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.