Phase behavior of concentrated hydroxypropyl methylcellulose solution in the presence of mono and divalent salt

Abstract

Thermo reversible sol–gel transitions of hydroxypropylmethylcellulose (HPMC) are critical for many pharmaceutical, cosmetic, and food applications. This study examined the effects of salt (NaCl and CaCl₂) on the viscoelastic properties of concentrated low molecular weight HPMC solutions and found that the gelation temperature decreased linearly as a function of salt concentrations, independent of valency of cations and the mole concentration of anions. Thermal analysis showed that the depression of melting temperature can be fitted for both NaCl and CaCl₂ as a function of the total number of ions by a single linear curve, which was consistent with the melting point depression of pure water by NaCl and CaCl₂, but with a higher linear slope.

Introduction

Hydroxypropylmethylcellulose (HPMC) (or hypromellose) is a non-ionic, linear polysaccharide that is obtained by modifying the hydroxyl position in cellulose. HPMC has been used in many applications such as thickeners, binders, and film-forming agents in the pharmaceutical, food, cosmetics, and ceramic processing industries (Clasen and Kulicke, 2001, Ford, 1999). Salts are commonly present in many of the formulations used.The rheological characteristics of the hypromellose solutions in the presence of salts is therefore crucial in designing the formulation and manufacturing process for these applications.

It is well known that HPMC can undergo thermo reversible sol–gel transition. Thermogelation of HPMC and other cellulose derivatives have previously been studied using rheology (Bajwa et al., 2009, Haque and Morris, 1993, Hussaina et al., 2002, Kobayashi et al., 1993, Li et al., 2002, Silva et al., 2008), NMR (Haque, Richardson, Morris, Gidley, & Caswell, 1993), FTIR (Bajwa et al., 2009), dynamic light scattering (Kobayashi et al., 1993), small angle neutron scattering (Kobayashi et al., 1993), and DSC (Ford, 1999, Lam et al., 2007, Li et al., 2002). It has also been shown that the gelation mechanism of HPMC is a two stage process (Carlssona et al., 1990, Ibbett et al., 1992, Kobayashi et al., 1993), where the first stage occurs at low tempratures with association of HPMC or MC polymers and the second stage occurs at higher temperatures with a phase separated system. Recent studies using Cryo-TEM and other techniques have shown that HPMC gelation occurs due to aggregation and network structure formation (Bodvika et al., 2010).

The effect of salt on thermo gelation of HPMC has been previously studied using DSC and rheology measurements (Liu et al., 2008a, Xu et al., 2004a, Xu et al., 2004b). The gelation temperature of HPMC was increased or decreased by addition of salts where the degree of increase/decrease followed Hofmeister series (Liu et al., 2008a, Mitchell et al., 1990, Xu et al., 2004a, Xu et al., 2004b). More specifically, the thermo gelation temperature of HPMC in the presence of anions increased following the order of SCN⁻ > ClO₄^_ > I⁻ with SCN⁻ having the greatest increase, and decreased following the order of NO₃⁻ ≈ Br⁻ < Cl⁻ < F⁻ < H₂PO₄ ⁻ < S₂O₃²⁻ < SO₄²⁻ with SO₄²⁻ having the most depression on gelation temperature. The gelation temperature of other amphiphilic polymers in the presence of cations decreased in the following order: Na⁺ > K⁺ > Li⁺, with the Na⁺ having the greatest effect, however the effect of cations is less significant than that of anions (Alexandridis & Holzwarth, 1997). Additionally, it was found that the amount of depression of the gelation temperature increased with increasing salt concentrations (Alexandridis and Holzwarth, 1997, Mitchell et al., 1990, Xu et al., 2006, Xu et al., 2004a, Xu et al., 2004b).

The main objective of this study was to examine the effects of salt on the viscoelastic properties of concentrated low molecular weight HPMC solutions, as previous research mainly focused on high molecular weight HPMC and low concentration HPMC solutions (Liu et al., 2008a, Liu et al., 2008b, Silva et al., 2008, Xu et al., 2006). Both the rheological and thermal properties of a hypromellose solution with and without salts were investigated. NaCl and CaCl₂ were selected as model monovalent and divalent salts, respectively.