Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme.

ABSTRACT

Oral administration is advantageous compared to the commonly used parenteral administration for local therapeutic uses of biologics or mucosal vaccines, since it can specifically target the gastrointestinal (GI) tract. It offers better patient compliance, even though the general use of such a delivery route is often limited by potential drug degradation in the GI tract and poor absorption. Using bovine serum albumin (BSA) and lysozyme as two model proteins, we studied their solid-state properties, mechanical properties, and tabletability as well as effects of compaction pressure, particle size, and humidity on protein degradation. It was found that BSA and lysozyme are highly hygroscopic, and their tablet manufacturability (powder caking, punch sticking, and tablet lamination) is sensitive to the humidity. BSA and lysozyme exhibited high plasticity and excellent tabletability and remained amorphous at high pressure and humidity. As for protein stability, lysozyme was resistant to high pressure (up to 300 MPa) and high humidity (up to 93%). In contrast, BSA underwent aggregation upon compression, an effect that was more pronounced for smaller BSA particles. High humidity accelerated the aggregation of BSA during incubation, but it did not further synergize with mechanical stress to induce protein degradation. Thus, compression can potentially induce protein aggregation, but this effect is protein-dependent. Therefore, strategies (e.g., the use of excipients, optimized manufacturing processes) to inhibit protein degradation should be explored before their tablet dosage form development.