PT  - JOURNAL ARTICLE
AU  - Oliyai, Cecilia
AU  - Patel, Jitendra P.
AU  - Carr, Linda
AU  - Borchardt, Ronald T.
TI  - Solid State Chemical Instability of an Asparaginyl Residue in a Model Hexapeptide
DP  - 1994 May 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 167--173
VI  - 48
IP  - 3
4099  - http://journal.pda.org/content/48/3/167.short
4100  - http://journal.pda.org/content/48/3/167.full
SO  - PDA J Pharm Sci Technol1994 May 01; 48
AB  - The chemical stability of an Asn-hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) in lyophilized formulations was evaluated as a function of the pH of the bulk solution, temperature, and residual moisture content in a factorial study. Degradation pathways and product distribution in solid state were determined and characterized. It was shown in this study that the pH of the starting solution had a significant effect on the rate of deamidation and product distribution. In general, better stability for the Asn-hexapeptide was achieved at a slightly acidic pH range (3–5) in the solid state. The effects of residual moisture level and temperature on peptide stability proved to be less significant. A statistically significant two-factor interaction indicated that the pH of formulation solution determined the extent to which the peptide stability depends on moisture level and temperature. In general, the degradation of the Asn-hexapeptide in the solid state was similar to that observed in solution, except for the observation that no iso Asp-hexapeptide was detected at pH 5.0 in the solid state, whereas this was the major degradation product in solution.