Prevention of Crystal Formation during Formulation of Acyclovir Powder for Solution for Infusion

Aims and objectives: The main objective of the present work is to develop acyclovir powder for solution for infusion with clear solution upon half sealing and formation of stable cake after freezing drying programme. During the development, after half sealing stage, a mild turbid color formation in vials was observed followed by crystal formation. This was later investigated due to presence of residual oxygen content in the headspace of the vial and also in freeze drying chamber. Material and method: Aciclovir, sodium hydroxide and cool water for injection was used to prepare solution for injection. Followed by pre-filtration and sterile filtration into colorless vials and semi seal the vials in freeze-drying mode with rubber stoppers. Final freeze-drying programme was performed and cap them with aluminum caps. Results and discussion: Trial 3 showed stable clear solution after few hours. This was due to lower concentration of oxygen in the headspace, which was obtained due to introduction of nitrogen during filling stage. Conclusion: Crystal formation was due to presence of oxygen in the head space, which can be avoided by maintaining oxygen level below 0.5% in headspace volume of vials and also stable formed after changing the freeze drying cycles.