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Excipients & Actives for Pharma
No. 26, 2011
STABILITY OF FORMULATED OXYGEN-SENSITIVE ACTIVE INGREDIENTS
Extended stabilization of active ingredients highly sensitive
to oxidation using Kollidon 30 LP
Angelika Maschke, Karl Kolter
INTRODUCTION | Pharmaceutical formulators
regularly require a low peroxide content in
the excipients used to avoid degradation of the
active ingredients (APIs) used. BASF fulfils this
need to the maximum extent with its high-quality
Kollidon grades and the packaging concept
introduced in this ExAct issue (see pages 2-4).
Moreover, the formulation of drugs that are
highly sensitive to oxidation has become an
additional major challenge for formulation scientists.
For this purpose, it is of the utmost importance
to use excipients with an especially
low peroxide content.
Considering the close contact between active
ingredients and excipients during wet granu lation
or direct compression, the peroxide level of the
excipient has a strong impact on the stability
of the API. As a first formulation approach, the
stability of the API in a binder solution allows
the appropriate binder to be identified. The goal
of this study was to investigate the effect of the
peroxide content of povidone on API stability in
solution.
Using Kollidon 30 LP in
the formulation of actives
highly sensitive to
oxidation can significantly
improve drug stability.
Set-up of experiments The effect of Kollidon
30 Low Peroxide in solution on stabilization
against oxidation was investigated using ascorbic
acid and hydrocortisone as model substances.
Povidones of different peroxide content (see
table 1) were used to prepare a 20% aqueous
solution. Ascorbic acid was incorporated at a
0.1% level and hydrocortisone at 0.025%.
For the stability study, the samples were filled
in glass vials incubated with or without argon,
closed with a rubber cap and sealed with a
cramp. The solutions were stored for 3 months at
25°C and 60% relative humidity. The API content
was determined by HPLC.
Results Both drug substances showed higher
stability in solutions prepared with Kollidon 30 LP.
After 1 month in Kollidon 30 LP solution, the
ascorbic acid content was 50% vs. 30% in a
PVP solution with a starting peroxide level of
< 260ppm (Figure 1). A similar stabilization effect
was found for hydrocortisone solutions
(Figure 2).
Povidone
Peroxide content
Kollidon 30 LP Very low < 20 ppm
PVP 30 Low < 260 ppm
PVP 30 Enriched 370 ppm
TABLE 1
Povidone grades used for preparing aqueous acid solutions
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