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水基聚合物分散体:用于筛选阿替洛尔胃肠治疗系统制剂变量的Plackett-Burman设计

Aqueous based polymeric dispersion: Plackett--Burman design for screening of formulation variables of atenolol gastrointestinal therapeutic system.

作者信息

Sastry S V, Khan M A

机构信息

Division of Basic Pharmaceutical Sciences, School of Pharmacy, Northeast Louisiana University, Monroe 71209, USA.

出版信息

Pharm Acta Helv. 1998 Jul;73(2):105-12. doi: 10.1016/s0031-6865(97)00052-6.

Abstract

Bilayered osmotically controlled Gastrointestinal Therapeutic System of atenolol has been obtained by using cellulose acetate pseudolatex prepared by polymer emulsification method. Various factors such as orifice size, coating thickness, amount and nature of polymeric excipients, and amount of osmotic agent influence the drug release from GITS. Therefore, in the present study a 7-factor, 12-run Plackett-Burman screening design was employed to evaluate the formulation variables for atenolol GITS coated with CA pseudolatex. The variables studied were orifice size, %coating weight gain, amounts of sodium chloride. Polyox N80 and 303, and Carbopol 934P and 974P on drug release. The screening design has revealed that orifice size, %coating weight gain and amount of Carbopol 934P have prominent influence on in-vitro atenolol release. The response variable was cumulative percent atenolol released (Y) in 24 h with constraints on percent release at 2, 6, 12 and 18 h. The polynomial equation obtained was Y24 = 149.82 - 0.13 X1 - 0.34X2 + 0.06X3 - 0.13X4 - 0.23X5 - 76.25X6 - 2.46X7. The results indicated that the drug release under constrained conditions was influenced by the factors with decreasing order of importance as %coating weight gain > Carbopol 934P > Polyox N80 > Carbopol 974P > Polyox 303 > amount of sodium chloride > orifice size.

摘要

采用聚合物乳化法制备的醋酸纤维素假胶乳,获得了阿替洛尔双层渗透控释胃肠道治疗系统。诸如孔径、包衣厚度、聚合物辅料的用量和性质以及渗透剂用量等多种因素会影响药物从胃肠道治疗系统中的释放。因此,在本研究中,采用七因素、十二次运行的Plackett-Burman筛选设计来评估用醋酸纤维素假胶乳包衣的阿替洛尔胃肠道治疗系统的处方变量。所研究的变量包括孔径、包衣增重百分比、氯化钠、聚氧化乙烯N80和303、卡波姆934P和974P的用量对药物释放的影响。筛选设计表明,孔径、包衣增重百分比和卡波姆934P的用量对阿替洛尔体外释放有显著影响。响应变量为24小时内阿替洛尔累积释放百分比(Y),并对2、6、12和18小时的释放百分比有所限制。得到的多项式方程为Y24 = 149.82 - 0.13X1 - 0.34X2 + 0.06X3 - 0.13X4 - 0.23X5 - 76.25X6 - 2.46X7。结果表明,在受限条件下药物释放受各因素的影响,其重要性递减顺序为:包衣增重百分比>卡波姆934P>聚氧化乙烯N80>卡波姆974P>聚氧化乙烯303>氯化钠用量>孔径。

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