Purpose

The study aims to explore the potential of amorphous solid dispersion (ASD) technology in improving the solubility and bioavailability of flutamide (FLT), a poorly water-soluble drug. The introduction of beta-cyclodextrin (β-CD) is investigated as a strategy to overcome FLT’s solubility limitations.

Methods

The study employed various methods, including a validated UV spectrophotometric technique to assess FLT solubility and the creation of supersaturation through different β-CD and FLT combinations. Two formulation approaches, physical mixtures (PMs) and solid dispersions (SDs), were developed using freeze-drying and solvent evaporation methods. Analysis involved differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), along with loading and release tests, including statistical analysis of dissolution profiles.

Results

The FTIR analysis indicated that molecular interactions and chemical bonds remained largely unchanged. DSC results demonstrated the transformation of FLT from a crystalline to an amorphous state in the SDs. In the supersaturation test, it was evident that the solution with 30% β-CD and 70% FLT achieved a remarkable 5.69-fold increase in FLT concentration compared to the pure drug. Solid dispersion formulations exhibited varying drug release profiles, with the 30% β-CD and 70% FLT combination showing the most rapid release, reaching approximately 50% within 240 min.

Conclusion

The study underscores the effectiveness of β-CD in the 30:70 β-CD to FLT combination to enhance FLT solubility and bioavailability. However, higher proportions of β-CD led to reduced drug release, potentially due to cyclodextrin aggregation, which could hinder drug interactions.

Graphical Abstract

中文翻译：

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使用 β-环糊精通过过饱和增强氟他胺的溶出：一种改善水溶性差的药物溶解度的有前景的方法

目的

该研究旨在探索无定形固体分散体（ASD）技术在提高难溶性药物氟他胺（FLT）的溶解度和生物利用度方面的潜力。研究人员研究了引入 β-环糊精 (β-CD) 作为克服 FLT 溶解度限制的策略。

方法

该研究采用了多种方法，包括经过验证的紫外分光光度技术来评估 FLT 溶解度，以及通过不同的 β-CD 和 FLT 组合产生过饱和度。使用冷冻干燥和溶剂蒸发方法开发了两种配方方法：物理混合物（PM）和固体分散体（SD）。分析涉及差示扫描量热法 (DSC) 和傅里叶变换红外光谱 (FTIR)，以及加载和释放测试，包括溶出曲线的统计分析。

结果

FTIR 分析表明分子相互作用和化学键基本保持不变。DSC 结果表明，SD 中 FLT 从结晶态转变为非晶态。在过饱和测试中，很明显，与纯药物相比，含有30％β-CD和70％FLT的溶液的FLT浓度显着增加了5.69倍。固体分散体制剂表现出不同的药物释放曲线，其中 30% β-CD 和 70% FLT 组合显示出最快的释放速度，在 240 分钟内达到约 50%。

结论

该研究强调了 β-CD 以 30:70 的 β-CD 与 FLT 组合的形式有效提高了 FLT 的溶解度和生物利用度。然而，较高比例的 β-CD 会导致药物释放减少，这可能是由于环糊精聚集造成的，这可能会阻碍药物相互作用。

图形概要