title: Impact of sertraline salt form on the oxidative stability in powder blends.
abstract: Oxidation of active pharmaceutical ingredients is a common chemical degradation process occurring in solid dosage forms. The aim of this study was to investigate the tendency of various sertraline salts to oxidize in powder blends containing a basic additive. A different extent of conversion of each salt to the free base was observed to occur in the presence of the basic additive, consistent with their respective pHmax values. Sertraline was found to undergo oxidation as the unioinized form, in both solution and powder blends that incorporated an oxidizing agent. In contrast, the ionized form of sertraline remained stable in both cases. Three sertraline salts undergoing a significant extent of conversion from salt to free form in the presence of tribasic sodium phosphate were found to oxidize extensively while sertraline benzoate which had a considerably lower extent of free base formation was more resistant to oxidation. The oxidative degradants were produced through oxidation at the amine functional group of sertraline which is where sertraline is ionized as the salt form. The link between oxidation tendency and the ionization state of sertraline in powder mixtures has thus been demonstrated in this study.
authors: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA; Allergan Inc., Irvine, CA, USA.
authors: Yi-Ling
authors: YL
authors: Hsieh
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA.
authors: Weili
authors: W
authors: Yu
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA; Takeda, Cambridge, MA, USA.
authors: Yanqiao
authors: Y
authors: Xiang
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA.
authors: Weitao
authors: W
authors: Pan
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA; FreeThink Technologies, Inc. East Lyme, CT, USA.
authors: Kenneth C
authors: KC
authors: Waterman
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA; Allergan Inc., Irvine, CA, USA.
authors: Evgenyi Y
authors: EY
authors: Shalaev
authors: Pfizer Inc, Pharmaceutical Development, Groton, CT, USA.
authors: Sheri L
authors: SL
authors: Shamblin
authors: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA. Electronic address: lstaylor@purdue.edu.
authors: Lynne S
authors: LS
authors: Taylor
mesh_terms: D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D011208:Powders; D012492:Salts; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry*; D020280:Sertraline / Q000737:chemistry*; D012996:Solutions
chemical_list: D005079:Excipients; D011208:Powders; D012492:Salts; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D012996:Solutions
keywords: Acid base reaction; Excipients; Ionization state; Oxidation; Solid state stability; pH(max)