School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.
Int J Pharm. 2022 Aug 25;624:122035. doi: 10.1016/j.ijpharm.2022.122035. Epub 2022 Jul 19.
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 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 solubilization 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.
在溶出试验中，通常会添加表面活性剂十二烷基硫酸钠（SLS）以增加难溶性药物的溶解并达到溶出槽条件。然而，本研究发现 0.1%的 SLS 会显著降低结晶盐酸鲁拉西酮（LH，一种 BCS Ⅱ类药物）的溶解率。本研究旨在阐明这一意外现象的机制，并探索减轻 SLS 对 LH 溶解的负面影响的策略。样品特性（如 PLM、DSC、PXRD、IR 和 NMR）证实，在 0.1%的 SLS 水溶液中溶解时，通过静电相互作用、四键相互作用和疏水作用形成了不溶性单相无定形 LH-SLS 复合物（在 35.2°C 处有单个 T）。由于水的增塑作用，无定形 LH-SLS 从玻璃态向粘性过冷液体态的转变导致凝胶形成，从而抑制了 LH 的溶解。同时，在各种浓度的 SLS 水溶液中 LH 的溶解度曲线呈现出异常的 V 形特征，SLS 的 CMC 值作为拐点，因为 SLS 的胶束增溶作用降低了凝胶程度。此外，基于潜在的竞争相互作用，开发了一种减轻 SLS 对 LH 溶解抑制作用的创新策略。本研究不仅丰富了表面活性剂抑制药物溶解的内在机制，还为减轻凝胶化提供了有效的策略。
