Abstract
The stability of the 37-amino acid peptide pramlintide, in aqueous solution, was studied as a function of pH and temperature. Samples of pramlintide formulated as a parenteral product were exposed to elevated temperatures and to realistic storage conditions for as long as 30 months. Pramlintide degradation was monitored by three high-performance liquid chromatography (HPLC) methods: a reversedphase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method for percentage purity determination by area normalization, plus a second RP-HPLC method for potency determinationversus external standards. The pH-rate profile for pramlintide shows increasing degradation rate constants with increasing pH over the range pH=3.5 to 5.0. The Arrhenius expression for pramlintide degradation at pH=4.0 over the temperature range 5°C to 50°C is In(k0)=37.39−21.900/RT, where k0 is the zero-order rate constant (in %/mo) for pramlintide degradation. The pramlintide parenteral product formulated at pH=4.0 is extremely stable, with percentage purity and percentage potency loss of only approximately 2% over 30 months at 5°C. The formulated pramlintide drug product has acceptable shelf life for long-term storage at 5°C and up to a 30-day patient use when stored at ambient temperature.
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Kenley, R.A., Tracht, S., Stepanenko, A. et al. Kinetics of pramlintide degradation in aqueous solution as a function of temperature and pH. AAPS PharmSciTech 1, 7 (2000). https://doi.org/10.1208/pt010207
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DOI: https://doi.org/10.1208/pt010207