Preformulation development of recombinant pegylated staphylokinase SY161 using statistical design
Journal Title: The AAPS Journal - Year 2002, Vol 4, Issue 4
Abstract
The goal of this study was to perform preformulation development of SY161 by using statistical design methods to understand the effects of buffer strength, NaCl concentration, and pH on conformation and stability of the protein. It was also important to elucidate interactions between these factors. A central composite design using a 2-level full-factorial study was performed. Secondary structure was evaluated using circular dichroism. Stability toward unfolding was investigated using high-sensitivity differential scanning calorimetry. Depegylation, aggregation, and protein loss were evaluated using SEC-HPLC with on-line light scattering, at time zero and after a 2-week stability study. Response surface plots clearly show optimal pH, NaCl, and buffer conditions. Interactions between pH and NaCl as well as pH and buffer concentration are observed. Tm is seen to be predictive of SY161 stability. Secondary structure changes were minimal and did not influence stability. Statistical design was very effective in providing an understanding of the effects of the formulation components on SY161 stability.
Authors and Affiliations
Frank Bedu-Addo, Randall Moreadith, Siddharth J. Advant
Keywords
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- EP ID EP682009
- DOI 10.1208/ps040419
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