Kinetics of pramlintide degradation in aqueous solution as a function of temperature and pH

AAPS PharmSciTech. 2000 Mar 18;1(2):E7. doi: 10.1208/pt010207.

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 reversed-phase (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 determination versus 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 degrees C to 50 degrees C is ln(k(0))= 37.39-21.900/RT, where k(0) 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 degrees C. The formulated pramlintide drug product has acceptable shelf life for long-term storage at 5 degrees C and up to a 30-day patient use when stored at ambient temperature.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Amyloid / pharmacology
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Ion Exchange / methods
  • Drug Contamination
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Islet Amyloid Polypeptide
  • Kinetics
  • Molecular Sequence Data
  • Reference Standards
  • Solutions
  • Temperature*
  • Time Factors
  • Water / chemistry
  • Water / metabolism

Substances

  • Amyloid
  • Islet Amyloid Polypeptide
  • Solutions
  • Water
  • pramlintide