TY - JOUR
T1 - Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride
AU - Zhang, Ting
AU - Li, Meng
AU - Han, Xiaolu
AU - Nie, Guangjun
AU - Zheng, Aiping
N1 - Funding Information:
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).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - DDM
KW - HP-β-CD
KW - Solutol®HS15
KW - absorption enhancer
KW - nalmefene hydrochloride
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U2 - 10.1208/s12249-022-02252-6
DO - 10.1208/s12249-022-02252-6
M3 - Article
C2 - 35578146
AN - SCOPUS:85130042054
VL - 23
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
SN - 1530-9932
IS - 5
M1 - 143
ER -