title: Pramlintide injection drug product robustness studies.
abstract: The article examines the effects of temperature excursions and actual dose withdrawal on the quality of pramlintide injection, a multidose liquid parenteral formulation. Studies were designed to demonstrate product robustness under conditions that may occur during patient use. Pramlintide %Purity was determined by two high-performance liquid chromatography (HPLC) methods, a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method. A second RP-HPLC method was used to determine pramlintide potency and the concentration of the m-cresol preservative. Antimicrobial preservative effectiveness testing was per USP and European Pharmacopeia (Ph. Eur.). Short-term stability studies were undertaken to probe the effects of the following conditions: 5 degrees C to 40 degrees C and 5 degrees C to -20 degrees C temperature cycling over 10 days; once daily or four-times daily dose withdrawal over 12 or 42 days; and combined 30 degrees C storage and four-times daily dose withdrawal over 42 days. In all cases, pramlintide %Purity and potency values remained essentially unchanged or unchanged relative to controls. Similarly, product appearance, and m-cresol concentration and preservative effectiveness were not significantly affected by the stress conditions used in the 5 studies. Pramlintide injection drug product is extremely robust to challenging stress conditions that may occur during patient use of this multidose product for chronic administration.
authors.affiliation: Cabrillo Facility of Magellan Laboratories, Inc., 9250 Trade Place, San Diego, CA 92126, USA. rkenley@cabrillolabs.com
authors.forename: R A
authors.initials: RA
authors.lastname: Kenley
authors.forename: F
authors.initials: F
authors.lastname: Bancroft
authors.forename: J
authors.initials: J
authors.lastname: L'Italien
authors.forename: A
authors.initials: A
authors.lastname: Stepanenko
authors.forename: M
authors.initials: M
authors.lastname: Townsend
authors.forename: T
authors.initials: T
authors.lastname: Dixit
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods / Q000706:statistics & numerical data; D007267:Injections; D058228:Islet Amyloid Polypeptide; D011310:Preservatives, Pharmaceutical / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D011310:Preservatives, Pharmaceutical; C105254:pramlintide