An environmentally benign HPLC-UV method for thermodynamic solubility measurement of vitamin D3 in various (Transcutol + water) mixtures

In the current research work, an environmentally benign “reversed phase high-performance liquid chromatography (RP-HPLC)” method was developed and validated for thermodynamic solubility measurement of vitamin D3 in various [2-(2-ethoxyethoxy)ethanol (Transcutol®) + water] mixtures. The HPLC analysis of vitamin D3 was achieved using a Nucleodur (150 × 4.6 mm, 5 μm) column. The binary mixture of ethanol: methanol (50:50% v/v) was used as a mobile phase and delivered at a flow rate of 1.0 mL min− 1. The proposed HPLC-UV method was validated well for linearity (R2 = 0.9997), selectivity, accuracy as % recovery (98.60-102.00%), precision (% RSD = 1.07-1.31), robustness and sensitivity. The potential of methodology was demonstrated by its application in thermodynamic solubility determination of vitamin D3 in different “Transcutol + water” mixtures at various temperatures. The “mole fraction solubilities (xe)” of vitamin D3 were measured at temperature “T = 273.2 K to 298.2 K” and pressure “p = 0.1 MPa”. Measured xe values of vitamin D3 were correlated well with “Apelblat, van't Hoff and Yalkowsky” models. The highest xe value of vitamin D3 was obtained in neat Transcutol (4.04 × 10− 1 at T = 298.2 K) followed by lowest one in neat water (1.97 × 10− 7 at T = 273.2 K). “Apparent thermodynamic analysis” of solubility values of vitamin D3 showed an “endothermic and entropy-driven dissolution” of vitamin D3. Overall, these results showed that the proposed HPLC-UV method could be successfully used for thermodynamic solubility determination of vitamin D3 in various “Transcutol + water” mixtures.