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

被引：5

作者：

Kenley R.A. ^{[1
]}

Tracht S. ^{[1
]}

Stepanenko A. ^{[1
]}

Townsend M. ^{[2
]}

L'Italien J. ^{[3
]}

机构：

[1] Cabrillo Facility of Magellan Laboratories Inc., San Diego, CA 92126

[2] ISIS Pharmaceuticals Inc., Carlsbad, CA

[3] Baxter Hyland, Glendale, CA

来源：

AAPS PharmSciTech | / 1卷 / 2期

关键词：

Arrhenius; Hydrolysis; Orthogonal separation; pH; Pramlintide; RP-HPLC; SCX-HPLC;

D O I：

10.1208/pt010207

中图分类号：

学科分类号：

摘要：

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°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.

引用

页数：7

共 14 条

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