Rheological and Stability Evaluation of Sodium Alginate as a Pharmaceutical Excipient Under Varying pH

The following poster was presented at IPEC Americas Excipient World 2025:

PURPOSE

Sodium alginate, a naturally occurring polysaccharide, serves as a widely utilized pharmaceutical excipient owing to its biocompatibility, biodegradability, non-toxicity, gelling attributes, and capacity to form gels in the presence of calcium ions (ionotropic gelation)1. Structurally, sodium alginate can be delineated as an anionic copolymer, consisting of mannuronic acid (M block) and guluronic acid (G block) units organized in a non-uniform block wise configuration with diverse ratios of GG, MG, and MM blocks2. Its applications span various domains, including drug delivery systems, wound dressings, and functioning as a binder or diluent in tablet formulations3. Sodium alginate constitutes a polysaccharide characterized by its hydrophilic attributes, and its aqueous dispersions exhibit colloidal characteristics4. It is soluble in both cold and hot aqueous environments. The molecular weight of sodium alginate varies between 12,000 and 400,000 Daltons5. Notwithstanding its extensive application, there exists a paucity of comparative data regarding the influence of source variability and pH fluctuations on the rheological performance of sodium alginate within pharmaceutical settings. Furthermore, the long-term stability of alginate-based formulations under varying storage conditions remains an under investigated domain, especially concerning viscosity evolution.

OBJECTIVES

The objective of this study was to elucidate the influence of pH on the viscosity of sodium alginate. Thus, This study presents a comprehensive rheological analysis of sodium alginate from various sources under different pH conditions relevant to pharmaceutical applications. Further objectives was to investigate the stability of sodium alginate solutions from a singular source subjected to varying pH levels while maintained under refrigeration (2–8 °C) and regular conditions (25 °C/60% RH) over a duration of six months.

METHODS

In this study, we studied the pH-dependent viscosity change behavior of four different grades of sodium alginate from two different sources, namely, Pronova UP MVG (IFF N&H Norway AS) and VIVAPHARM® Alginate PHU 175, 173 and 152 Samples (JRS PHARMA France) designated as JRS-1, JRS-2 and JRS-3 respectively (see Table 1). In a typical experiment, Na alginate 1.2% w/v was dissolved in deionized water (DW) using a magnetic stirrer for 24 h until clear solution was obtained. Following this, the pH of the clear Na alginate solution was adjusted in the range of pH 2, 3, 3.7, 4, 5, 6, and 7 using 1N HCl, 6 N HCl and 1 M NaOH (Figure 1). It is important to highlight here that according to the literature, the pKa of medium viscosity Na alginate ranges from 3.2 to 4.4, therefore we selected pH 3.7 as an approximation where protonated and deprotonated carboxylic groups become equal. Then the viscosity of sodium alginate solution at different pH was determined concerning the shear rate and shear stress to identify their Newtonian or non-Newtonian attributes using the Rheometer. Furthermore, the stability study of Na alginate solution from one source (VIVAPHARM® Alginate PHU 175) was conducted at different pH when stored under 2 – 8 °C and regular condition (25 °C/60% RH) for different timepoints, namely, t0 (initial), t1 (1 month) and t2 (3 months). At a defined time point, the aliquots of Na alginate stored under different conditions were pulled out and visual appearance was monitored as well as pH and viscosity was determined at each timepoint.

Table 1: Sodium Alginate source, macroscopic appearance of powder and solution and pH — **Table 1:** Sodium Alginate source, macroscopic appearance of powder and solution and pH

Table 2: Physical appearance of Na Alginate from different sources — **Table 2:** Physical appearance of Na Alginate from different sources

RESULTS

We observed a clear Na alginate solution at pH 7, 6, 5 and 4 (Figure 1). However, at pH values that fall below 3.7, macroscopic phase separation was noted. The rheological characterization of all four different Na alginate solutions revealed that as the shear rate increased from 0 to 1000 1/s, sodium alginate showed shear thinning behavior (Figure 2).

Figure 1: [A] Addition of HCl to sodium alginate solution leads to complete dissociation of HCl and sodium alginate and further addition of HCL resulting in alginic acid gel formation. [B] Chemical species in the system as pH decreases. [C]Graphical representation of increase in Viscosity with decrease in pH of Na alginate resulting in alginic acid gel. — **Figure 1:** [A] Addition of HCl to sodium alginate solution leads to complete dissociation of HCl and sodium alginate and further addition of HCL resulting in alginic acid gel formation. [B] Chemical species in the system as pH decreases. [C] Graphical representation of increase in Viscosity with decrease in pH of Na alginate resulting in alginic acid gel.

Out of four different Na alginates JRS-1 exhibited high viscosity at low shear rate and then more shear thinning at high shear rate than other Na alginates (MVG, JRS-2 or JRS-3) at pH 7, 6 and 5 at 25 °C and 37 °C. However, as pH further decreases to 4, 3.7, 3 and 2, Na alginate (MVG) exhibited comparable or higher viscosity than JRS-1 at 25 °C and 37 °C indicating enhanced intermolecular interactions at lower pH values (Figure 3).

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Source: Iram Maqsood, Surya T. Evani, Ahmed Ibrahim, Gary Hollenbeck, Venkata S. Akshintala, Stephen W. Hoag, Rheological and Stability Evaluation of Sodium Alginate as a Pharmaceutical Excipient Under Varying pH, University of Maryland School of Pharmacy, IPEC-AMERICAS Excipient World 2025 National Harbor, IFF, JRS Pharma, MII, Origin

Rheological and Stability Evaluation of Sodium Alginate as a Pharmaceutical Excipient Under Varying pH

excipients formulation