title: Solution stability of Captisol-stabilized melphalan (Evomela) versus Propylene glycol-based melphalan hydrochloride injection.
abstract: OBJECTIVE
  The objective of this study was to compare the stability of recently approved Captisol-stabilized propylene glycol-free melphalan injection (Evomela™) against currently marketed propylene glycol-based melphalan injection. The products were compared as reconstituted solutions in vials as well as admixture solutions prepared from normal saline in infusion bags.
  
  
  METHODS
  Evomela and propylene glycol-based melphalan injection were reconstituted in normal saline and organic custom diluent, respectively, according to their package insert instructions. The reconstituted solutions were diluted in normal saline to obtain drug admixture solutions at specific drug concentrations. Stability of the solutions was studied at room temperature by assay of melphalan and determination of melphalan-related impurities.
  
  
  RESULTS
  Results show that based on the increase in total impurities in propylene glycol-based melphalan injection at 0.45 mg/mL, Evomela admixture solutions are about 5, 9, 15 and 29 times more stable at concentrations of 0.45, 1.0, 2.0 and 5.0 mg/mL, respectively. Results confirmed that reconstituted Evomela solution can be stored in the vial for up to 1 h at RT or for up to 24 h at refrigerated temperature (2-8 °C) with no significant degradation. After storage in the vial, it remains stable for an additional 3-29 h after preparation of admixture solution in infusion bags at concentrations of 0.25-5.0 mg/mL, respectively. In addition, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan was bacteriostatic through 72 h storage at 2-8 °C.
  
  
  CONCLUSIONS
  Formulation of melphalan with Captisol technology significantly improved stability compared to melphalan hydrochloride reconstituted with propylene-glycol based diluents.
authors.affiliation: a Department of Pharmaceutical Operations, Spectrum Pharmaceuticals Inc. , Irvine , CA.
authors.forename: Ramsharan
authors.initials: R
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutical Operations, Spectrum Pharmaceuticals Inc. , Irvine , CA.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: a Department of Pharmaceutical Operations, Spectrum Pharmaceuticals Inc. , Irvine , CA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Miller
authors.affiliation: a Department of Pharmaceutical Operations, Spectrum Pharmaceuticals Inc. , Irvine , CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bergren
authors.affiliation: a Department of Pharmaceutical Operations, Spectrum Pharmaceuticals Inc. , Irvine , CA.
authors.forename: Rangan
authors.initials: R
authors.lastname: Mallik
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000032:analysis / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control; D004355:Drug Stability; D005079:Excipients / Q000032:analysis / Q000737:chemistry*; D007267:Injections; D008558:Melphalan / Q000032:analysis / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000737:chemistry; D019946:Propylene Glycol / Q000032:analysis / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000032:analysis / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005079:Excipients; D019999:Pharmaceutical Solutions; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D019946:Propylene Glycol; D008558:Melphalan
keywords: Alkeran; Captisol-enabled; Captisol-stabilized; Evomela; admixture; in-use; melphalan; propylene glycol; reconstitution; stability