Analytical approach for lubricant characterization of excipients using the surface replication method.

Lubricants are indispensable pharmaceutical ingredients for preventing tableting failure due to powder adhesion to the die wall. The impact of lubricants was evaluated with use of the Binding Identification for Net Detriment (BIND) surface replication method. Raloxifene hydrochloride (RH) was selected as a model chemical with high adhesion, and four commercially available tablet lubricants - stearic acid, sodium stearyl fumarate, calcium stearate, and magnesium stearate - were used for RH formulation. BIND was applied to the die wall to analyze the effect of various lubricants on binding properties. The preparations without lubricants showed poor tableting properties as evidenced by as much as 61.7% powder adhesion density. Lubricants significantly altered the binding properties, yielding powder adhesion densities of 40.2% (stearic acid), 29.7% (stearyl sodium fumarate), 23.0% (calcium stearate), and 13.6% (magnesium stearate). Evaluation of three grades of magnesium stearate resulted in a two-fold difference between the highest and the lowest powder adhesion density. Throughout the work, conventional methods including visual observations and measurement of ejection force were unable to provide qualitative/quantitative evaluations. The ejection process depends on both axial force and radial force; however, the ejection force show only the axial force. At the same time, visual observation could release significant qualitative results. However, BIND allowed qualitative and quantitative analysis of the binding properties. BIND is a promising assessment method for analyzing the impacts of various lubricants on binding properties and for optimizing RH formulations.