Investigation of the interaction between curcumin and hydroxypropyl methylcellulose acetate succinate in solid and solution media

Abstract

Solubility and bioavailability are the main factors that affect the use of drugs and active ingredients, including curcumin (CUR). Among the ways to improve the properties of CUR are the polymeric matrices. This work aims to investigate the solubilization of CUR in the presence of macromolecular hydroxypropyl methyl cellulose succinate acetate (HPMCAS). Through the group contribution method, the compatibility between CUR and HPMCAS, which presented similar solubility components (Δδt < 7 MPa1/2), was analyzed. DSC measurements showed a depression of the CUR melting point in the presence of HPMCAS. The calculated Flory-Huggins parameter (−2.057 ± 0.25) indicates compatibility between the polymer and the CUR. The degree of crystallinity (Xc) of the CUR in the solid state (by XRPD) and in the molten state (by DSC) was calculated, noting that in the solid state the Xc was significantly higher. The intrinsic solubility of CUR in HPMCAS ranged from 102.84 to 62.40 when the temperature was raised from 293 K to 313 K with an enthalpy change of −18.01 ± 2.34 kJ mol−1 and entropy of 80. 9 ± 7.8 J mol−1 K−1. This process had a Gibbs free energy change with temperature variation of about −1.56 kJ mol−1 due to the solubilization of CUR in the internal hydrophobic core of HPMCAS. Particle sizes were detected indicating two populations of particles. The first (31.1 to 86 nm) and second (0.23 to 6.6 μm) populations were classified as unstable (< ±20 mV) by zeta potential (ζ). These results indicate that HPMCAS reorganization in the presence of CUR promotes a hydrophobic core capable of stabilizing CUR in solution. The formation of colloidal nanoparticles was confirmed by TEM which exhibited an effective diameter of 92 to 353 nm. As verified by ζ, colloidal instability was confirmed after 48 h, after which there was no change in the solubility of CUR in the system, showing that HPMCAS promotes a metastable state. The solubilization process and the formation of colloidal aggregates indicate how the drug dispersion process in the matrix can help in the production of pharmaceutical formulas.