Sodium Starch Glycolate

Starch is a generic term for carbohydrate particles found in many plants. Starch grains swell in contact with water, and this appears to be an important property that relates to their use as tablet disintegrants. Sodium starch glycolate is the sodium salt of cross-linked carboxymethylated starch (chemically modified starches). When viewed under the microscope it has the characteristic appearance of starch grains, but with small particles of sodium glycolate and sodium chloride adhering to the surface of the starch grains.

The polymeric structure of sodium starch glycolate.
Fig. 1: The polymeric structure of sodium starch glycolate.

There are many different sources and several different grades of sodium starch glycolate available using different sources of starch, and different types and levels of cross-linking. These differences have a significant influence on the choice of the appropriate grade for a particular application and process.

Pharmaceutical Use as a Superdisintegrants

Superdisintegrants represent a new generation of disintegrants, significantly more effective and requiring lower concentrations compared to traditional disintegrants. The first superdisintegrant to be introduced was sodium starch glycolate. The development was probably inspired by a need to have a disintegrant that was effective at lower concentrations and could be used more easily in direct compression formulations.

Manufacturing of Sodium Starch Glycolate

Sodium starch glycolate is manufactured from native starch by first crosslinking the starch using either an aqueous solution of sodium trimetaphosphate or by dehydration. Cross-links form between adjacent chains on the starch grain’s surface. The cross-linked starch is isolated, dried, and then reacted with sodium monochloroacetate to create carboxymethylated cross-linked starch. This reaction is conducted in an organic solvent, usually denatured ethanol or methanol. Ethanol, a Class III solvent, may be preferred over methanol, a Class II solvent, unless there are other overriding considerations. After neutralization, the sodium starch glycolate is washed to remove reaction by-products (sodium glycolate and sodium chloride) and dried. Because it is manufactured in a hydrophilic organic solvent, and due to the structure of the starch grains, residual solvent levels are typically around 4–5% w/w by loss on drying.

The Effect of Cross-Linking and Substitution of SSG on Disintegration Efficiency

Sodium starch glycolate (SSG) exhibits varying degrees of cross-linking, degrees of substitution, and levels of neutralization. These variations contribute to the existence of different commercial grades of SSG in the global market. The alterations brought about by these variations can significantly impact the final material, influencing the success or failure of formulation development projects. Therefore, not all sources and grades of SSG are interchangeable for every application, with some being more suitable for specific processes.

Among these factors, the degree of substitution has a lesser effect compared to the degree of cross-linking. These two modifications produce opposite effects. This indicates an optimal combination of substitution and cross-linking, and the commercially products are typically optimized to meet this balance. Additionally, the disintegration efficiency of SSG can be enhanced by reducing sodium chloride content. Sodium chloride competes with SSG for water absorption. This competition slows the swelling rate of SSG in the tablet matrix.

Considerations for Selecting Sodium Starch Glycolate

An important consideration when using sodium starch glycolate (SSG) in the wet mixing step of aqueous granulation is the selection of the appropriate grade. During the wet massing operation, SSG absorbs water and swells. In their swollen state, SSG particles become more fragile and susceptible to mechanical damage, particularly in high-speed mixer granulators. If the integrity of SSG particles is compromised during this process, disintegrant activity is lost, while wet binder activity is gained. This leads to increased tablet disintegration time and decreased dissolution of the active pharmaceutical ingredient (API).

The impact of wet granulation on SSG’s disintegration efficiency with varying substitution and cross-linking degrees has been studied. Findings show that higher cross-linking reduces swelling. This makes starch grains less prone to mechanical damage during wet massing. Increased cross-linking enhances the strength of hydrated grains. It minimizes the distention of the amylopectin coat. Additionally, it directly strengthens the coat through extra cross-linking.

Reference:

  • Augsburger, L. & Hoag, S. (2008). Pharmaceutical Dosage Forms Tablets volume 2: Rational Design and Formulation. New York: Informa Healthcare.