Abstract
The aim of the current study was to investigate the ability of a fixed-angle routine photon correlation spectrometer (PCS) to resolve bimodal size distributions. The focus was on dispersions consisting of a majority of smaller and a minority of bigger particles. Monodisperse latex beads of sizes from 21 to 269 nm were measured first as single-size dispersions and then with various binary blends. For single-size dispersions, the mean diameters obtained were as indicated by the manufacturer, except for 21- and 34-nm particles, which were somewhat smaller. PCS analysis of blends of 21+102-nm and 34+102-nm particles resulted in bimodal distributions with particle diameters of the 2 peaks in the expected magnitude down to critical blending ratios of 0.002% and 0.08% of bigger particles, respectively. At these ratios, PCS results became inconsistent, and an increased number of monomodal results and/or high residuals were seen. For 21+102-nm blends, at even smaller ratios (0.001%), more consistent results were obtained again with predominantly monomodal distributions in the size range of the smaller particles (ie, the bigger particles were neglected). PCS analysis of blends of 21+269-nm particles yielded bimodal distributions with diameters within the expected magnitude as long as the content of bigger particles did not exceed 0.005%. Above this ratio, predominantly monomodal results with mean diameters in the magnitude of the bigger particles were obtained (ie, the smaller particles were neglected). In conclusion, a routine PCS instrument can resolve bimodal size distributions of colloidal dispersions only at certain ratios of the 2 subpopulations. Both low and high ratios lead to 1 of the 2 subpopulations being neglected.
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References
Goll J, Carlson FD, Barenholz Y, Litman BJ, Thompson TE. Photon correlation spectroscopic study of the size distribution of phopholipid vesicles. Biophys J. 1982;38:7–13.
Particle Sizing Systems, Inc. Stability Analysis of Mostly-Submicron Dispersions by Simultaneous Combination of DLS and SPOS. Santa Barbara, CA: Particle Sizing Systems Inc. Application Note 157.
O Neal D, Harrip P, Dragicevic G, Rae D, Best JD. A comparison of LDL size determination using gradient gel electrophoresis and light scattering methods. J Lipid Res. 1998;39:2086–2090.
Koster VS, Kuks PFM, Lange R, Talsma H. Particle size in parenteral fat emulsion, what are the true limitations? Int J Pharm. 1995;134:235–238.
Daniels CA, Etter AA. Latex particle size analysis by the Coulter Nano-sizer: response to mixtures of sizes, outsize particles and comparison with other methods. Powder Technol. 1982;34(1):113–119.
Liu D, Huang L. Size homogeneity of a liposome preparation is crucial for liposome biodistribution in vivo. J Liposome Res. 1992;2:57–66.
NICOMP Model 380 [user manual]. Santa Barbara, CA: Particle Sizing Systems, Inc; 1997.
Cintre M, Cambon S, Leclerc D, Dodds J. Sizing synthetic mixtures of latex and various colloidal suspensions by photon correlation spectrometry. Anal Chem. 1985;58(1):86–90.
Technical Committee (ISO). Particle Size Analysis-Photon Correlation Spectroscopy. Geneva, Switzerland: International Organization for Standardization; 1996.
Duke SD, Brown RE, Layendecker EB. Calibration of spherical particles by light scattering. [technical note, revised 1/3/2000, http://www.dukescientific.com/pdfs/tech/Tn00202.pdf, originally published in]. Particulate Sci Technol. 1989;7:223–228.
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Frantzen, C.B., Ingebrigtsen, L., Skar, M. et al. Assessing the accuracy of routine photon correlation spectroscopy analysis of heterogeneous size distributions. AAPS PharmSciTech 4, 36 (2003). https://doi.org/10.1208/pt040336
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DOI: https://doi.org/10.1208/pt040336