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Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride

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Abstract

The purpose of this work is to explore the effects of novel absorption enhancers on the nasal absorption of nalmefene hydrochloride (NMF). First, the influence of absorption enhancers with different concentrations and types and drug concentrations on the nasal absorption of NMF was investigated in vivo in rats. The absorption enhancers studied include n-dodecyl-β-d-maltoside (DDM), hydroxypropyl-β-cyclodextrin (HP-β-CD), and polyethylene glycol (15)-hydroxy Stearate (Solutol®HS15). At the same time, the in situ toad palate model and rat nasal mucosa model were used to assess the cilia toxicity. The results showed that all the absorption enhancers investigated significantly promote the nasal absorption of NMF, but with different degrees and trends. Among them, the 0.5% (w/v) DDM had the strongest enhancement effect, followed by 0.5% (w/v) Solutol®HS15, 0.25% (w/v) DDM, 0.25% (w/v) Solutol®HS15, 0.1% (w/v) Solutol®HS15, 0.1% (w/v) DDM, and 0.25% (w/v) HP-β-CD, with absolute bioavailability of 76.49%, 72.14%, 71.00%, 69.46%, 60.41%, 59.42%, and 55.18%, respectively. All absorption enhancers exhibited good safety profiles in nasal ciliary toxicity tests. From the perspective of enhancing effect and safety, we considered DDM to be a promising nasal absorption enhancer. And in addition to DDM, Solutol®HS15 can also promote intranasal absorption of NMF, which will provide another option for the development of nalmefene hydrochloride nasal spray.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number 82073793) and the National Key Technologies Research and Development Program for New Drugs of China (grant number 2018ZX09721003-007).

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Authors and Affiliations

  1. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Ting Zhang & Guangjun Nie

  2. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100850, China

    Ting Zhang, Meng Li, Xiaolu Han & Aiping Zheng

  3. Beijing Institute of Pharmacology and Toxicology, Academy of Military Sciences, Haidian District, 27th Taiping Road, Beijing, 100850, People’s Republic of China

    Aiping Zheng

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  1. Ting Zhang
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  2. Meng Li
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  3. Xiaolu Han
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Contributions

All authors contributed to this study conception and design. Material preparation and data collection and analysis were performed by Guangjun Nie, Aiping Zheng, Ting Zhang, Meng Li, and Xiaolu Han. The first draft of the manuscript was written by Ting Zhang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Aiping Zheng.

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Zhang, T., Li, M., Han, X. et al. Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride. AAPS PharmSciTech 23, 143 (2022). https://doi.org/10.1208/s12249-022-02252-6

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  • DOI: https://doi.org/10.1208/s12249-022-02252-6

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