FK906, a tripeptide, has been used as a model compound to study the effect of excipients on the glass transition temperature for peptides and related compounds in the frozen solution and lyophilized states. Three kinds of excipients were chosen for study, low molecular weight sugars, high molecular weight polymers and salts. Our results indicate that the Gordon-Taylor equation can be used to predict the glass transition temperature of FK906 in the presence of sucrose, lactose, trehalose and maltose in the frozen solutions and in lyophilized products. Dextrans having different molecular weights can have different effects on the glass transition temperature of FK906 in the frozen state. Cooling rate can also have an effect on the glass transition temperature for FK906 frozen solutions in the presence of dextran. Finally, salts have a significant effect on the glass transition temperature of FK906 in the frozen state but not in lyophilized FK906.

Antihypertensive Agents↗

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Some physicochemical properties of FK906: glass transition and relaxation.

FK906, a tripeptide antihypertensive agent, was used as a model compound to study some physicochemical properties of peptides and peptide-related compounds. Our results indicate that lyophilization, grinding and melting or storing the samples under conditions of high relative humidity affect chemical stability and crystallinity of FK906. In a preliminary study of lyophilization process design, an extended phase diagram for FK906 in aqueous solution was constructed, and the effects of cooling rate and and heating rate on the glass transition temperatures of lyophilized FK906 and the FK906 solution were investigated. Following lyophilization, the DSC thermogram of FK906 exhibits an endothermic peak whose area is storage temperature- and time-dependent. The endothermic peak shifts to higher temperatures as the heating rate is increased. Our results indicate that the endothermic peak is related to structural change during incubation of lyophilized FK906.

Antihypertensive Agents↗