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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)。
PVP K30 aqueous solution as a binder, the application of fluidized bed granulation technology step by step, were prepared containing the drug layer particles and the base layer particles, and then pressed double sustained-release tablets, and finally the tablets enteric coated with hydrochloric acid Pa Rossi enteric sustained release tablets. The reference drug (Paxil CR) was used as the control to investigate the release behavior of the two drugs in pH 1.0 hydrochloric acid, pH 7.5 Tris salt buffer, pH 6.0 phosphate buffer solution and water, respectively Similarity. The in vivo assay of Beagle dogs was established to investigate the in vivo pharmacokinetics of homemade enteric coated sustained-release tablets and reference preparations under the premise of similar release behavior (f_2> 50) After oral administration of paroxetine hydrochloride enteric-coated sustained-release tablets of Beagle dogs, the partial pharmacokinetic parameters of self-made products were as follows: t max 5.38 ± 3.25 h, c max 5.57 ± 3.81 ng / ml, t_ (3.59 ± 2.31) h, AUC_0 → t (38.34 ± 30.07) ng · ml ~ (-1) · h and MRT_0 → ∞ (7.51 ± 2.97) h respectively. The parameters of the reference formulation were as follows: t max (5.84 ± 6.74) ng / ml, t 1/2 (3.94 ± 2.67) h, AUC_0 → t (35.48 ± 39.45) ng · ml ~ (6.75 ± 7.15) · H, MRT_0 → ∞ (7.65 ± 3.64) h. The c_ (max) value of the self-made products was 121.90% of the corresponding parameters of the reference formulation. The main pharmacokinetic parameters t max, c max, AUC 0 → t after logarithmic conversion was no significant difference (P> 0.05), the relative bioavailability of homemade enteric coated tablets was 125.13% (geometric means).