Temova Rakuša Žane, Pišlar Mitja, Kristl Albin, Roškar Robert
Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.
Pharmaceutics. 2021 Apr 25;13(5):617. doi: 10.3390/pharmaceutics13050617.
Vitamin D3 has numerous beneficial effects, such as musculoskeletal, immunomodulatory, and neuroprotective. However, its instability is the main obstacle to formulating quality products. Despite increased attention and growing use, data on vitamin D3 stability is scarce because data from individual studies is inconclusive and mostly qualitative. Therefore, we have systematically investigated the influence of various factors (temperature, light, oxygen, pH, concentration, and metal ions) on its stability in aqueous media using a stability-indicating HPLC-UV method. First-order kinetics fitted its degradation under all tested conditions except light and oxygen. In both cases, the established models in chemical kinetics were inappropriate and upgraded with the Weibull model. Metal ions and acidic conditions had the main destabilizing effect on vitamin D3 in aqueous media, but these solutions were successfully stabilized after the addition of ethylenediaminetetraacetic acid (EDTA), ascorbic acid, and citric acid, individually and in combination. EDTA showed the most significant stabilizing effect. Synergism among antioxidants was not observed. Our findings on vitamin D3 instability in aqueous media also correlated with its instability in commercial products. Vitamin D3 aqueous products require proper stabilization, thereby signifying the importance and contribution of the obtained results to the formulation of stable and quality products.
维生素D3具有多种有益作用,如对肌肉骨骼、免疫调节和神经保护等方面。然而,其不稳定性是制备高质量产品的主要障碍。尽管受到越来越多的关注且使用量不断增加,但关于维生素D3稳定性的数据却很匮乏,因为个别研究的数据尚无定论且大多为定性数据。因此,我们采用一种稳定性指示高效液相色谱 - 紫外检测法,系统地研究了各种因素(温度、光照、氧气、pH值、浓度和金属离子)对其在水性介质中稳定性的影响。除光照和氧气外,一级动力学适用于所有测试条件下其降解情况。在这两种情况下,化学动力学中已建立的模型并不适用,于是用韦布尔模型进行了升级。金属离子和酸性条件对水性介质中的维生素D3具有主要的 destabilizing 作用,但在分别或联合添加乙二胺四乙酸(EDTA)、抗坏血酸和柠檬酸后,这些溶液成功实现了稳定。EDTA显示出最显著的稳定作用。未观察到抗氧化剂之间的协同作用。我们关于维生素D3在水性介质中不稳定性的研究结果也与其在商业产品中的不稳定性相关。维生素D3水性产品需要适当的稳定化处理,从而表明所获结果对稳定且高质量产品配方的重要性和贡献。 (注:“destabilizing”直译为“破坏稳定的”,这里意译为“使不稳定的”更符合语境)