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

Title: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

Volume: 14 Issue: 8

Author(s): Xiaoxi Li, Meiyan Yang, Yueqing Li, Wei Gong, Yuli Wang, Li Shan, Shuai Shao, Chunsheng Gao*Wu zhong*

Affiliation:

• State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850,China

• State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850,China

Keywords: Poorly water-soluble drug, solubilization, inclusion complex, 2-hydroxypropyl-β-cyclodextrin, meglumine, scanning electron microscope (SEM).

Abstract: 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-β- cyclodextrin (HP-β-CD) and meglumine (MEG) were prepared and optimized. The optimized t-CDs were further characterized using a scanning electron microscope (SEM), Powder X-ray Diffractometry (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 µg/ml (in water, 37°C) to 50 mg/ml in the optimized t-CDs (ST-246/MEG/HP-β-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-β-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-β-CD and that the action mechanism of MEG was complicated and relied on more than pH modulation.

Conclusion: Generally, the optimized ternary cyclodextrin complexation might be a potential formulation strategy for enhancing the solubility and bioavailability of poorly water-soluble ST-246.

Cite this article as:

Li Xiaoxi, Yang Meiyan, Li Yueqing, Gong Wei, Wang Yuli, Shan Li, Shao Shuai, Gao Chunsheng*, zhong Wu*, 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, Current Drug Delivery 2017; 14 (8) . https://dx.doi.org/10.2174/1567201813666161003151225