Solubilization of poorly water-soluble drugs through partition/association equilibrium: Thermodynamic insights using...

This study investigates the thermodynamics of solubilizing poorly water-soluble drugs using a biodendrimeric solid dispersion (BDSD) platform consisting of an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) and poloxamer 338 (PLX). Three model drugs were selected: phenytoin (PHT), griseofulvin (GSF), and ibuprofen (IBU). Isothermal titration calorimetry (ITC), an effective method for characterizing thermodynamic parameters of intermolecular interactions, was utilized. The findings revealed that solubilization of these drugs by OS-DLB is thermodynamically favorable. For IBU, the most hydrophobic model drug, the numerous weak interactions between the solutes and OS-DLB produce an enthalpic effect sufficient to counteract the strong attractive forces among water molecules, significantly enhancing the apparent solubility of IBU. For the semipolar model drugs, PHT and GSF, the interactions between the solutes and the hydrocarbon chains are not sufficient to overcome the hydrogen bonds between water molecules, resulting in minimal to moderate solubility enhancement. The presence of PLX in the formulation was found to influence the solubilizing power of OS-DLB, depending on the compatibility between the PLX-modified OS-DLB microenvironment and the hydrophobicity of the drug. The intrinsic polarity of IBU closely matches that within OS-DLB; consequently, PLX plays only a moderate role in enhancing the solubilizing capacity of OS-DLB. For PHT, the least hydrophobic model drug, the polarity shift within OS-DLB facilitated by PLX is insufficient to effect a significant solubility enhancement. The maximum potentiation effect of PLX is observed with GSF, the model drug with intermediate hydrophobicity. This effect is attributable to the increased interactions between the solutes and the hydrocarbon chains, resulting in greater enthalpic and entropic contributions.