Construction of thermodynamic phase diagrams for luteolin – povidone binary solid mixtures

Luteolin (LUT) is a bioflavonoid that possesses several formulation-related problems due to its poor aqueous solubility [1]. This limitation may be resolved by formulating the API in its amorphous form. In this context, the aim of the present study is the thermophysical characterization of amorphous LUT and its binary mixtures with povidone (PVP), in order to determine the critical formulation parameters (e.g., recrystallization and/or phase transition regions) for the preparation of LUT amorphous drug formulations. In this vein, phase transition diagrams (i.e., temperature vs. concentration plots) of the active substance with PVP were constructed using differential scanning calorimetry (DSC) and the Flory-Huggins (FH) lattice theory, through which the dispersion of the pharmaceutical substance in the polymer behaves exactly like a polymer solution, with the difference that the API itself is in the place of the solvent. Fitting of the FH equation in the experimentally (DSC) determined drug melting temperatures at various LUT/PVP ratios, revealed a negative FH interaction parameter (χ) indicating that the API is thermodynamically miscible with the said polymer. Additionally, it was found that at 25 °C, which is a common storage temperature for pharmaceutical products, the “metastable” zone of the mixture (i.e., the zone between liquidus and spinodal) extends at concentrations below 10% w/w of the active substance, indicating that in ASDs having higher API quantities drug-polymer amorphous-amorphous phase separation is favored.

• Reference

• 1 Liu J, Sun Y, Cheng M. et al. Improving oral bioavailability of luteolin nanocrystals by surface modification of sodium dodecyl sulfate. AAPS PharmSciTech 2021; 22 (03) 133

Publication History

Article published online:
12 December 2022