Stability of extemporaneously prepared saquinavir formulations

Aims: The effects of pH and excipients on the stability of saquinavir in extemporaneously prepared suspensions were assessed. The stability of a developed extemporaneously prepared saquinavir suspension was then determined at 5 and 25 °C over 30 days.

Method: Extemporaneous saquinavir 2 mg/mL formulations were prepared from soft gelatin capsule (Fortovase). Four batches of the formulations were buffered at pHs 2, 4, 5 and 7, whereas the other five batches were prepared in Milli-Q water, 0·5% (w/v) citric acid, 0·1% (w/v) sodium ascorbate, 10% (v/v) syrup and in vehicle containing both 0·5% (w/v) citric acid and 0·1% (w/v) sodium ascorbate. The stability of these formulations was tested at 25 °C. A final formulation of saquinavir suspension (60 mg/mL) containing both 10% (v/v) syrup and 0·5% (w/v) citric acid was developed and tested for stability at 5 and 25 °C for up to 30 days using a stability-indicating high-performance liquid chromatographic method.

Results: Saquinavir was most stable at pH 2–4. Formulations containing sodium ascorbate, citric acid and syrup or both citric acid and sodium ascorbate were significantly more stable than the control formulation (saquinavir 2 mg/mL in Milli-Q water).

Conclusion: The pH for optimal stability of saquinavir was around 2–4. Besides pH adjustment, saquinavir could also be stabilized by adding anti-oxidants. The saquinavir 60 mg/mL formulation prepared with about a pH of about 4 was stable at both 5 and 25 °C for at least 30 days.