Dolinina Ekaterina S, Akimsheva Elizaveta Yu, Parfenyuk Elena V
G. A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 153045 Ivanovo, Russia.
Pharmaceutics. 2020 Mar 4;12(3):228. doi: 10.3390/pharmaceutics12030228.
Powerful antioxidant α-lipoic acid (LA) is easily degraded under light and heating. This creates difficulties in its manufacture, storage and reduces efficiency and safety of the drug. The purpose of this work was to synthesize novel silica-based composites of LA and evaluate their ability to increase photo and thermal stability of the drug. It was assumed that the drug stabilization can be achieved due to LA-silica interactions. Therefore, the composites of LA with unmodified and organomodified silica matrixes were synthesized by sol-gel method at the synthesis pH below or above the pKa of the drug. The effects of silica matrix modification and the synthesis pH on the LA-silica interactions and kinetics of photo and thermal degradation of LA in the composites were studied. The nature of the interactions was revealed by FTIR spectroscopy. It was found that the rate of thermal degradation of the drug in the composites was significantly lower compared to free LA and mainly determined by the LA-silica interactions. However, photodegradation of LA in the composites under UV irradiation was either close to that for free drug or significantly more rapid. It was shown that kinetics of photodegradation was independent of the interactions and likely determined by physical properties of surface of the composite particles (porosity and reflectivity). The most promising composites for further development of novel silica-based formulations were identified.
强效抗氧化剂α-硫辛酸（LA）在光照和加热条件下容易降解。这给其生产、储存带来困难，并降低了药物的有效性和安全性。本研究的目的是合成新型的LA二氧化硅基复合材料，并评估它们提高药物光稳定性和热稳定性的能力。假定药物的稳定化可通过LA与二氧化硅的相互作用来实现。因此，通过溶胶-凝胶法在药物pKa以下或以上的合成pH值条件下，合成了LA与未改性和有机改性二氧化硅基质的复合材料。研究了二氧化硅基质改性和合成pH值对复合材料中LA与二氧化硅相互作用以及LA光降解和热降解动力学的影响。通过傅里叶变换红外光谱（FTIR）揭示了相互作用的本质。结果发现，与游离LA相比，复合材料中药物的热降解速率显著降低，且主要由LA与二氧化硅的相互作用决定。然而，复合材料在紫外线照射下的LA光降解要么与游离药物相近，要么显著更快。结果表明，光降解动力学与相互作用无关，可能由复合颗粒表面的物理性质（孔隙率和反射率）决定。确定了最有前景的复合材料，用于进一步开发新型二氧化硅基制剂。
