Understanding and optimizing the dual excipient functionality of sodium lauryl sulfate in tablet formulation of poorly water soluble drug: wetting and lubrication

Abstract

Purpose: To evaluate and optimize sodium lauryl sulfate (SLS) and magnesium stearate (Mg.St) levels, with respect to dissolution and compaction, in a high dose, poorly soluble drug tablet formulation.

Methods: A model poorly soluble drug was formulated using high shear aqueous granulation. A D-optimal design was used to evaluate and model the effect of granulation conditions, size of milling screen, SLS and Mg.St levels on tablet compaction and ejection. The compaction profiles were generated using a Presster^© compaction simulator. Dissolution of the kernels was performed using a USP dissolution apparatus II and intrinsic dissolution was determined using a stationary disk system.

Results: Unlike kernels dissolution which failed to discriminate between tablets prepared with various SLS contents, the intrinsic dissolution rate showed that a SLS level of 0.57% was sufficient to achieve the required release profile while having minimal effect on compaction. The formulation factors that affect tablet compaction and ejection were identified and satisfactorily modeled. The design space of best factor setting to achieve optimal compaction and ejection properties was successfully constructed by RSM analysis.

Conclusions: A systematic study design helped identify the critical factors and provided means to optimize the functionality of key excipient to design robust drug product.

Keywords::

• Wetting agent
• design of experiment
• sodium lauryl sulfate
• magnesium
• stearate
• lubricant
• compaction

Acknowledgments

Opinions expressed in this research are those of the authors. For the author (ZD) affiliated with FDA, the opinions do not necessarily represent the views of the agency.

Declaration of interest

The authors report no conflicts of interest.