Long-term physicochemical stability of acyclovir 5 mg/mL solution stored in polypropylene bags as a simulated hospital stock preparation.

Abstract

To investigate the long-term chemical and physical stability of 5-mg/mL acyclovir solution in polypropylene bags stored at 5°C ± 3°C for 2 months in order to determine the feasibility of batch production by a centralized intravenous additive service. Eight empty 100-mL polypropylene bags (bags A) and 8 empty 250-mL bags (bags B) were respectively filled with 60 mL and 200 mL of 5-mg/mL acyclovir and 0.9% sodium chloride injection (NaCl) under aseptic conditions through a semiautomated manufacturing process and vacuum packed before storage at 5°C ± 3°C. Four bags A and 4 bags B were tested for chemical stability via a stability-indicating high-performance liquid chromatography (HPLC) method immediately after preparation (time 0) and after 7, 14, 21, 28, 35, 42, and 63 days. Samples for microbiological assay were collected on days 0 and 63 from 4 bags A and 4 bags B immediately after breaking the vacuum. Osmolality, pH, and physical stability were assessed by visual examination, Subvisible particle counting was performed on 6 additional bags (3 each of bags A and B). Mean percentage loss of acyclovir relative to the mean experimental concentration at time 0 was below 5% over the 63-day study period.. No significant differences of pH, no change in color and no precipitate were observed during the study. Subvisible particle counts were compliant with European Pharmacopoeia requirements. Acyclovir solutions remained sterile over the 63 days of the study. Extemporaneously prepared acyclovir 5 mg/mL solutions in 0.9% NaCl stored in polypropylene bags were chemically and physically stable over 63 days when stored at 5°C ± 3°C.