Characterization of TLR4 Agonist Effects on Alhydrogel® Sedimentation: A Novel Application of Laser Scattering Optical Profiling

Aluminum salt formulations such as Alhydrogel® have been used for decades as effective and safe vaccine adjuvants. Aluminum salts have a high adsorptive capacity for vaccine antigens and other immunomodulatory molecules such as Toll-like receptor (TLR) agonists. However, the characterization of some Alhydrogel®-adsorbed TLR agonists is challenging, requiring destructive analysis, complex instrumentation, and/or desorption method development. In this report, we characterize the effects of an Alhydrogel®-adsorbed synthetic Toll-like receptor 4 (TLR4) agonist on aluminum salt sedimentation behavior using laser scattering optical profiling. This method facilitates the detection of the effects on aluminum salt sedimentation behavior of low amounts of adsorbed TLR4 agonist (<30 μM) with a minimum of sample preparation and analysis time by collecting light transmission simultaneously from the complete vertical profile of the sample. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4357-4364, 2012