title: Monitoring the chemical and physical stability for tromethamine excipient in a lipid based formulation by HPLC coupled with ELSD.
abstract: Tromethamine, a UV-transparent amine base excipient, was used in the liquid phase of a self-emulsifying drug delivery system-soft gelatin capsule (SEDDS-SGC) formulation as an emulsification agent and to improve solubilization of the active drug. The level of this excipient was found to be decreasing in aged and stressed drug product capsules. The decrease could potentially affect oral bioavailability of the drug; should the amount of solubilizer decrease enough to lead to precipitation of the active drug from the formulation. Therefore, further investigation was warranted. HPLC coupled with evaporative light scattering detection (ELSD) was used to monitor the physical and chemical stability of tromethamine in the SEDDS-SGC formulation. Confirmation of the tromethamine interaction products was done by LC-MS.
authors.affiliation: Analytical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA. Electronic address: dr.shirley.rodriguez@outlook.com.
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Rodríguez
authors.affiliation: Analytical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Fenghe
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Analytical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mulcey
authors.affiliation: Analytical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Weigandt
authors.affiliation: Analytical Development US, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Toby
authors.initials: T
authors.lastname: Tamblyn
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004075:Diglycerides / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D008027:Light; D015394:Molecular Structure; D050178:Monoglycerides / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D012542:Scattering, Radiation; D012995:Solubility; D014325:Tromethamine / Q000737:chemistry*
chemical_list: C000608598:Capmul MCM; D004075:Diglycerides; D005079:Excipients; D050178:Monoglycerides; D004364:Pharmaceutical Preparations; D014325:Tromethamine
keywords: Evaporative light scattering detection (ELSD); HPLC; LC–MS; Lipid formulation; Self-emulsifying drug delivery systems (SEDDS); Soft gelatin capsules (SGC); Tris; Tromethamine; Tromethamol