title: Determination of surface-bound hydroxypropylcellulose (HPC) on drug particles in colloidal dispersions using size exclusion chromatography: a comparison of ELS and RI detection.
abstract: Evaporative light scattering (ELS) and refractive index (RI) detection methods were evaluated for the determination of surface-bound hydroxypropylcellulose (HPC) on drug particles in colloidal dispersions. Size exclusion chromatography (SEC) was used to separate HPC from other components of the dispersions. The instrumental parameters of the ELS detector were optimized to obtain maximum peak intensity, adequate peak shape and minimal baseline noise by varying the mobile phase flow rate, nebulizer temperature, and evaporation temperature. The chromatographic method was validated using both detectors. The ELS detector response exhibited second order polynomial and linear double logarithmic correlation with concentration over a 10-300% range while the RI response was linear. The double logarithmic correlation simplified the calculation compared to using the polynomial fit, and it provided more accurate results compared to the linear fit approach. Total HPC was obtained by solubilizing all components of the dispersion and analyzing for HPC. Non-bound HPC was obtained by ultracentrifuging the dispersion and analyzing the supernatant for HPC concentration. Analysis for total- and non-bound HPC in a representative colloidal dispersion gave method precisions with R.S.D.s of 2.5 and 2.2% for ELS, and 4.5 and 2.4% for RI (n=4). HPC bound to the surface of the drug particles was determined by difference: % bound HPC=100%-% non-bound HPC. Resultant % bound HPC values ranged from 22.1 to 25.4% of available HPC. Both ELS and RI are satisfactory detection techniques for HPC quantitation and for determination of the proportion of HPC bound to drug colloid particles, and the assay results are comparable.
authors.affiliation: Merck Research Laboratories, Pharmaceutical Analysis and Control, Merck and Co., Inc., WP 14-2E, P.O. Box 4, West Point, PA 19486, USA.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhu
authors.forename: Randal A
authors.initials: RA
authors.lastname: Seburg
authors.forename: Eric W
authors.initials: EW
authors.lastname: Tsai
mesh_terms: D000465:Algorithms; D002482:Cellulose / Q000031:analogs & derivatives* / Q000032:analysis; D002850:Chromatography, Gel; D003102:Colloids; D005079:Excipients / Q000032:analysis; D007202:Indicators and Reagents; D008027:Light; D010316:Particle Size; D012031:Refractometry; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D003102:Colloids; D005079:Excipients; D007202:Indicators and Reagents; D002482:Cellulose; C008079:hydroxypropylcellulose