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Phytantriol-Based In Situ Liquid Crystals with Long-Term Release for Intra-articular Administration

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Abstract

The purpose of this study was to develop an injectable in situ liquid crystal formulation for intra-articular (IA) administration, and in situ forming a viscous liquid crystalline gel with long-term release of sinomenine hydrochloride (SMH) upon water absorption. The pseudo-ternary phase diagram of phytantriol (PT)-ethanol (ET)-water was constructed, and isotropic solutions were chosen for further optimization. The physicochemical properties of isotropic solutions were evaluated, and the phase structures of liquid crystalline gels formed by isotropic solutions in excess water were confirmed by crossed polarized light microscopy (CPLM) and small-angle X-ray scattering (SAXS). In vitro drug release studies were conducted by using a dialysis membrane diffusion method. The optimal in situ cubic liquid crystal (ISV2) (PT/ET/water, 64:16:20, w/w/w) loaded with 6 mg/g of SMH showed a suitable pH, showed to be injectable, and formed a cubic liquid crystalline gel in situ with minimum water absorption within the shortest time. The optimal ISV2 was able to sustain the drug release for 6 days. An in situ hexagonal liquid crystal (ISH2) system was prepared by addition of 5% vitamin E acetate (VitEA) into PT in the optimal ISV2 system to improve the sustained release of SMH. This ISH2 (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w) was an injectable isotropic solution with a suitable pH range. The developed ISH2 was found to be able to sustain the drug release for more than 10 days and was suitable for IA injection for the treatment of rheumatoid arthritis (RA).

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ACKNOWLEDGMENTS

The authors are supported by National Natural Science Foundation of China (No. 81274099), Anhui Provincial Natural Science Foundation (No. 1408085QH183), Anhui Provincial Natural Science Foundation (No. 11040606 M219), Natural Science Foundation of the Anhui Higher Education Institutions of China (No. KJ2012A184), and Anhui Provincial Training Plan for a Thousand of Talents. The content is solely the responsibility of the authors and does not necessarily represent the official views of Anhui University of Chinese Medicine or Hospira Inc.

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The authors declare that there is no conflict of interests regarding the publication of this article.

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Correspondence to Shuangying Gui.

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Chen, Y., Liang, X., Ma, P. et al. Phytantriol-Based In Situ Liquid Crystals with Long-Term Release for Intra-articular Administration. AAPS PharmSciTech 16, 846–854 (2015). https://doi.org/10.1208/s12249-014-0277-6

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