title: Solubility and Stability of Baclofen 3 mg/mL Intrathecal Formulation and Its Compatibility With Implantable Programmable Intrathecal Infusion Systems.
abstract: BACKGROUND
  Commercial baclofen formulations used with infusion pumps are available at therapeutic concentrations of 0.5-2.0 mg/mL. However, patients who receive higher daily doses of baclofen may benefit from products with greater baclofen concentrations since their refill frequency would be reduced (up to a maximum of 180 days). We evaluated baclofen solubility, baclofen 3 mg/mL intrathecal (IT) formulation stability, and chemical and physical compatibility with Medtronic SynchroMed®II and Codman Medstream®programmable IT infusion pumps.
  
  
  METHODS
  For solubility evaluations, baclofen powder was dissolved into isotonic saline and tested at 5°C, 25°C, and 40°C. To demonstrate drug product stability, both physical and chemical stability attributes of baclofen 3 mg/mL in prefilled syringes were evaluated over 36 months with storage at 25°C. For a simulated in-use stability (compatibility) study, a 3 mg/mL baclofen IT formulation was placed in SynchroMed II and Codman Medstream pumps at 37ºC for study durations, and evaluated at different flow rates. Pump effluent was collected at various times and analyzed by high-performance liquid chromatography for baclofen content. On completion of the in-use stability study, pumps exposed to baclofen 3 mg/mL were dissected and visually evaluated for signs of deterioration.
  
  
  RESULTS
  Baclofen solubility was found to be 3.2 mg/mL at 5°C, 3.6 mg/mL at 25°C, and 3.9 mg/mL at 40°C. During the 36-month stability study of prefilled syringes stored at 25°C, baclofen content remained unchanged and no precipitation was observed. The simulated in-use pump study performed at 37ºC showed that a baclofen 3 mg/mL IT formulation was stable at different flow rates and throughout different expected residence times for both pump models. Components from both pumps exhibited no noticeable deterioration after exposure to the 3 mg/mL formulation.
  
  
  CONCLUSIONS
  Baclofen 3 mg/mL IT formulation was stable during long-term storage at 25°C and remained stable under conditions matching those encountered in clinical practice (37°C).
authors: Parenteral Delivery Systems R&D, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Baohua
authors: B
authors: Yue
authors: Parenteral Delivery Systems R&D, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Ron
authors: R
authors: Brendel
authors: Parenteral Delivery Systems R&D, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Amelia
authors: A
authors: Lukitsch
authors: Medical Combination Products, Winter Haven, FL, USA.
authors: Thomas
authors: T
authors: Prentice
authors: Parenteral Delivery Systems R&D, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors: Brian
authors: B
authors: Doty
mesh_terms: D001418:Baclofen / Q000008:administration & dosage / Q000737:chemistry* / Q000592:standards*; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage / Q000592:standards; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000592:standards*; D007278:Injections, Spinal / Q000379:methods / Q000592:standards; D009125:Muscle Relaxants, Central / Q000737:chemistry* / Q000592:standards*; D012995:Solubility
chemical_list: D009125:Muscle Relaxants, Central; D001418:Baclofen
keywords: Baclofen; concentration; intrathecal; solubility; stability