Improved Stability of Treprostinil Sodium with Proper Vial Puncture Technique and Adapter Use

Abstract

Background: Treprostinil sodium has an expiration date of 14 days following initial vial puncture. Objective: To extend the expiration date of treprostinil sodium after initial vial entry and determine its stability after daily versus every 3-day vial entry. Stability and compatibility of treprostinil sodium with a Clave connector device was assessed. Methods: An initial study considered treprostinil vials punctured daily without regard to proper vial puncture technique. A second study considered treprostinil sodium vials punctured every 3 days with proper technique. Vials in these studies were stored in a stability chamber at 25 °C and 60% relative humidity up to 30 days. Treprostinil stability was assessed with a Clave connector adapter up to 84 days with the vials inverted. Vials were analyzed for treprostinil and m-cresol content, pH, appearance, particulate matter, and sterility. Results: Initial data indicated 14 days as the expiration date after initial vial entry and daily vial puncture. The parameter influencing stability was particulate matter, which was significantly reduced with proper vial puncture technique and vial entry every 3 days. Particulate matter counts remained low up to 84 days using a Clave adaptor and withdrawal every 7 days. Other stability parameters were acceptable throughout the stability study. Conclusions: These data indicate that the number of vial entries influenced treprostinil stability rather than time after initial vial entry. Two methods were identified to extend the expiration date of treprostinil sodium after initial vial puncture: proper vial puncture technique and use of a Clave adapter to withdraw the vial contents.