储存温度对纳米氢氧化铝佐剂质量稳定性的影响

doi:10.5246/jcps.2025.10.067

摘要/Abstract

摘要：

氢氧化铝佐剂为弱结晶勃姆石(PCB)结构, 该晶体结构受储存条件的影响。本研究旨在揭示佐剂在不同储存温度条件下晶体结构及常规质量指标变化情况。三批氢氧化铝佐剂分别在2–8 ºC、18–25 ºC和37 ºC下储存6个月。检测佐剂的X-射线衍射、pH值、等电点(pI)、吸附率以及平均粒径。X-射线衍射显示佐剂为勃姆石结构。氢氧化铝佐剂在37 ºC下储存1个月, 佐剂衍射图在18.2 º2θ出现新的衍射峰, 并且峰面积随着储存时间而增加。同时佐剂在37 ºC条件下存放pI和pH值下降最明显, 分别为下降0.78和1.33; 当佐剂在2–8 ºC下储存时, 仅在第6个月时, 在18.2 º2θ出现微弱的衍射峰, 表明晶体结构开始发生变化。且pI和pH的下降最少, 分别为0.43和0.80。佐剂的平均粒径为110–140 nm, 因此佐剂具有高蛋白质吸附率, 约8 mg BSA/mg Al³⁺。在不同温度条件下, 佐剂吸附率差异无统计学意义 (P > 0.05)。纳米氢氧化铝佐剂在整个储存过程中保持较高的吸附能力, 使其成为非凡的疫苗吸附剂。但贮存温度的升高会加速佐剂的老化, 形成高结晶的三水铝石或拜耳石, 不利于佐剂质量稳定性。

关键词: 氢氧化铝佐剂, 弱结晶勃姆石, X-射线衍射, 等电点, 吸附能力, 平均粒径

Abstract:

The aluminum hydroxide adjuvant possesses a poorly crystalline boehmite (PCB) structure, the stability of which is significantly affected by storage conditions. In the present study, we conducted a comprehensive investigation into the structural and quality alterations of aluminum hydroxide adjuvants under varying temperature conditions over time. Three batches of the adjuvant were stored at 2–8 °C, 18–25 °C, and 37 °C, respectively, for 6 months. Key parameters, including X-ray diffraction patterns, pH, isoelectric point (pI), adsorption capacity, and average particle size, were analyzed to assess the impact of storage temperatures. X-ray diffraction analysis confirmed the PCB structure of the aluminum hydroxide adjuvant. Notably, after 1 month of storage at 37 °C, new diffraction peaks emerged at 18.2 °2θ, with their intensity increasing progressively over time. Concurrently, the largest decreases in pI and pH were observed, measuring 0.78 and 1.33, respectively. In contrast, adjuvants stored at 2–8 °C for 6 months exhibited only faint diffraction peaks at 18.2 °2θ, indicating minor structural changes. Under these conditions, the reductions in pI and pH were comparatively smaller, at 0.43 and 0.80, respectively. The average particle size of the adjuvants remained within 110–140 nm across all storage conditions. Additionally, the aluminum hydroxide adjuvant consistently demonstrated a high protein adsorption capacity, approximately 8 mg BSA/mg Al³⁺, with no statistically significant differences in adsorption rates observed among the different temperature conditions (P > 0.05). These findings highlighted the remarkable adsorption efficiency of nanoparticle aluminum hydroxide adjuvants throughout storage, reinforcing their potential as superior vaccine adsorbents. However, elevated storage temperatures were shown to accelerate structural aging, promoting the formation of highly crystalline phases such as gibbsite or bayerite, which could compromise the stability and quality of the adjuvant.

Key words: Aluminum hydroxide adjuvant, Poorly crystalline boehmite, X-ray diffraction, Isoelectric point, Adsorption capacity, Average particle size

Supporting:

杨希飞, 张飞伟. 储存温度对纳米氢氧化铝佐剂质量稳定性的影响[J]. 中国药学(英文版), 2025, 34(10): 911-920.

Xifei Yang, Feiwei Zhang. Effects of storage temperature on the quality stability of nanoparticle aluminum hydroxide adjuvant[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(10): 911-920.

图/表 7

Figure 1. X-ray diffractograms of the three batches of adjuvants (A, B, and C) after being stored at 2–8 °C for 1, 3, and 6 months. The horizontal axis represents the 2θ degree, and the vertical axis indicates the peak intensity.

Figure 2. X-ray diffractograms of the three batches of adjuvants (A, B, and C) after being stored at 18–25 °C for 1, 3, and 6 months. The horizontal axis represents the 2θ degree, and the vertical axis indicates the peak intensity.

Figure 3. X-ray diffractograms of the three batches of adjuvants (A, B, and C) after being stored at 37 °C for 1, 3, and 6 months. The horizontal axis represents the 2θ degree, and the vertical axis indicates the peak intensity.

Table 1. X-ray diffraction peaks area at 18.2 °2θ of the three batches of adjuvants (A, B, and C) after storage at 2–8 °C, 18–25 °C, and 37 °C for 6 months.

Figure 4. The pH (a) and pI (b) of the three batches of adjuvants (A, B, and C) at 1, 3, and 6 months when stored at 37 °C, 18–25 °C, and 2–8 °C. The horizontal axis represents the months, and the vertical axis indicates the pH and pI values.

Figure 5. The adsorption rate of the three batches of aluminum hydroxide adjuvants (A, B, and C) stored at 2–8 °C, 18–25 °C, and 37 °C for 1, 3, and 6 months. The horizontal axis represents the different concentrations of BSA used in the adsorption test, and the vertical axis shows the adsorption rate of aluminum hydroxide.

Figure 6. The average particle size of the three batches of adjuvants (A, B, and C) at 1, 3, and 6 months is presented. The horizontal axis represents the storage time, and the vertical axis indicates the average particle size.

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