title: Stability and characterization of perphenazine aerosols generated using the capillary aerosol generator.
abstract: Perphenazine (a potent antiemetic) was aerosolized using capillary aerosol generator to generate respirable condensation aerosols from drug in propylene glycol (PG) solutions, by pumping the liquids through a heated capillary tube. The study characterized the stability of perphenazine during and following aerosol generation. The stability-indicating HPLC method (C-8 column with a mobile phase of 52% 0.01 M pH 3.0 acetate buffer+48% acetonitrile) also enabled the study of perphenazine stability in solution under acidic, basic, oxidizing and photolysing conditions. An LC-MS (ESI+) method was used to characterize the degradation products. Perphenazine was found to be stable in acidic and basic conditions, while perphenazine sulfoxide was the major product formed in dilute peroxide solutions. Two photo-degradation products were formed in PG that were tentatively identified by LC-MS; one of these was synthesized and confirmed to be 2-[4-(3-phenothiazin-10-yl-propyl)-piperazino]-ethanol. Both photolysis products showed that aromatic dechlorination had occurred and one appeared to also result from interaction with the solvent. Within an aerosolization energy window of 84-95 J, fine particle aerosols were generated from perphenazine PG formulations with no significant degradation. Small amounts of degradation products were produced in all samples during aerosolization at elevated (non-optimal) energies. These were largely consistent with those seen to result from oxidation and photolysis in solution, showing that oxidation and dehalogenation appeared to be the main degradation pathways followed when the CAG system was overheated.
authors.affiliation: Aerosol Research Group, Department of Pharmaceutics, Virginia Commonwealth University, Box 980533, 410 North 12th Street, Richmond, VA 23298, USA.
authors.forename: Xihao
authors.initials: X
authors.lastname: Li
authors.forename: Frank E
authors.initials: FE
authors.lastname: Blondino
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
authors.forename: William H
authors.initials: WH
authors.lastname: Soine
authors.forename: Peter R
authors.initials: PR
authors.lastname: Byron
mesh_terms: D000336:Aerosols; D000932:Antiemetics / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D006358:Hot Temperature; D006861:Hydrogen Peroxide; D006863:Hydrogen-Ion Concentration; D008027:Light; D013058:Mass Spectrometry; D009330:Nebulizers and Vaporizers; D010084:Oxidation-Reduction; D010316:Particle Size; D010546:Perphenazine / Q000032:analysis / Q000737:chemistry*; D019946:Propylene Glycol; D015203:Reproducibility of Results; D012996:Solutions; D013997:Time Factors
chemical_list: D000336:Aerosols; D000932:Antiemetics; D012996:Solutions; D019946:Propylene Glycol; D006861:Hydrogen Peroxide; D010546:Perphenazine