title: Stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride and polyolefin bags.
abstract: OBJECTIVE
  The stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride (PVC) and polyolefin bags under varying conditions was evaluated.
  
  
  METHODS
  Triplicate solutions of midazolam hydrochloride 1-mg/mL were prepared in polyolefin and PVC i.v. bags by diluting midazolam hydrochloride injection 5 mg/mL with 5% dextrose injection. Bags were then stored under refrigeration (3-4 °C), exposed to light at room temperature (20-25 °C), or protected from light in amber bags at room temperature. Samples were taken immediately after preparation (day 0) and on days 1, 2, 3, 6, 13, 20, and 27 for analysis with a stability-indicating high-performance liquid chromatography assay in order to determine solution concentration. Stability was defined as retention of at least 90% of the initial drug concentration. The pH of each solution was also measured weekly. Sterility of the i.v. bags was determined at the end of the study by microbiological testing with culture in growth media. Differences in concentrations under the various storage conditions and bags used were analyzed using analysis of variance.
  
  
  RESULTS
  All solutions retained over 98% of the initial midazolam hydrochloride concentration, with no statistically significant (p ≥ 0.05) change in concentration over the four-week period. Stability was not affected by temperature, exposure to light, or bag type. The pH of all solutions remained between 3.2 and 3.4 throughout the study. Sterility after 28 days was retained.
  
  
  CONCLUSIONS
  Midazolam hydrochloride 1-mg/mL solutions diluted in 5% dextrose injection remained stable over 27 days in both polyolefin and PVC i.v. bags, regardless of storage condition.
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, USA. karlage@pharmacy.arizona.edu
authors.forename: Kelly
authors.initials: K
authors.lastname: Karlage
authors.forename: Zachary
authors.initials: Z
authors.lastname: Earhart
authors.forename: Kelly
authors.initials: K
authors.lastname: Green-Boesen
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005947:Glucose / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006993:Hypnotics and Sedatives / Q000737:chemistry*; D007262:Infusions, Intravenous; D008874:Midazolam / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D011090:Polyenes / Q000737:chemistry*; D011143:Polyvinyl Chloride / Q000737:chemistry*; D012034:Refrigeration; D013696:Temperature; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D019999:Pharmaceutical Solutions; D011090:Polyenes; C035051:PL 732; D011143:Polyvinyl Chloride; D005947:Glucose; D008874:Midazolam