title: Aerosol based detectors for the investigation of phospholipid hydrolysis in a pharmaceutical suspension formulation.
abstract: A high performance liquid chromatography (HPLC) method was developed to quantify free fatty acids (FFA) in a pharmaceutical suspension formulated with phospholipids as stabilizing agents. Specifically, a suspension of crystalline itraconazole microparticles stabilized with Lipoid E80 was used as a model system to study the physicochemical stability of an aqueous, phospholipid-based suspension for injection. The hydrolysis of the phospholipids during storage at elevated temperatures (40 degrees C) necessitated the development of a suitable HPLC method for the determination of free fatty acid content in the suspension samples. HPLC methods using two types of aerosol detectors were investigated for the above purpose. Reversed-phase separation coupled with either an evaporative light scattering detector (ELSD) or a Corona(Plus) charged aerosol detector (CAD) was used. A comparison of the methods indicated that the CAD method provided better sensitivity, precision, recovery, and linearity for the parameters evaluated. As a result, this method was chosen for the stability study of itraconazole suspension and has been incorporated in subsequent formulation studies.
authors.affiliation: Global Research & Development, Baxter Healthcare, Round Lake, IL 60073, USA. lakshmy_nair@baxter.com
authors.forename: Lakshmy M
authors.initials: LM
authors.lastname: Nair
authors.forename: Jane O
authors.initials: JO
authors.lastname: Werling
mesh_terms: D000336:Aerosols / Q000032:analysis / Q000737:chemistry*; D000935:Antifungal Agents / Q000032:analysis / Q000737:chemistry; D002138:Calibration; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D004355:Drug Stability; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D017408:Guidelines as Topic; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D017964:Itraconazole / Q000032:analysis / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013535:Suspensions; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D000935:Antifungal Agents; D005230:Fatty Acids, Nonesterified; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D013535:Suspensions; D014867:Water; D017964:Itraconazole