title: Investigation of the stabilizer elimination during the washing step of charged PLGA microparticles utilizing a novel HPLC-UV-ELSD method.
abstract: Quantification of stabilizer content in microparticles and other products is of great importance for formulation development, drug product quality control as well as for reproducible manufacturing. A fast and sensitive HPLC method with evaporative light scattering detection (ELSD) capable of detecting docusate sodium (DOSS), poly (lactic-co-glycolic acid) (PLGA; Resomer RG 503 H) and R-1,2-dioleoyloxy-3-trimethylammonium-propane (DOTAP) in a single run was successfully developed. In contrast to previously described methods, hydrolysis of PLGA as pretreatment is not necessary, thereby enabling accurate quantification of stabilizer next to the intact matrix polymer. This method was used to investigate the impact of washing procedures of polymeric microparticles manufactured either with anionic stabilizer DOSS or with cationic stabilizer DOTAP. High amounts of DOSS were detected in the washing water. This finding was consistent with the result that no DOSS could be detected in the washed and dried microparticles (<limit of detection). In contrast, DOTAP was hardly measurable in the washing water during all washing cycles. However, DOTAP could be quantified in dried particles. The ratio of DOTAP to dry particle mass was approximately 1:10. This is most probably due to the different polymer surfactant interactions (e.g. charge) and the different hydrophilicity of the stabilizers used.
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany; Department Research Pharmaceutics and Drug Product Development, Merck Serono, Frankfurter Straße 250, 64293 Darmstadt, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Riehl
authors.affiliation: Department Research Pharmaceutics and Drug Product Development, Merck Serono, Frankfurter Straße 250, 64293 Darmstadt, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Harms
authors.affiliation: Department Research Pharmaceutics and Drug Product Development, Merck Serono, Frankfurter Straße 250, 64293 Darmstadt, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hanefeld
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany. Electronic address: maeder@pharmazie.uni-halle.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004143:Dioctyl Sulfosuccinic Acid / Q000032:analysis* / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000032:analysis* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D019344:Lactic Acid / Q000032:analysis* / Q000737:chemistry*; D008027:Light; D010316:Particle Size; D011100:Polyglycolic Acid / Q000032:analysis* / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000644:Quaternary Ammonium Compounds / Q000032:analysis* / Q000737:chemistry; D012542:Scattering, Radiation; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D005229:Fatty Acids, Monounsaturated; D000644:Quaternary Ammonium Compounds; D014867:Water; D004143:Dioctyl Sulfosuccinic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: DOSS; DOTAP; ELSD; Evaporative light scattering; HPLC; Microparticles; PLGA; Quantification; Vaccination