Investigation on Hansen Solubility Parameter of Caffeine Dissolved in Different Pure Solvents

Aims: Solubility is a molecular property decisive in the entire process from drug development and design to the final drug formulation and production, the main objective of this paper is to explain the effect of the variance in molecular properties and intermolecular interaction on dissolution by Hansen Solubility Parameter (HSP) and KAT-LSER model.

Study Design: Solubility is a molecular property decisive in the entire process from the drug development and design to the final drug formulation and production, the main objective of this paper is to explain the effect of the variance in molecular properties and intermolecular interaction on dissolution by Hansen Solubility Parameter (HSP) and KAT-LSER model.

Place and Duration of Study: Department of Biomedical Sciences, Faculty of Pharmacy. Between April 2023-April 2024.

Methodology: The solubility of the drug was measured in pure mono solvents of several chemical classes keys in formulation, purification, and crystal formation of drugs. HSP was tested to determine the partial solubility parameters of caffeine. The logarithm of the mole fraction experimental solubility ln X2 as the dependent variable was used. KAT-LSER model was used to show that solute-solvent interactions are principally attributed to the dipolarity/polarizability interaction and the hydrogen bonding basicity. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT‐IR) were performed for the original powder and the solid phase after equilibration with the pure solvents.

Results: Good results were obtained with the model of three- and four-partial parameters of solubility. Since the dispersion parameter does not greatly vary from one drug to another, the variation of solubility among solvents is largely due to the dipolar and hydrogen bonding parameters, a fact that is consistently found for other drugs of small molecular weight. DSC and FT-IR allow the detection of possible changes in the thermal properties of the solid phase and verify the anhydrous nature of the starting material.

Conclusion: The results showed that the solubility of caffeine is mostly affected by polarity and/or hydrogen bonding.