表面活性剂对无定形固体分散体的溶液行为和膜传输的影响

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Amjad Alhalaweh, Mira El Sayed, Lucia Kovac, Christel A S Bergström
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引用次数: 0

摘要

本研究的目的是开发一种难溶性化合物(AK100)的无定形固体分散体(ASD),并研究不同表面活性剂对其溶解、过饱和及膜传输的影响。在没有和有三种不同浓度的表面活性剂(十二烷基硫酸钠(SDS)、聚山梨醇酯 80(PS80)和 D-α-生育酚聚乙二醇琥珀酸酯(TPGS))的情况下,测定了 AK100 的晶体和无定形溶解度。利用计算模型评估了溶解度与表面活性剂溶解度之间的关系。通过溶剂蒸发法制备了 ASD 粉末,进行了含有和不含预溶解表面活性剂的非沉降溶解实验。用 Caco-2 细胞进行了运输研究,以评估基于表面活性剂的配方对膜运输的影响。随着表面活性剂浓度的增加,AK100 的相应结晶溶解度和无定形溶解度均呈线性增加。在无表面活性剂和有 TPGS 的情况下,过饱和度至少能维持三小时,而在有 SDS 和 PS80 的情况下,过饱和度会下降。正如预期的那样,ASD 的 AK100 膜通量高于结晶粉末,并且随着 TPGS 浓度的增加而进一步提高。对于无定形和结晶形式的 AK100,根据 Caco-2 细胞研究中基于活性的计算得出的过饱和度比始终高于基于浓度的计算得出的过饱和度比。这项研究表明,在制剂开发过程中添加增溶辅料可以改善过饱和药物溶液的溶解和相行为。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of Surfactants on Solution Behavior and Membrane Transport of Amorphous Solid Dispersions.

The purpose of the study was to develop an amorphous solid dispersion (ASD) of a poorly soluble compound (AK100) and investigate the impact of different surfactants on its dissolution, supersaturation and membrane transport. The solubility of the AK100 was determined in crystalline and amorphous form in the absence and presence of three surfactants at different concentrations: sodium dodecyl sulphate (SDS), polysorbate 80 (PS80) and D-α-tocopherol polyethylene glycol succinate (TPGS). The relation between solubility and surfactant solubilization was evaluated using a computational model. The ASD powder was prepared by solvent evaporation for non-sink dissolution experiments with and without the pre-dissolved surfactants. A transport study with Caco-2 cells was conducted to evaluate the impact of surfactants-based formulation on membrane transport. Both the corresponding crystalline and amorphous solubility of AK100 increased linearly as a function of the surfactant concentrations. The supersaturation was maintained for at least three hours in absence of surfactant and in presence of TPGS, whereas supersaturation declined with SDS and PS80. As expected, the membrane flux of the AK100 was higher for the ASD than for the crystalline powder, and further increased with increased concentration of TPGS. The supersaturation ratio based on the activity-based calculation from Caco-2 cells study was always higher than that of the concentration-based one for the amorphous and crystalline forms of AK100. This study shows how additional solubilizing excipients during formulation development can improve the resulting dissolution and phase behavior of supersaturated drug solution.

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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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