Abstract by Chengqian Zhang

Oral delivery of proteins in the form of tablets would be preferable to injection due to high patient compliance. The spray-drying technique is increasingly employed to prepare dry protein powders, which can then be compacted into tablets. However, the stability of proteins can be compromised during the spray-drying process and the subsequent compaction process. Therefore, excipients are generally required in protein formulations not only to preserve the stability of proteins upon drying and compaction, but also to improve the tabletability of spray-dried (SD) protein powders.

The objective of this PhD project was to evaluate the influences of different amino acids (AAs) on the stabilization, physicochemical properties, and tabletability of SD protein powders. The particle properties of different SD protein/AA powders and the physical as well as chemical integrity of proteins post-drying and compaction were characterized by various characterization techniques. In addition, the effects of AAs on the tabletability of different SD protein powders were investigated.

The five most representative AAs, that is, arginine (Arg), leucine (Leu), glycine (Gly), tryptophan (Trp), and aspartic acid (Asp), were selected from 20 natural AAs using principal component analysis (PCA) on 26 molecular descriptors. It was found that when using AAs as stabilizers, the charge of the AAs should be considered in addition to the commonly acknowledged water replacement and vitrification theories. This is because the basic and acidic microenvironmental pH values created by certain AAs (e.g., Arg and Asp) could compromise protein stability. In addition, the particle properties and solid forms of SD protein powders varied upon the type of AAs added, which consequently affected the storage stability as well as the tabletability of SD protein powders. In general, the addition of Leu could provide a better protective effect on SD protein powders from moisture uptake during storage than other AAs. The addition of Gly in SD protein powders exhibited higher compressibility than other AAs. The addition of Trp and Asp to SD protein powders resulted in an amorphous powder. Nonetheless, their effects on the stabilization and tabletability of SD protein powders did not exceed other AAs such as Leu and Gly. However, Arg appeared to be unsuitable for formulating SD protein powders due to its high hygroscopicity. This project indicates that AAs are promising excipients for both maintaining the stability and improving the tabletability of SD protein powders.