期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 624, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2022.122035
关键词
Lurasidone hydrochloride; Sodium lauryl sulfate; Dissolution; Gelation
资金
- National Natural Science Foundation of China [81873012, 82074029, 82104401]
- Double First-Class University Project [CPU2018GY11, CPU2018GY27]
- Natural Science Foundation of Jiangsu Province [SBK2020042291]
- China Postdoctoral Science Foundation [2020M671665]
In this study, it was found that the addition of surfactant sodium lauryl sulfate (SLS) can increase the dissolution of insoluble drugs, but it significantly decreases the dissolution of crystalline lurasidone hydrochloride (LH). The insoluble single-phase amorphous LH-SLS complex formed during dissolution in 0.1% SLS aqueous solution, leading to gel formation and suppression of LH dissolution. An innovative strategy was developed to mitigate the inhibiting effect of SLS on LH dissolution based on potential competitive interactions.
In dissolution test, the surfactant sodium lauryl sulfate (SLS) is usually added to increase the dissolution of insoluble drugs and achieve the sink condition. However, the current study found that 0.1 % SLS would significantly decrease the dissolution of crystalline lurasidone hydrochloride (LH, a BCS II drug). The aim of this study was to clarify the mechanism of this unexpected phenomenon and explore a strategy for mitigating the negative effect of SLS on the dissolution of LH. Sample characterizations (such as PLM, DSC, PXRD, IR and NMR) confirmed that the insoluble single-phase amorphous LH-SLS complex (with a single T-g at 35.2 ?C) formed during dissolution in 0.1 % SLS aqueous solution via electrostatic interaction, tetrel bond interaction, and hydrophobic effect. Due to the plasticization effect of water, the transition of amorphous LH-SLS from its glassy state to viscous supercooled liquid state led to the gel formation, and suppressd the dissolution of LH. Meanwhile, the solubility curve of LH in SLS aqueous solution at various concentrations exhibited an unusual V-shaped feature, with the CMC value of SLS serving as the inflection point, since the gel degree was attenuated due to the micelle solu-bilization of SLS. Additionally, an innovative strategy was developed to alleviate the inhibiting effect of SLS on LH dissolution based on the potential competitive interactions. This study not only enriches the internal mechanism of surfactant-inhibited drug dissolution but also informs an effective strategy to mitigate the gelation.
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