Novel insight in thermo-oxidative kinetics of vitamin D-based supplement formulation using TG–DTG–DTA, ATR-FTIR and MALDI-MS techniques

This work provides detailed mechanistic analysis of thermo-oxidative degradation behavior of vitamin D3—Ca (CaCO 3 form) solid state supplement formulation. Analytical techniques such Attenuated Total Reflection Fourier-transform Infrared (ATR-FTIR) spectroscopy and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) were used for analysis of homogeneity of active pharmaceutical ingredients (APIs) throughout excipients contained within solid dosage forms. Information gained from MALDI-MS experiments was used to improve and better understand interactions present, later clearly disclosed through kinetic modeling. It was found that process mechanism proceeds via two single-step unbranched reactions and two steps of consecutive reactions. Key features include vitamin D3 meltings and degradation via hydrogen abstraction followed by addition of oxygen forming 1-hydroxy-vitamin D3 and further through its dehydration to 1-keto-vitamin D3. Identified product 1-hydroxy-vitamin D3 is substantial for enhancing the immune response of human body in fight against respiratory viruses. Another two degradation products, namely pyrocalciferol and isopyrocalciferol, produced by thermal isomerization at higher temperatures, were also identified. These vitamin epimers have crucial role in functioning of immune cells. Degradation process of mineral structure occurs through water molecules removal, forming anhydrous polymorph of CaCO 3 , where formation of solid (CaO) and gaseous (CO 2 ) products participates in kinetically stabilized additive-functionalized amorphous CaCO 3 crystallization. Confirmation of correctness of proposed degradation mechanism was verified by modulated dynamic (MD) predictions. Information obtained is valuable and suitable for safety evaluations of given supplement, but also could be applied for solid state forms, which are generally sensitive to oxidative conditions.