UNDERSTANDING SOURCES OF VARIABILITY AND QUALITY IN MODERN SOLID ORAL DOSAGE FORMS

Pharmaceutical manufacturing of solid oral dosage forms is undergoing a significant evolution with the introduction of continuous manufacturing and advanced manufacturing technologies such as three-dimensional printing (3DP). Pharmaceutical manufacturing requires new approaches to ensure the quality of excipients and new ways to design and formulate advanced solid oral dosage forms. One example of a raw material that has quality issues is magnesium stearate, the most commonly used excipient in solid oral dosage forms. The complicated physicochemical nature of magnesium stearate introduces variability to the performance of tablet lubrication and dissolution. The lack of understanding on this variability can cause product loss or failure of quality assessments. In addition, new manufacturing methods such as 3DP binder-jet printing of pharmaceuticals have poorly understood quality challenges that need to be explored.

The specific aims of this project are as follows: [1] To determine the susceptibility of the disordered form to form interconversion and disproportionation when used to make a tablet. The comparison of lab synthesized samples to the more relevant forms that appear in commercial products such as the monohydrate and dihydrate forms of magnesium stearate are included. 13C labeled magnesium stearate of all forms will be prepared to determine which causes the greatest extent of disproportionation.

[2] To determine if a newly investigated form of magnesium stearate, named the disordered form, is viable for pharmaceutical use. The disordered form must minimize risk impacting dissolution while being an effective lubricant, thereby reducing batch and continuous manufacturing failures.

[3] To evaluate how 3DP printed tablet manufacturing methods impact critical quality attributes. This work will identify the importance of attributes such as weight; binder composition; excipients; compatible drugs; software; hardware change as a function of raw material attributes (API, powder character, and binder) and critical process parameters.