ABSTRACT

Background: Nowadays, the restriction and reduction of not environmentally friendly substances become one of the main considerations on raw materials development. Hence, organic solvent still often used to increase solubility. The safer compound is explored intensively to replace the conventional solubility enhancer. One of this is the use of Natural Deep Eutectic Solvents (NADES). L-proline (PRO) is an amino acid that has been reported can enhance the solubility and absorptivity of other compounds. Objective: This research attempted to combine PRO with the insoluble vitamins, namely tretinoin (TRET). Methods: The binary system between TRET-PRO was characterized by solid analysis instrumentation, such as thermal techniques (electrothermal and DSC) and non-thermal techniques (FTIR and PXRD). Furthermore, the eutectic mixture was collected through grinding which was aided by solvent dropping. This method is called solvent drop grinding (SDG). In addition, it was also done the recrystallization using ethanol. Furthermore, it was observed the solubility, diffusion, and stability of TRET after eutectic interaction with PRO. Results: The data revealed that this natural eutectic former decreased the melting point of TRET from 182°C to 147.6°C. The results of non-thermal analysis showed that no shift or new peak formation in the FTIR spectrum and PXRD diffractogram. The data reinforces the conclusion that the mixture is a eutectic system without producing a new phase. The results of solubility test show that PRO can increase solubility of TRET in water by 3.33 times. This mixture can also increase diffusion of TRET in pH 7.4 by 3.73 times. In addition, through the stability test it was proven that the eutectic mixture can increase stability of TRET against light, but absorb water faster than the environment compared to the single material. Conclusion: In conclusion, PRO functions as a NADES agent for TRET which can increase solubility, diffusion, and stability of TRET.

Key words: L-proline (PRO), tretinoin (TRET), eutectic, SDG, solubility, diffusion, stability