Effect of amino acids on the compaction behavior and stability of spray-dried trypsin/lactose powder

Amino acids (AAs) have been employed as excipients in spray-dried (SD) protein formulations due to their stabilizing effects and particle engineering abilities. However, the research focusing on the influence of AAs on the tabletability of SD protein powders is still limited. The aim of this study was to investigate the effects of five diverse AAs, arginine hydrochloride (Arg·HCl), leucine (Leu), glycine (Gly), tryptophan (Trp) and sodium aspartate (Asp·Na), on the compaction behavior and stability of SD trypsin/lactose powders. The SD powders were characterized in terms of morphology, bulk powder properties, residual moisture content, and solid-state structure. Subsequently, the resulting powder compacts were characterized with respect to compressibility, compactability, and tabletability. Lastly, the conformational stability and enzymatic activity of trypsin in different SD formulations after compaction were assessed. The results showed that the SD trypsin/lactose/Arg·HCl powder exhibited the poorest tabletability. Moreover, SD trypsin/lactose/Leu powder showed relatively poor tabletability, while SD trypsin/lactose/Trp powder showed a moderate tabletability. On the other hand, SD trypsin/lactose/Gly powder displayed the best compressibility, and the SD trypsin/lactose/Asp·Na tablets exhibited the highest tensile strengths at high compaction pressures. However, an altered conformation and reduced enzymatic activity of trypsin were observed in the SD trypsin/lactose/Asp·Na formulation upon compaction. In conclusion, the addition of five different AAs to the SD trypsin/lactose powder system resulted in distinct compaction behaviors and stabilizing effects, which can be attributed to the intrinsic properties of the original SD particles, such as hygroscopicity, morphology, and potential AAs' surface distribution.