E-DRUG: Insulin stability (cont'd)

[Kirsten Myhr <myhr@online.no>]

E-drug: Insulin stability (cont'd)
---------------------------------------------

I enter this debate rather late, but thought the following might still be
of interest, even if it mainly relates to room temp. of 25 degrees C,
and not to tropical conditions (which still need to be studied I think!).
Most studies have been done on Lilly's insulin, but they should be
applicable to all manufacturers' products. It is quoted from Trissel LA.
Handbook on injectable drugs 8th Ed. 1994. For those interested in the
references (in brackets), and without access to the book, get in touch
with me.

"The older acidic form of regular insulin (Lilly) required refrigeration
at 2 to 8 degrees C. At 25 degrees C, intact vials were stable for
several months (413). One study found approx. 5% loss of biological
potency after about 10 months at 25 degrees C (907). The newer
neutral formulation is much more stable at room temp. At 25 degrees C
it is stable for 24 to 30 months (414), although Lilly has recommended
a maximum of 30 days (1433). (NB This is also the recommendation in
Scandinavian datasheets from all three manufacturers: 30 days in room
temp.) One study found approx. 5% loss of biological potency after
about 36 months at 25 degrees C. At 37 degrees C, a 5% loss occurred
in about 5 months (907). Storage of neutral regular insulin under
refrigeration is still recommended (2), but it should not be frozen (4).
Freezing of insulin products may alter the protein structure,
decreasing potency (559). Gregory et al evaluated factors that increase
the formation rate of insulin transformation products (such as
deamidated insulin, covalent dimers, and higher oligamers) in beef and
human insulin products during six months of storage. HPLC analysis
showed a low rate of transformation products appearance at 4 degrees
C. Higher temperatures, as might occur when insulin is carried in a
shirt pocket or car glove compartment, accelerated this production
(esp. for human insulin) and also fibril formation. Exposure to light
increased the dimer and higher oligamer content. According to these
authors, insulin should not be exposed to direct sunlight or subjected
to vibration or extremes of temperature (1633)."

The chapter is longer, but I've left out studies on stability in
syringes.

E-druggers, be aware that Medline is almost useless when searching
for stability of drugs or other pharmaceutical issues, as very few
pharmaceutical journals are (or at least used to be) indexed.

Regards,

Ms Kirsten Myhr, MScPharm, MPH
Bygdoy Alle 58B
0265 Oslo
Norway

Tel: +47 22 56 05 85 (h)
Fax: +47 22 24 90 17 (w) Tel: +47 22 24 88 55 (w)
E-mail: myhr@online.no
or (w): kirsten.myhr@helsetilsynet.dep.telemax.no
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