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Computer-Aided Formulation Design for a Highly Soluble Lutein–Cyclodextrin Multiple-Component Delivery System
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00056 Qianqian Zhao 1 , Nikhila Miriyala 2 , Yan Su 1 , Weijie Chen 1 , Xuejiao Gao 1 , Ling Shao 1 , Ru Yan 1 , Haifeng Li 3 , Xiaojun Yao 4 , Dongsheng Cao 5 , Yitao Wang 1 , Defang Ouyang 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00056 Qianqian Zhao 1 , Nikhila Miriyala 2 , Yan Su 1 , Weijie Chen 1 , Xuejiao Gao 1 , Ling Shao 1 , Ru Yan 1 , Haifeng Li 3 , Xiaojun Yao 4 , Dongsheng Cao 5 , Yitao Wang 1 , Defang Ouyang 1
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Cyclodextrin (CD) complexation is widely used for the solubilization of poorly soluble drugs in the pharmaceutical industry. Current research was to develop a highly soluble lutein–cyclodextrin multiple-component delivery system (lutein–CD-MCDS) by combined modeling and experimental approaches. Both phase solubility diagram and molecular dynamics (MD) simulation results revealed that the interactions between lutein and CDs were very weak, which confirmed the insignificant solubility improvement of lutein–CD binary system. On the basis of theoretical calculation and preliminary CD studies, lutein–CD-MCDS was developed with over 400-fold solubility improvement after formulation screening. MD simulation indicated that the auxiliary polymers of TWEEN 80 and poloxamer 188 in the lutein–CD-MCDS introduced bridged interaction between lutein and γ-CD to increase the solubility, dissolution rate, and stability of the complex. The lutein–CD-MCDS was characterized by in vitro dissolution test, differential scanning colorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD). Moreover, lutein–CD-MCDS had significantly higher uptake in Caco-2 cells than free lutein. The relative bioavailability of the lutein–CD-MCDS increased to 6.6-fold compared to pure lutein, and to 1.2-fold compared with commercial lutein soft capsules. In conclusion, the highly soluble lutein–CD-MCDS with significant improvement in both the solubility and bioavailability was developed and characterized by combined modeling and experimental approaches. Our research indicates that computer-aided formulation design is a promising approach for future formulation development.
中文翻译：
高溶解性叶黄素-环糊精多组分递送系统的计算机辅助配方设计
环糊精（CD）络合被广泛用于制药行业中难溶性药物的增溶。当前的研究是通过结合建模和实验方法来开发一种高度溶解的叶黄素-环糊精多组分递送系统（叶黄素-CD-MCDS）。相溶解度图和分子动力学（MD）模拟结果均表明，叶黄素与CD之间的相互作用非常弱，这证实了叶黄素-CD二元体系的溶解度改善不明显。在理论计算和初步CD研究的基础上，开发了叶黄素CD-MCDS，经过筛选后，溶解度提高了400倍以上。MD模拟表明，叶黄素-CD-MCDS中的TWEEN 80和泊洛沙姆188的辅助聚合物在叶黄素和γ-CD之间引入了桥连作用，从而增加了复合物的溶解度，溶解速率和稳定性。叶黄素-CD-MCDS的特征在于体外溶出度测试，差示扫描比色法（DSC），傅立叶变换红外光谱（FT-IR），扫描电子显微镜（SEM）和粉末X射线衍射（PXRD）。此外，叶黄素-CD-MCDS在Caco-2细胞中的摄取明显高于游离叶黄素。与纯叶黄素相比，叶黄素-CD-MCDS的相对生物利用度增加到6.6倍，而与市售叶黄素软胶囊相比则增加到1.2倍。总之，开发了高溶解性叶黄素-CD-MCDS，其溶解度和生物利用度均得到了显着改善，并通过组合建模和实验方法进行了表征。我们的研究表明，计算机辅助配方设计是未来配方开发的一种有前途的方法。
更新日期：2018-03-05
中文翻译：
高溶解性叶黄素-环糊精多组分递送系统的计算机辅助配方设计
环糊精（CD）络合被广泛用于制药行业中难溶性药物的增溶。当前的研究是通过结合建模和实验方法来开发一种高度溶解的叶黄素-环糊精多组分递送系统（叶黄素-CD-MCDS）。相溶解度图和分子动力学（MD）模拟结果均表明，叶黄素与CD之间的相互作用非常弱，这证实了叶黄素-CD二元体系的溶解度改善不明显。在理论计算和初步CD研究的基础上，开发了叶黄素CD-MCDS，经过筛选后，溶解度提高了400倍以上。MD模拟表明，叶黄素-CD-MCDS中的TWEEN 80和泊洛沙姆188的辅助聚合物在叶黄素和γ-CD之间引入了桥连作用，从而增加了复合物的溶解度，溶解速率和稳定性。叶黄素-CD-MCDS的特征在于体外溶出度测试，差示扫描比色法（DSC），傅立叶变换红外光谱（FT-IR），扫描电子显微镜（SEM）和粉末X射线衍射（PXRD）。此外，叶黄素-CD-MCDS在Caco-2细胞中的摄取明显高于游离叶黄素。与纯叶黄素相比，叶黄素-CD-MCDS的相对生物利用度增加到6.6倍，而与市售叶黄素软胶囊相比则增加到1.2倍。总之，开发了高溶解性叶黄素-CD-MCDS，其溶解度和生物利用度均得到了显着改善，并通过组合建模和实验方法进行了表征。我们的研究表明，计算机辅助配方设计是未来配方开发的一种有前途的方法。
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