ABSTRACT
A primary driving force for the creation and development of novel delivery systems was the advent of biotechnologically derived pharmaceuticals. Most protein and peptide pharmaceuticals are formulated for intravenous or subcutaneous injection; however, many patients have an adverse reaction to needles, and the desire for alternate dosage forms sets new expectations for the industry. Furthermore, these biomolecules often have limited solubility and/or aggregate with loss of activity. In many cases, aggregation, gelation, and precipitation occur, resulting in irreversible denaturation, precipitation, and stability issues. Reversible aggregation, usually marked by increased viscosity, may be acceptable if manufacturing fi ltration steps and syringability issues are alleviated (1). These formulation challenges are further accentuated by the need for an effi cacious dose in a small volume, and thus, formulation strategies at relatively high protein concentrations, where aggregation is a bimolecular degradation pathway and concentration dependent, become increasingly diffi cult.
