Magnesium Stearate
For many decades, this excipient with GRAS (Generally Recognized As Safe) status has been widely used in the food, nutraceutical and pharmaceutical industry as an anticaking, lubricant, release, and antifoaming agent. It is present in many food supplements, confectionery, chewing gum, herbs and spices, and baking ingredients.
Then why has the industry started talking about finding alternatives to this versatile and supposedly safe and robust inactive additive?
1. Impact on tablet hardness
It is a well-known fact that Magnesium Stearate could lead to a drastic decrease in tablet hardness because it blocks the formation of inter-particle bonds. This is even more manifested on over-mixing or production scale-up where the tablet hardness decreases as the batch compression continues, due to the overmixing of Magnesium stearate in the feeder system.
2. Impact on disintegration and dissolution
It’s mechanism of action being formation of slippery hydrophobic film that reduces friction in the die wall, the very same film could lead to prolonged disintegration and dissolution times, as observed in studies.
3. Batch to batch variation
With this excipient available as several different hydrates and the wide specification limits, the commonly observed variation in the molecular, structural and crystal properties lead to pronounced impact on lubrication efficiency, disintegration times and dissolution. In short, the robustness of the process as well as product quality is uncertain.
4. Sustainability
This topic has been an important catalyst in the decision making process of choosing raw materials in the last 5 years. Magnesium stearate, majorly sourced from palm oil, has a low sustainability metrics, thus, a sustainable alternative would be welcomed by the industry with open arms.
5. Questionable safety
This is a concern, especially in the food supplement industry, as the intake of this excipient is not limited by the daily dosage. Magnesium Stearate has been associated with GMO risks, cardiovascular effects, bioavailability reduction, and inhibition of nutrient absorption, allergies, and impact on immune system among other issues. Although none of these claims have been explicitly proven, taking public perception into consideration, companies are in search of a safer replacement.
In spite of these risks, the industry has been using magnesium stearate for the lack of no better alternative. Existing options either compromise on the lubricant effect or adversely affect the disintegration/dissolution time.
Figure 1: Loss of tablet hardness in correlation to the mixing time for different lubricants
While good lubrication is required to run a smooth tableting process, most tablets with added lubricants will show lower tablet hardness than those without added lubricant. The loss in tablet hardness (lubricant sensitivity ratio) depends on the type of lubricant and the components of the tableting mixture (excipients and APIs). Moreover, the mixing method (e.g. mixer type) and the mixing time can have a strong influence on the loss of tablet hardness.
Figure 1 shows the loss of tablet hardness for the new CompactCel® lubricant premixes in comparison to the unwanted artificial lubricant. The CompactCel® LUB (Food) product shows the lowest loss of tablet hardness and no significant change of the tablet hardness even after prolonged mixing. The CompactCel® LUB (Pharma) product initially shows a similar loss of tablet hardness as the unwanted artificial lubricant. However, there is no further loss of tablet hardness observed indicating that the material does not bring about the danger of mixing time induced overlubrication.
Addressing this issue, BIOGRUND has developed a safe and robust CompactCel® LUB, an easy-to-use lubricant premix, that has little to no negative impact on hardness, disintegration and dissolution, even on overmixing.
Figure 2: Efficiency of lubricants measured by tablet ejection force