Chemical pathways of peptide degradation. VII. Solid state chemical instability of an aspartyl residue in a model hexapeptide.

摘要: The chemical stability of an Asp-hexapeptide (Val-Tyr-Pro-Asp-Gly-Ala) in lyophilized formulations was evaluated as a function multiple formulation variables–specifically pH the bulk solution, temperature, moisture content, and type bulking agent (amorphous vs. crystalline). disappearance starting solid state conformed to pseudo-first-order reversible kinetics. This degradation profile accounted for by product distribution. factorial experimental design this study allowed statistical analysis effects individual variable (main effects) well those two-factor interactions on Asp-hexapeptide. Analysis Variance (ANOVA) calculations main indicated that while influence solution not statistically significant, residual level, and, especially, had significant impact reactivity hexapeptide. Furthermore, depending which excipient used formulations, level temperature could be important variables. These types experiments have proven useful rapid identification variables given system consequently, optimization formulations.