Seth Avinash Kumar, Misra Ambikanandan
Pharmacy Department, Faculty of Engineering & Technology, Maharaja Sayajirao University, Baroda, India.
J Pharm Pharm Sci. 2002 Sep-Dec;5(3):285-91.
The aim of this study was to derive simple reduced second order polynomial equation for constructing contour plots to obtain predetermined % drug entrapment (PDE) within liposomes of acyclovir (ACY) when prepared by reverse phase evaporation (REV) method using technique of three variables at three levels (3(3)) factorial design.
Three independent variables selected were volume of organic phase (x(1)), volume of aqueous phase (x(2)), and Drug/Phosphatidylcholine (PC) /Cholesterol (CHOL) in molar ratio (x(3)). Based on factorial design, twenty-seven batches of ACY liposomes were prepared by REV method. Prepared liposomal batches were evaluated for size, lamellarity, and PDE. The PDE (dependent variable) and the transformed values of independent variables were subjected to multiple regressions to establish a second order polynomial equation (full model). To simplify the equation, F-statistic was applied to reduce polynomial equation (reduced model) by neglecting nonsignificant (p>0.05) terms. The coefficient value for independent variable, Drug/PC/CHOL in molar ratio (x(3)) was found to be maximum (b(3) = 2.52) and hence the variable x(3) was considered to be a major contributing variable for PDE within liposomes by REV method. The reduced polynomial equation was used to plot three two-dimensional contour plots at a fixed levels of -1, 0 and 1 of major contributing variable (x(3)) to obtain various combinations of values of two other independent variables (x(1) & x(2)) at predetermined PDE. The conformity of the established equation was checked by preparing three batches three times taking values of the independent variables from the contour plots for prefixed value of PDE.
Prefixed PDE value taken for designing the experiment and results obtained experimentally were compared using student 't' test and difference between experimentally obtained and theoretically calculated values of PDE was found to be statistically nonsignificant (p>0.05).
Findings of this study establishes the role of the derived equation and plotted contour plots in predicting the values of independent variables for preparation of ACY liposomes by REV method having predetermined PDE.
本研究的目的是推导一个简化的二阶多项式方程,用于构建等高线图,以便在采用三变量三水平(3(3))析因设计技术通过反相蒸发(REV)法制备阿昔洛韦(ACY)脂质体时,获得预定的药物包封率(PDE)。
选择的三个自变量分别为有机相体积(x(1))、水相体积(x(2))以及药物/磷脂酰胆碱(PC)/胆固醇(CHOL)的摩尔比(x(3))。基于析因设计,通过REV法制备了27批ACY脂质体。对制备的脂质体批次进行大小、层数和PDE评估。将PDE(因变量)和自变量的转换值进行多元回归以建立二阶多项式方程(全模型)。为简化方程,应用F统计量通过忽略无显著性(p>0.05)的项来简化多项式方程(简化模型)。发现自变量药物/PC/CHOL的摩尔比(x(3))的系数值最大(b(3)=2.52),因此变量x(3)被认为是REV法制备脂质体时PDE的主要影响变量。简化的多项式方程用于在主要影响变量(x(3))的固定水平-1、0和1下绘制三个二维等高线图,以获得预定PDE下另外两个自变量(x(1)和x(2))值的各种组合。通过制备三批样品三次,从等高线图中获取自变量值用于预定PDE的固定值,来检验所建立方程的符合性。
使用学生t检验比较了设计实验时采用的预定PDE值和实验获得的结果,发现PDE的实验值与理论计算值之间的差异无统计学显著性(p>0.05)。
本研究结果确立了推导方程和绘制的等高线图在预测采用REV法制备具有预定PDE值的ACY脂质体时自变量值方面的作用。