Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2003 September; 4(3): 62–70.
Published online 2003 June 4. doi:  10.1208/pt040336
PMCID: PMC2750629

Assessing the accuracy of routine photon correlation spectroscopy analysis of heterogeneous size distributions


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.

Keywords: dynamic laser light scattering, quasielastic light scattering, latex colloids, particle size, size analysis

Full Text

The Full Text of this article is available as a PDF (417K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. 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. doi: 10.1016/S0006-3495(82)84524-4. [PubMed] [Cross Ref]
2. 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.
3. 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. [PubMed]
4. 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. doi: 10.1016/0378-5173(95)04409-4. [Cross Ref]
5. 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. doi: 10.1016/0032-5910(83)87039-9. [Cross Ref]
6. Liu D, Huang L. Size homogeneity of a liposome preparation is crucial for liposome biodistribution in vivo. J Liposome Res. 1992;2:57–66. doi: 10.3109/08982109209039901. [Cross Ref]
7. NICOMP Model 380 [user manual]. Santa Barbara, CA: Particle Sizing Systems, Inc; 1997.
8. 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. doi: 10.1021/ac00292a021. [Cross Ref]
9. Particle Size Analysis-Photon Correlation Spectroscopy. Geneva, Switzerland: International Organization for Standardization; 1996.
10. Duke SD, Brown RE, Layendecker EB. Calibration of spherical particles by light scattering. Particulate Sci Technol. 1989;7:223–228. doi: 10.1080/02726358908906540. [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists