-coated sustained-release tablet in vitro release similarity factor pharmacokinetics
