Chaves Luíse L, Vieira Alexandre C C, Ferreira Domingos, Sarmento Bruno, Reis Salette
UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Laboratório de Tecnologia Farmacêutica, Departamento de Ciêncas do Medicamento, Faculdade de Farmácia, Universidade do Porto, Portugal.
Int J Biol Macromol. 2015 Nov;81:662-71. doi: 10.1016/j.ijbiomac.2015.08.009. Epub 2015 Aug 24.
This work aimed to design dapsone (DAP) amorphous Polymeric Dispersions (PD) using design of experiments (DoE) and response surface methodology (RSM) as optimization tools in order to tailor the biopharmaceutical properties toward its oral delivery. A two-factor, three-level (3(2)) statistical design was implemented to study the influence of input variables (amount of PVP K30 and Pluronic F68) on the equilibrium solubility of DAP of the physical mixture (PM), kneaded (KN) and freeze dried (FD) PDs. Through the analysis, it was found that equilibrium solubility of DAP was improved with increasing of PVP K30, mainly for FD PDs, but decreased with increasing Pluronic F68 concentration. XRD and FTIR spectrum revealed the amorphous characteristic of FD PDs and SEM confirmed the homogeneity of the system leading to enhanced surface area and consequent dissolution rate. The in vitro dissolution rate of PDs was significantly faster compared to DAP and PM, and all the similarity factors (f2) were below 50, demonstrating the differences on the dissolution profiles. The results established the effectiveness of PDs for improvement of dissolution and solubility of DAP and the success in the implementation of DoE and RSM as QbD tools in the design of PDs.
本研究旨在利用实验设计（DoE）和响应面法（RSM）作为优化工具来设计氨苯砜（DAP）无定形聚合物分散体（PD），以调整其口服给药的生物药剂学性质。采用两因素三水平（3(2)）统计设计，研究输入变量（聚乙烯吡咯烷酮K30（PVP K30）和普朗尼克F68（Pluronic F68）的用量）对物理混合物（PM）、捏合（KN）和冷冻干燥（FD）PDs中DAP平衡溶解度的影响。通过分析发现，随着PVP K30用量的增加，DAP的平衡溶解度提高，主要是对于FD PDs，但随着Pluronic F68浓度的增加而降低。X射线衍射（XRD）和傅里叶变换红外光谱（FTIR）显示了FD PDs的无定形特征，扫描电子显微镜（SEM）证实了体系的均匀性，导致表面积增加，进而溶解速率提高。与DAP和PM相比，PDs的体外溶解速率明显更快，所有相似因子（f2）均低于50，表明溶解曲线存在差异。结果证实了PDs在改善DAP的溶解和溶解度方面的有效性，以及在PDs设计中成功实施DoE和RSM作为质量源于设计（QbD）工具。
