Excipient Screening and Spray Drying Process Optimization of Cell-based and Protein-based Biologics with Feasibility Demonstration of Oral Delivery

Abstract

Biologics-based therapeutics, such as proteins and cells, have gained increasing popularity over the past few years. Formulation and process strategies have been applied to achieve quality biologics products, prioritizing desired efficacy and safety over shelf –life. In this thesis research, spray drying formulation development strategies were developed for a novel biotherapeutics ABAB antibody producing Sb-ABAB cells for the treatment of Clostridium difficile infection (CDI) and a recombinant human serum albumin (rHSA) using carbohydrate, protein-based, or other excipients and excipient combinations. Excipient functionality was explored using spectroscopy-based chemometrics investigation. In addition, novel mass spectroscopy based in cell-fast photochemical oxidation of proteins (ICFPOP-MS) was used in combination with homology labeling to probe the excipient - protein interactions. In addition, excipients and water activity effects on the storage stability of the Sb-ABAB spray dried product were explored to optimize shelf life. Subsequently, multivariate data analysis and design of experiments (DOE) were applied to explore the effects of spray dry process parameters on critical quality attributes of the protein- based and cell-based biological products. The spray dried protein/cell powders were further developed into oral dosage forms acceptable for patient use, such as tablets and capsules. The feasibility of developing oral protein tablets using IgG as model protein and enteric-coated Sb-ABAB capsules were explored. For example, compression force, particle size and storage relative humidity effects on the stability of the IgG tablets were investigated via analytical and biophysical analysis. In addition, colon targeted delivery of the Sb-ABAB minicapsules was developed and in vitro release assay was conducted to evaluate the enteric coating efficiency.

In conclusion, cell-based and protein-based therapeutics were successfully spray dried while achieving desirable stability during the drying process. Furthermore, protein tablets and controlled release Sb-ABAB capsules were successfully developed, offering a novel alternative delivery approach to biologics products.