Formulation and Characterization of a Ternary Inclusion Complex Containing Hydroxypropyl-β-cyclodextrin and Meglumine for Solubility Enhancement of Poorly Water-Soluble ST-246, an Anti-Smallpox Drug

作者：Li, Xiaoxi; Yang, Meiyan; Li, Yueqing; Gong, Wei; Wang, Yuli; Shan, Li; Shao, Shuai; Gao, Chunsheng^*; Zhong, Wu^*

来源：Current Drug Delivery, 2017, 14(8): 1130-1143.

DOI：10.2174/1567201813666161003151225

• Poorly water-soluble drug
• solubilization
• inclusion complex
• 2-hydroxypropyl-beta-cyclodextrin
• meglumine
• scanning electron microscope (SEM)

Background: The solubilization of poorly water-soluble drugs remains challenging. The purpose of this study was to design a liquid formulation that can improve the solubility of poorly water-soluble and weakly acidic ST-246, an anti-smallpox drug. @@@ Methods: Soluble ternary cyclodextrin complexations (t-CDs) containing ST-246, 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and meglumine (MEG) were prepared and optimized. The optimized t-CDs were further characterized using a scanning electron microscope (SEM), Powder X-ray Difffactometry (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance Spectroscopy (NMR). @@@ Results: The solubility of ST-246 improved dramatically from 3 mu g/ml (in water, 37 degrees C) to 50 mg/ml in the optimized t-CDs (ST-246/MEG/HP-beta-CD, 1:2:6 weight ratio). The results suggested that the drug was associated with MEG through hydrogen bonds and then included into the hydrophobic cavity of HP-beta-CD, which might be a major factor for solubility improvement. To determine the exact inclusion mechanism, a Phase Soluble Study (PSS) was also conducted, and it indicated that a 1:1 soluble complex was formed between ST-246 and HP-beta-CD and that the action mechanism of MEG was complicated and relied on more than pH modulation. @@@ Conclusion: Generally, the optimized ternarycyclodextrin complexation might be a potential formulation strategy for enhancing the solubility and bioavailability of poorly water-soluble ST-246.

• 出版日期2017
• 单位大连理工大学