Bile salt/lecithin mixed micelles optimized for the solubilization of a poorly soluble steroid molecule using statistical experimental design
Bile salt/lecithin mixed micelles optimized for the solubilization of a poorly soluble steroid molecule using statistical experimental design
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DOI：
10.1081/ddc-120018379
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发表时间：
2003-01-01
影响因子：
3.4
通讯作者：
Luscombe, C
中科院分区：
文献类型：
--
作者：
Magee, GA;French, J;Luscombe, C
胆汁盐和卵磷脂在生理上结合联合收割机形成混合胶束，有助于膳食脂肪和药物分子的溶解和吸收。在这一系列实验中，我们已经展示了实验设计程序如何帮助优化将胆汁盐、卵磷脂和水与丙酸氟替卡松（FP）作为模型难溶性药物的制剂。最初纳入的分类变量排除了经典响应面设计的使用;因此，使用从所有可能的实验组合的候选集中选择的d-最优选择构建实验设计。使用单独的2因素中心复合设计确定：在消除分类变量后，在扩展范围内的最佳卵磷脂和胆盐浓度。已经证明，卵磷脂或胆酸浓度的增加导致FP的溶解度增加，而与其他两种胆汁盐相比，牛磺胆酸钠似乎抑制FP的溶解度。FP溶解度与制剂中总脂质之间的线性关系进一步证明了与胆汁盐和卵磷脂增加相关的溶解度增加。处方中卵磷脂与胆汁盐的摩尔比的影响也是显著的。混合胶束系统的物理性质（溶液浊度和粘度等级）用于进一步区分制剂。优化结果表明，优化后的优化效果最优。是卵磷脂，其随着浓度的增加而改善制剂的增溶特性。盐浓度的影响不太明显，但在性质上略有平方。所证明的溶解度的总体增加是从
Bile salts and lecithin combine physiologically to form mixed micelles which aid the solubilization and absorption of dietary fats and drug molecules. In this series of experiments, we have shown how experimental design procedures aid the optimization of a formulation incorporating a bile salt, lecithin, and water with fluticasone propionate (FP) as the model poorly soluble drug. The initial inclusion of a categorical variable ruled out the use of classic response surface designs; therefore the experimental design was constructed using a d-optimal selection from a candidate set of all possible experimental combinations. A separate 2-factor central composite, design was used to determine the: optimum lecithin and bile salt concentrations over an extended range after the categorical variable had been eliminated. It has been demonstrated that an increase in either lecithin or cholic acid concentration produces an increase in solubility of FP, while sodium taurocholate appears to depress the solubility of FP compared with the other two bile salts. The increase in solubility associated with the increase in bile salt and lecithin is further demonstrated by a linear relationship between FP solubility and the total lipid in the formulation. The influence of molar ratio of lecithin to bile salt in the formulation is also significant. The physical properties of the mixed micellar system (solution turbidity and viscosity ranking) were used to further discriminate between formulations. The optimization showed that the dominant effect. was the lecithin, which improves the solubilizing characteristics of the formulation with increasing concentration. The effect of salt concentration is less marked though slightly quadratic in nature. The overall increase in solubility demonstrated was from