Effects of salts in the Hofmeister series and solvent isotopes on the gelation mechanisms for hydroxypropylmethylcellulose hydrogels

Abstract

The effects of various inorganic salts and isotopic solvents on the thermal gelation behavior of hydroxypropylmethylcellulose (HPMC) in aqueous solutions were examined by micro-differential scanning calorimetry and rheological measurements. It was found that salting-out salts, such as NaCl, promoted the sol-gel transition of HPMC at a lower temperature. An analysis of solvent isotope effects on the changes in the temperature at maximum heat capacity (T m ) with salt concentration showed that interchain hydrogen bonding (hydrogen bonding between the hydroxyl groups of different HPMC chains) was involved in the sol-gel transition, and its strength depended on the temperature and salt concentration. It was demonstrated that the effectiveness of anionic species in changing the T m of the HPMC solutions was in the sequence of the Hofmeister series. Anionic species play a role in reducing T m by their influence on the structure of the water, which in turn affects interactions between hydroxyl groups and water molecules, interchain hydrogen bonding, and the strength of the water cages prohibiting hydrophobic association. Rheological and microcalorimetric results indicated that the change in the thermodynamics of gelation of the HPMC aqueous solution was determined by the salt types and concentration, and the effect of monovalent salts was found to be more cooperative than that of multivalent salts on the sol-gel transition.

The Properties of HPMC:PEO Extended Release Hydrophilic Matrices and their Response to Ionic Environments

“…In the presence of up to 0.4M NaCl, matrices containing HPMC and 8:2 HPMC:PEO, show increased T80 values, but at 0.8M these matrices exhibit a marked acceleration of drug release. This effect has been previously reported in other HPMC matrix formulations [9] and has been attributed to the failure of an effective gel layer diffusion barrier, during the early stages of matrix hydration, as a result of inhibition of polymer swelling through Hofmeister effects [35,36].…”

“…PEO hydration is reported to be sensitive to salts [35][36][37][38], but in these investigations the threshold concentration was clearly much higher for PEO than for HPMC.…”

Designing HPMC matrices with improved resistance to dissolved sugar

“…Imaging studies suggested this behaviour arose from sugar-induced suppression of polymer hydration and a subsequent loss of gel layer diffusion-barrier function (Williams et al, 2009). The threshold concentration, S CRIT varied between sugars, and correlated with their ability to disrupt water structure and to suppress the polymer sol:gel transition temperature in a manner analogous to the Hofmeister effects seen with inorganic salts (Alderman, 1984;Liu et al, 2008;Pygall et al, 2009). The concentrations of sugar required to achieve S CRIT (0.5 M-1.15 M) were commonly higher than concentrations found in foods, and were considered unlikely to be encountered in the fed stomach.…”

Solution interactions of diclofenac sodium and meclofenamic acid sodium with hydroxypropyl methylcellulose (HPMC)

“…The mechanism is considered to involve the re-orientation of water molecules around regions of hydrophobic substitution, and the formation of an insoluble three-dimensional polymer gel network through hydrophobic interactions (Sarkar 1979;Haque and Morris, 1993). More recent advances in our understanding of Hofmeister effects has suggested that ions can directly interact with the hydration sheath of macromolecules (Zhang and Cremer, 2006) and this can be applied to the many historical studies of 'saltingin' and 'salting-out' of HPMC by electrolyte solutions (Touitou and Donbrow, 1982;Mitchell et al, 1990;Kajiyama et al, 2008;Liu et al, 2008).…”