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Progesterone Phospholipid Gel for Intramuscular Administration Prepared by In Situ-Phase Separation

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Abstract

Long-term daily injection of progesterone for the treatment of threatened abortion can be a source of considerable pain to patients. To reduce the frequency of injections and improve patient compliance, a novel injectable phospholipid-based phase separation gel (PPSG) was prepared using small molecular materials such as phospholipids, medium-chain triglycerides (MCTs), and ethanol. Progesterone was loaded into PPSGs to promote rapid gel formation in situ via a sol-gel transformation mechanism, thereby achieving a sustained controlled release. Furthermore, progesterone was distributed in the oil-water interface layer and within the oil phase. Solvent exchange drives phase transitions, and phospholipid vesicle formation and rupture are likely to promote drug release and gel degradation. At a drug loading of 140 mg/mL, a progesterone release of up to 60% could be reached within 9 days according to the release curve in vitro. Pharmacokinetic studies demonstrated that the progesterone-loaded PPSGs released the drug continuously for over 7 days, the half-life was eight times higher than that of progesterone oil solution, and relative bioavailability of up to 184.90% was obtained. Collectively, the sustained release properties for hydrophobic cargos would effectively enhance patient compliance. Moreover, PPSGs are promising drug delivery systems that have high market value and biosafety given the readily accessible and safe excipients.

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Funding

This work was supported by the National Key R&D Program of China (No. 2020YFE0201700), Liaoning Revitalization Talents Program (No. XLYC1908031), and National Mega-project for Innovative Drugs (No. 2019ZX09721001).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Ning Dong, Lihua Tang, Meihui Zhao, Yingchao Zhang, Yu Zhang, Haibing He, Jingxin Gou, Yue Yuan & Xing Tang

  2. School of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Tian Yin

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  1. Ning Dong
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Contributions

Ning Dong: acquisition, analysis, interpretation, and drafting the work; Lihua Tang: acquisition, analysis, and interpretation; Meihui Zhao: acquisition, analysis; Yingchao Zhang: acquisition, analysis; Yu Zhang: analysis, interpretation; Tian Yin: analysis, interpretation; Haibing He: analysis, interpretation; Jingxin Gou: analysis, interpretation; Yue Yuan: design of the work, analysis, interpretation, and drafting the work. Xing Tang: design of the work, analysis, interpretation, and drafting the work.

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Dong, N., Tang, L., Zhao, M. et al. Progesterone Phospholipid Gel for Intramuscular Administration Prepared by In Situ-Phase Separation. AAPS PharmSciTech 23, 294 (2022). https://doi.org/10.1208/s12249-022-02442-2

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