چکیده (انگلیسی):

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 (SCXHPLC)
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°C to 50° C is ln(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.