Investigation of Dispersion Kinetics of Particulate Lubricants and their Effect on the Mechanical Strength of MCC Tablets.

ABSTRACT

INTRODUCTION: Tablets are commonly produced by internally adding particulate lubricants, which are known to possibly lower the mechanical strength of tablets. This reduction is caused by the coverage of matrix forming components by lubricant particles, resulting in decreased interparticulate interactions. The known incompatibilities with some active compounds of the predominantly used lubricant, magnesium stearate, call for the in-depth characterization of alternative lubricants. PURPOSE: Investigation of the dispersion behavior of five commonly applied pharmaceutical lubricants by mathematically modeling the dispersion kinetics for short and extended mixing times. METHODS: The dispersion behavior of five different pharmaceutical lubricants were examined by systematically varying lubricant concentration and mixing time of binary formulations and evaluating the kinetic of tensile strength reduction by theoretically estimating the surface coverage based on particle sizes. RESULTS: For short mixing times, a unifying relationship between compactibility reduction and theoretical surface coverage was identified. Subsequently, for extended mixing times, distinct differences in the shear strength and dispersion kinetics of the investigated lubricants were found. CONCLUSIONS: The lubricant particle size controls the tensile strength reduction if short mixing times are applied. For extended mixing times, the investigated lubricants can be divided into two groups in terms of dispersion kinetics. Possible underlying reasons are discussed in detail in order to enhance the general understanding of lubricant dispersions in tablet formulations.