title: Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens.
abstract: Evaluation of the physical characteristics of vaccines formulated in the presence of adjuvants, such as aluminum salts (Alum), is an important step in the development of vaccines. Depending on the formulation conditions and the associated electrostatic interactions of the adjuvant particles, the vaccine suspension may transition between flocculated and deflocculated states. The impact of practical formulation parameters, including pH, ionic strength, and the presence of model antigens, has been correlated to the sedimentation behavior of aluminum phosphate suspensions. A novel approach for the characterization of suspension properties of Alum has been developed to predict the flocculated state of the system using a sedimentation analysis-based tool (Turbiscan®). Two sedimentation parameters, the settling onset time (Sonset) and the sedimentation volume ratio (SVR) can be determined simultaneously in a single measurement. The results demonstrate the suspension characteristics to be significantly altered by solution conditions (pH and ionic strength) and the charge state of bound antigens. Formulation conditions that promote the flocculated state of the suspension are characterized by faster Sonset and higher SVR, and are generally easy to resuspend. The Turbiscan® method described herein is a useful tool for the characterization of aluminum-containing suspensions and may be adapted for screening and optimization of suspension-based vaccine formulations in general.
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc. Chesterfield Missouri 63017.
authors.forename: Kevin
authors.initials: K
authors.lastname: Muthurania
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc. Chesterfield Missouri 63017. Electronic address: arun.alphonseignatius@pfizer.com.
authors.forename: Arun Alphonse
authors.initials: AA
authors.lastname: Ignatius
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc. Chesterfield Missouri 63017.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc. Chesterfield Missouri 63017.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Williams
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc. Chesterfield Missouri 63017. Electronic address: satoshi.ohtake@pfizer.com.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtake
mesh_terms: D000534:Alum Compounds / Q000737:chemistry; D017607:Aluminum Compounds / Q000737:chemistry*; D000818:Animals; D000941:Antigens / Q000737:chemistry; D002417:Cattle; D005427:Flocculation; D006863:Hydrogen-Ion Concentration; D009113:Muramidase / Q000737:chemistry; D009994:Osmolar Concentration; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D064166:Vaccine Potency; D014612:Vaccines / Q000737:chemistry*
chemical_list: D000534:Alum Compounds; D017607:Aluminum Compounds; D000941:Antigens; D010710:Phosphates; D014612:Vaccines; D012710:Serum Albumin, Bovine; C041524:aluminum sulfate; D009113:Muramidase; C012714:aluminum phosphate
keywords: Alum; formulation; physical characterization; preformulation; sedimentation analysis; sedimentation volume ratio; stabilization; suspension; vaccine adjuvants