Peptide and protein biologics present oral solid dosage form (OSDF) challenges around processability, stability, and broad dosage range, particularly those that have been dried via spray-drying or lyophilization. Excipient choice is critical to attaining OSDF quality and functionality. For this talk, tablets were produced with lactoferrin as protein API at concentrations ranging from high (45%) to medium (30%) to low (15%). The lactoferrin used in this study was less than 50 microns in particle size and cohesive. Tablets were produced by direct compression (DC) and dry granulation (DG). Formulating with microcrystalline cellulose (MCC) produced tablets with tensile strength and friability ≥1 MPa and ≤0.75% weight loss, respectively. Lactoferrin release from tablets containing MCC was sensitive to change in compression force, so tablets containing MCC needed 2.5% croscarmellose to attain consistent release at different compression forces. Formulating with lactose provided consistent release at different compression forces, but friability was ≥0.75-1% weight loss, thus requiring high compression force to attain suitable physical properties. DG slightly reduced tablet strength, but generally provided greater lactoferrin uniformity (% RSD ≤5%). Different modes of release could be attained, depending on excipient selection. No protein-excipient compatibility issues were observed.
Learning Objectives:
Understand challenges related to formulating biomacromolecules, like proteins and peptides, into oral solid dosage forms (OSDFs), such as tablets.
Formulate across a broad range of biologic API concentration using a fine particle size, cohesive protein powder.
Demonstrate impacts of excipient choice and manufacturing process operations on OSDF properties, performance, and stability.