Porous Silica Gel Glidants Aid Direct Tablet Compression

Efficiency and productivity are two important factors considered when selecting a solid-dosage formulation method. For that reason, direct compression (DC) is an attractive option because it is simpler than wet or dry granulation. “Direct compression has several advantages over wet/dry granulation processes. It involves fewer steps, lower costs, better dissolution of the API, and most importantly, DC does not require heat, moisture or long drying times, thus making it ideal for moisture/heat sensitive APIs,” says Chitra Sundararajan, lab manager at the Indian Knowledge Center of Grace Materials Technologies. She also notes that generally, DC is considered as the first choice by formulation scientists. When the API is present in large amounts, or when the API has poor flow or compaction properties, then wet/dry granulation techniques are considered. Because direct compression (DC) involves compaction of the tableting mixture without any prior granulation, it is more efficient and cost-effective, there is reduced chance for contamination due to the shorter processing time, and with fewer unit operations, there are fewer validation and documentation requirements (1).

Solid-dosage formulations designed for DC consist mainly of the API, binder, filler, disintegrant, and lubricant (1). These ingredients are selected for a given API and dosage level by considering their compactability and flow properties. The required amount of API and its compaction properties will determine the choice of binder, filler, or blend. Flow is crucial because without proper flow, weight variations and/or nonuniform distribution of the API can result. Glidants used at 0.1–2.0% of the formulation can help manage the flow characteristics of direct compression formulations.

The role of the glidant
The glidant keeps the pharmaceutical formulation constituents flowing freely and consistently, according to Bill McCarthy, global marketing manager for Grace Materials Technologies. “Appropriate flow is necessary in both granulation and tableting to ensure that each tablet or granule has a consistent proportion of all of the ingredients (uniform content),” he explains. The effect of a glidant on the flow of the tablet formulation depends on the shape and size of the glidant particles and those of the other components. “The flow of the final mixture depends on a combination of several factors; in addition to particle size, molecular interactions, tribo-electrostatic charges, the presence of polar groups, and capillary forces all play a role,” explains Sundararajan. The procedure for addition of the glidant can also impact its performance.

Good glidants, according to McCarthy, are materials that are inert, have particle sizes smaller than those of the active and other excipient components, thus enabling these typically larger particles to slide past one another, and have adsorptive capacity in order to keep water from causing agglomeration. Porous silica gel is a particularly effective glidant because it has all of these characteristics, including a massive capacity for water, and thus can absorb moisture and improve the stability of APIs. 

It should be noted that the silica glidants offered by Grace, which are silica gels, are not the same as other silicon dioxides on the market, which are generally fumed (colloidal). The Syloid products from Grace are manufactured as micronized particles with a highly developed network of well-defined mesopores (greater internal surface area) and an internal porosity that can be controlled. They also have a higher density and thus create less dust, according to Sundararajan.

Benefits of two-step mixing
Traditionally, the glidant has been added only to the API and then API and excipient mixture are blended before compaction. The researchers at Grace have found, however, that incorporation of different silica glidants in both the API and excipient components of a formulation results in not only improved flow properties, but also enhanced moisture control, stability, and uniformity, according to Sundararajan. “The benefit of two-step mixing with our silica materials is increased micronized excipient/excipient and excipient/API particle compatibility, and that more silica is available to form a layer around the API particles, which improves flow, uniformity, and stability,” she says. Porous silicas can also increase tablet hardness at lower compression forces, decrease friability, capping, and lamination, and act as anti-static agents.

Solving moisture-sensitive API issues
In addition to their beneficial use as glidants for direct compression, porous silicas can also help control moisture. APIs that are moisture-sensitive present a challenge. During manufacturing, they can cause caking and poor flow properties. Once in final tablet form, moisture absorption can lead to chemical degradation, changes in dissolution rates, and a decrease in the shelf life of the drug. As a result, pharmaceutical companies often turn to specialty packaging solutions, which can add cost to the final product.

Porous silicas may provide an alternative solution. The researchers at Grace have shown that, for moisture-sensitive APIs, two different silica glidants can be used in each part of the tablet formulation—one for flow improvement and one for both flow improvement and moisture absorption. “We were able to demonstrate that incorporation of a silica known for moisture absorption at up to 20% (for lower dosage formulations) in the API mixture and a silica recognized for its glidant properties in the excipient mixture (1%) provides tablets with acceptable hardness, friability, weight uniformity, and other characteristics,” she explains. It is important though, Sundararajan adds, to optimize the ratios of the different silica excipients for different APIs.

References

1. G. Kumar et al., Intl. J. Res. Pharm. and Biomed.Sci. 4 (1) 155-158 (2013).