Sildenafil citrate is a white to off-white crystalline powder with a solubility profile dependent on pH.
In the solid state, sildenafil citrate is considered to be extremely stable as demonstrated by data
derived from forced degradation studies. It is stable at 90°C in an inert atmosphere. Significant
degradation occurs only under strong oxidising conditions. Some degradation also occurs under
exposure to strong light.
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The active substance tested, in solid state and in dissolution, under accelerated conditions, show that
sildenafil citrate is stable. Stability studies carried out up to 1 year indicate no significant differences
in appearance and no formation of degradation products, and support the proposed re-test period of
2 years for the active substance in double polyethylene bags inside a fibre drum.
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The tablets are manufactured using a conventional tablet formulation, conventional pharmaceutical
equipment and processes. Development of the formulation and the manufacturing processes (roller
compaction, compression and film-coating) are well described. Compatibility studies demonstrated
that sildenafil citrate was stable with all the tablet excipients except magnesium stearate, which causes
degradation with sildenafil in binary mixtures under stress conditions. However, further stability
studies showed no degradation and magnesium stearate was subsequently selected as lubricant.
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Stability
For the finished product stored in the proposed packaging materials, long-term stability studies have
been carried out at different temperatures and conditions (25ºC/60%RH, 30ºC/60%RH, 40ºC/75%RH)
on batches resulting from Brooklyn (clear coated) up to 9 months, from Amboise (clear coated) up to
6 months and up to 12 months (non clear coated). Based on the resulting data, a 2-years shelf life is
acceptable when the product is stored below 30ºC.
In summary, sildenafil film-coated tablets 25, 50 and 100 mg are conventionally formulated and
manufactured using standard pharmaceutical technology. The chemical-pharmaceutical dossier is well
documented and guarantees the quality of the active substance and the finished product with regard to
uniform efficacy and safety. The specifications set are suitable. The company was however requested
to provide, within the agreed timeframe, batch analysis data generated from full-scale production
batches, and additional supportive stability data to confirm the 2-year shelf-life. The data provided
substantiate the stability of the finished product over a maximum of 5 years.
