چکیده (انگلیسی):

The article examines the effects of
temperature excursions and actual dose withdrawal on
the quality of pramlintide injection, a multidose liquid
parenteral formulation. Studies were designed to
demonstrate product robustness under conditions that
may occur during patient use. Pramlintide %Purity was
determined by two high-performance liquid
chromatography (HPLC) methods, a reversed-phase
(RP-HPLC) and a strong-cation exchange (SCX-HPLC)
method. A second RP-HPLC method was used to
determine pramlintide potency and the concentration of
the m-cresol preservative. Antimicrobial preservative
effectiveness testing was per USP and European
Pharmacopeia (Ph. Eur.). Short-term stability studies
were undertaken to probe the effects of the following
conditions: 5 °C to 40°C and 5°C to –20° C temperature
cycling over 10 days; once daily or four-times daily dose
withdrawal over 12 or 42 days; and combined 30° C
storage and four-times daily dose withdrawal over 42
days. In all cases, pramlintide %Purity and potency
values remained essentially unchanged or unchanged
relative to controls. Similarly, product appearance, and
m-cresol concentration and preservative effectiveness
were not significantly affected by the stress conditions
used in the 5 studies. Pramlintide injection drug product
is extremely robust to challenging stress conditions that
may occur during patient use of this multidose product
for chronic administration.