title: Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name.
abstract: BACKGROUND
  The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability.
  
  
  METHODS
  Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA.
  
  
  RESULTS
  The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions.
  
  
  CONCLUSIONS
  Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days.
authors.affiliation: Medical Laboratory, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Dewulf
authors.affiliation: Medical Laboratory, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Galanti
authors.affiliation: Medical Laboratory, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Godet
authors.affiliation: Department of Pharmacy, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gillet
authors.affiliation: Scientific Support Unit, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Jamart
authors.affiliation: Department of Pharmacy, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium; Drug Stability Research Group, CHU Dinant Godinne|UCL Namur, 1, avenue Thérasse, 5530 Yvoir, Belgium. Electronic address: jean-daniel.hecq@uclouvain.be.
authors.forename: J-D
authors.initials: JD
authors.lastname: Hecq
mesh_terms: D000212:Acyclovir / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D016568:Drugs, Generic; D005615:Freezing; D007263:Infusions, Parenteral; D019999:Pharmaceutical Solutions; D011090:Polyenes; D012965:Sodium Chloride
chemical_list: D000998:Antiviral Agents; D016568:Drugs, Generic; D019999:Pharmaceutical Solutions; D011090:Polyenes; D012965:Sodium Chloride; C035051:PL 732; D000212:Acyclovir
keywords: Acyclovir infusion; Centralized intravenous additives services; Chromatographie liquide à haute performance; Décongélation par micro-ondes; High-performance liquid chromatography; Long-term stability; Microwave freeze-thaw treatment; Perfusion d’acyclovir; Stabilité à long terme; Unité centrale de reconstitution d’injectables