Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f₂ 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f₂ = 31.6); the optimal profile was obtained for Formula #4 (f₂ = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.

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评价新开发的含α-硫辛酸的固体口服速释配方的溶出度曲线

α-硫辛酸（ALA，硫辛酸）是一种天然存在的必需二硫醇化合物，已成为许多药物和食品补充产品（FSP）的常见成分，用于氧化应激相关的病理学；ALA的口服生物利用度受到药代动力学特性的限制，该特性会降低其治疗功效，降低的溶解度，缺乏胃稳定性和肝降解，并因配方障碍而加倍。目的是开发一种固体口服600 mg ALA FSP，与具有相似因子f ₂的参考上市药物（RLD）相比，可获得最佳的药物特性50.进行了比较溶出度研究；HPLC方法用于ALA定量。在计划了组合模拟（配方阶段）之后，制造了两个原型公式（＃1和＃2），并通过调整ALA物理特性和辅料数量（＃3和＃4）进行了进一步优化，以实现“质量目标产品配置文件”。对于＃3配方，观察到ALA体外释放的畸形（f ₂ = 31.6）；公式＃4（f ₂= 58.5）。简单的定量公式不足以确保良好的ALA生物利用度。该制剂需要在理化相容性算法下进行多种配混调节，并具有多种溶出度曲线来测试备用溶液。确保制剂具有与RLD相当的体外溶出度是至关重要的，即使对于食品补充剂制剂，也要使化合物达到其目标水平，以确保在细胞水平上ALA具有最佳的抗氧化活性。