Abstract:

Aluminum hydroxide adjuvant exhibits a poorly crystalline boehmite (PCB) structure, which demonstrates instability during prolonged storage. In the present study, we systematically investigated the quality alterations of the adjuvant stored at room temperature by analyzing its crystal structure, particle size distribution, electron microscopic characteristics, pH, isoelectric point (pI), and adsorption capacity. These assessments aimed to ensure the effectiveness and safety of vaccine production. Three batches of adjuvants were stored at room temperature for 15 months, and their changes were monitored using X-ray diffraction patterns, transmission electron microscopy (TEM), pH measurements, pI determination, and adsorption capacity analysis. X-ray diffraction revealed that the crystalline phases of aluminum hydroxide initially exhibited a PCB structure, which became progressively more ordered during storage. Notably, after 12 months, a new diffraction peak emerged at 18.2° 2θ, with its intensity increasing over time. This corresponded to the formation of highly crystalline gibbsite and bayerite, which compromised the stability of the adjuvant. Furthermore, the pH and pI values decreased during storage, reflecting a decline in the chemical stability of the adjuvant. Comprising nanoparticles with a mean diameter of 130 nm, the adjuvant maintained a high surface area and excellent adsorption capacity. The adsorption rate at 8 mg BSA/mg Al³⁺ consistently exceeded 97%, with no statistically significant differences observed between the adsorption capacities at 1 and 15 months (P > 0.05). This indicated that the nanoparticle aluminum hydroxide adjuvant sustained high adsorption efficiency throughout the storage period, underscoring its reliability as a vaccine adsorbent. However, in the later stages of storage, the emergence of highly crystalline gibbsite and bayerite, coupled with declines in pH and pI, negatively impacted the adjuvant’s stability. Based on these findings, we recommended that aluminum hydroxide adjuvants should not be stored at room temperature for longer than 12 months to preserve their quality and efficacy.

Key words: Nanoparticles, Aluminum hydroxide adjuvant, X-ray diffraction pattern, Poorly crystalline boehmite, Isoelectric point, Transmission electron microscopy, Adsorption capacity