ABSTRACT
PURPOSE: To compare the chemical stability of Captisol-enabled (CE) melphalan ("CE-melphalan"; Evomela, Acrotech Biopharma LLC) and propylene glycol (PG)-based melphalan ("PG-melphalan"; Alkeran, GlaxoSmithKline) admixtures prepared with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags or reconstituted vials stored at room temperature (RT) and under refrigeration. METHODS: Lyophilized CE-melphalan and generic PG-melphalan were reconstituted to 5 mg/mL with 0.9% sodium chloride injection or manufacturer-supplied diluent, respectively. The reconstituted vials were then diluted to the desired concentrations with 0.9% sodium chloride injection in PVC bags and were stored at RT (23oC) or under refrigeration (4oC). Aliquots were withdrawn from the bags and reconstituted vials of CE-melphalan and PG-melphalan immediately after preparation and at predetermined time intervals. Melphalan concentrations were measured using a validated high-performance liquid chromatography method. RESULTS: CE-melphalan reconstituted in PVC bags at concentrations of 1 and 2 mg/mL was stable for 6 and 24 hours, respectively, at RT and for 8 and 24 hours, respectively, at 4oC. PG-melphalan reconstituted in bags at 1, 1.5, and 2 mg/mL was stable for 1, 2, and 2 hours, respectively, at RT and for 2, 4, and 4 hours, respectively, at 4oC. Reconstituted CE-melphalan vials were stable for 48 hours at both RT and 4oC, whereas PG-melphalan vials were stable for 6 hours at RT but formed precipitate within 2 hours at 4oC. CONCLUSION: CE-melphalan remained stable longer than generic PG-melphalan under the test conditions. CE-melphalan at 2 mg/mL has 24-hour stability at RT and can be used for extended infusion times or may be compounded ahead of time. Reconstituted CE-melphalan vials are stable for 48 hours at both RT and 4oC.
Subject(s)
Melphalan , Refrigeration , Chromatography, High Pressure Liquid , Drug Packaging , Drug Stability , Drug Storage , Humans , Melphalan/chemistry , Polyvinyl Chloride/chemistry , Propylene Glycols , Sodium Chloride/chemistry , Temperature , beta-CyclodextrinsABSTRACT
This review presents the early history, the motivation, the research and some of the backstories behind the discovery and development of sulfobutylether-ß-cyclodextrin as a novel parenterally safe solubilizer and stabilizer. A specific sulfobutylether-ß-cyclodextrin with an average degree of 6.5 sulfobutyl-groups variably substituted on the 2-, 3- and 6-hydroxyls of the seven glucopyranose (dextrose) units of ß-cyclodextrin, is known by its commercial name, Captisol®. Today it is in 13 FDA approved injectables and numerous clinical candidates. It is also an example of a novel product discovered and initially preclinically developed at an academic institution.