What are the softening effects produced by magnesium stearate in the direct compression process?

Magnesium stearate is one of the most used lubricants in pharmaceutical and food processes. However, in the research and production of tablets, it is found that the addition of magnesium stearate has a certain softening effect on tablets, which is mainly manifested in the reduction of tablet hardness and the improvement of tablet brittleness, mainly due to the fact that magnesium stearate can change the bonding force between the particles of excipients, which in turn alters the nature of excipients for compression tableting.
The magnitude of the softening effect of magnesium stearate on the material is affected by a variety of factors, including the characteristics of the direct-pressing excipient, the physical and chemical properties of magnesium stearate itself, the concentration of magnesium stearate, and the length of time that the excipient is mixed with the magnesium stearate.
Physical and chemical properties of magnesium stearate
Magnesium stearate is a white, fluffy, non-gritty fine powder with a slight peculiar odor. It has hydrophobicity and extremely strong adsorption.
Different synthesis and production processes result in different properties of magnesium stearate, specifically in particle size and morphology and other differences, and these differences also lead to different lubricating effect of magnesium stearate. In addition, through the comparison found that particle size smaller, larger specific surface area of magnesium stearate lubrication effect is better, in other words, may be such a magnesium stearate is more prone to over-lubrication phenomenon, i.e., softening effect.
Effect of direct-pressing excipients on the sensitivity of magnesium stearate
The strength of the sensitivity of direct-pressing auxiliaries to magnesium stearate is expressed by lubricant sensitivity ratio (LSR), LSR=1-N/N0, N0 indicates the hardness of direct-pressing auxiliaries pressed into tablets without magnesium stearate, and N indicates the hardness of magnesium stearate-containing hardness.The value of LSR is high, indicating that the direct-pressing auxiliaries have a strong sensitivity to magnesium stearate, are greatly influenced by magnesium stearate, and the softening effect is obvious. The influence of the softening effect is obvious.
According to the deformation of the direct-pressing auxiliaries after being pressed, the direct-pressing auxiliaries can be divided into 3 categories: elastic auxiliaries, plastic auxiliaries and brittle auxiliaries. Elastic excipients refers to the material particles deformation occurs after compression, when the force is withdrawn and returned to the original state of a class of excipients, such as starch class of direct pressure excipients (both viscous); plastic excipients refers to the material particles deformation occurs after compression, but does not occur after the withdrawal of the force elasticity of the restoration of such materials as microcrystalline cellulose, etc.; brittle excipients refers to the material particles after compression, the rupture occurs, into a smaller particle size , such as lactose and calcium phosphate. Each category of excipients is affected by magnesium stearate to a different degree in tableting, with magnesium stearate having a significant effect on elastic and plastic excipients that are capable of deformation in tableting.
In general, the three types of excipients were affected by magnesium stearate in the following order: elastic excipients > plastic excipients > brittle excipients.
Particle size affects the sensitivity of excipients to magnesium stearate
Particle size is the most basic property of powders and can determine other properties of powders. For direct pressure excipients, it is required to have good fluidity, and in general, the particle size and powder fluidity is positively related, the larger the particle size the better the fluidity, but different particle size affects the sensitivity of excipients to magnesium stearate.
The different particle sizes of microcrystalline cellulose were investigated as affected by magnesium stearate, and larger particle sizes had stronger sensitivity to magnesium stearate. The experimental results showed that the disintegration rate increased rapidly with increasing particle size, and the hardness of the tablets decreased with increasing mixing time. Mixing time of excipients with magnesium stearate affects the degree of softening
In the production process of tablets, the mixing time of materials is an important parameter, too short a time, the materials may not be mixed uniformly, and in the case of materials containing magnesium stearate as a lubricant, the prolongation of the time may bring a series of side effects.
Direct pressure excipients cellulosic, starch, and lactose are affected by the length of mixing time. The hardness of tablets decreases with prolonged mixing time, and compound excipients also exhibit lubrication sensitivity. Concentration of Magnesium Stearate Affects Softening
The amount of magnesium stearate used in pharmaceutical processes is not strictly limited, and the Pharmaceutical Excipients Handbook recommends a concentration of 0.25% to 5.0% (W/W). Because of its hydrophobicity, which delays the disintegration and dissolution rate of solid drugs, it is required to be used in the lowest possible amount. In addition to this, high concentrations of magnesium stearate can severely reduce the hardness of tablets.
Reasons for the softening effect of magnesium stearate
The strong adsorption effect of magnesium stearate will form a layer of lubricating film on the surface of the material, which is not uniformly distributed in the central part of the tablet, and the thickness of the film is smaller than the edge of the tablet, and the thickness of the film in the central area of the tablet is only 2.5um when the concentration of magnesium stearate is 1.27%.
This film thus blocks the contact and force between particles. The lubricating film has obvious effect on the change of powder fluidity, from the principle of the action of the flow aid magnesium stearate doped into the powder, the fine particles of magnesium stearate are adsorbed on the surface of the powder particles, which can fill up the depressions of the particle surface, fill up the level, and reduce the roughness of the surface of the particles, so as to achieve the reduction of the friction between the particles, and to improve the fluidity of the powder.