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

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.

journal_name

AAPS PharmSciTech

journal_title

AAPS PharmSciTech

authors

Kenley RA,Tracht S,Stepanenko A,Townsend M,L'Italien J

doi

10.1208/pt010207

keywords:

subject

Has Abstract

pub_date

2000-03-18 00:00:00

pages

E7

issue

2

issn

1530-9932

journal_volume

1

pub_type

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