Effect of Mixing on the Lubrication of Crystalline Lactose by Magnesium Stearate

Abstract

It is well known chat magnesium scearace, used'as tablet lubricant, can form a continuous hydrophobic film around solid particles when nixing tines are too long, so that disintegration tine increases and nechanical strength of tablets fails. It was also shown in previous works chat the addition of colloidal silicon dioxide is in some cases able to interrupt the lubricant film, and allows to recover the good tabletting properties of sone mixtures.

This work studied the lubrication of crystalline lactose with magnesium stearate. A Turbula and a cubic mixer were used, and the properties of resulting tablets were studied on an excenter cablet press fitted out with strain gauges. It appeared that the hydrophobic film formation occurs after a very short time. This film formation depends not only of mixing cine, but also of the speed of nixing and die kind of mixer used. In the studied case, the lubricant film could not completely be broken by addition of colloidal silicon dioxide, and it seems not to be possible to produce good lactose tablets when the best mixing tine has been exceded.

Lactose is an interesting excipient at an economical point (if view, but its tabletting is not without difficulties : it needs bight compression forces and it is always necessary to add a lubricant.

Recent publications^1-5 have reported what an important influence on tablettability the mixing of an excipient with a lubricant may have. A bad mixing procedure can induce weaker mechanical properties and longer disintegration time of tablets.

This effect of the lubricant can be described by invoking at least three different mechanisms:

adsorption or surface contact adhesions

This bad effects were reported for several products, but it seems that the degree of the effect depends of the kind of lubricant and the physical structure of the excipient : for example, the polytetrafluoethylene used as lubricant, seems not to induce bad properties to the mixture ³, and dicalcium phosphate dihydrate (Emcompress) seems to be an excipient which properties ^1–2 are not influenced badly by any lubricant'. The effect of the lubricant, especially of magnesium stearate, seems, according to De Boer, Bolhuis and Lerk² to be dependent on the compression behavior and the bonding mechanism of the excipient. These authors² make a difference beetween excipients which, under pressure, present a plastic deformation of particles followed by bonding of adjacent surfaces, and other excipients which consolidate by extensive fragmentation; they reported several-publications in which powders as potassium chloride or starch were classified in the first category, anmd sucrose, lactose, or dicalcium phosphate dihydrate were included in the second.

For all these reasons the effect of a lubricant on the tabletting properties of an excipient are not undoubted, and often difficult to anticipate without further studies.

As a part of a study of tabletting of crystalline lactose, the effects of nixing of lactose with sutgnesiiMi stearate were studied with more accuracy in this work.