Klein J, Ushio M, Burrell L S, Wenslow B, Hem S L
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J Pharm Sci. 2000 Mar;89(3):311-21. doi: 10.1002/(SICI)1520-6017(200003)89:3<311::AID-JPS3>3.0.CO;2-8.
The present study explores the use of (27)Al magic-angle-spinning (MAS) NMR for the characterization of aluminum hydroxyphosphate adjuvants. Adjuvants were prepared by two different methods: batch-precipitation and precipitation at constant pH, using a wide range of different conditions. The adjuvant compositions showed no evident stoichiometric restrictions and varied as a function of the precipitation conditions. All the aluminum hydroxyphosphate adjuvants were found by (27)Al MAS NMR to contain both tetrahedrally and octahedrally coordinated aluminum. The octahedral form was always predominant. The chemical shifts corresponding to octahedral aluminum were at values intermediate between that of aluminum hydroxide (9 ppm) and those of phosphate-containing aluminum minerals such as variscite (-9 ppm) and varied with the phosphate content of the adjuvant. This was true even for adjuvants precipitated above pH 6 indicating that the phosphate is incorporated into the bulk solid phase contrary to predictions in the literature. Aside from the presence of tetrahedral and octahedral aluminum, there was no evidence in any of the adjuvants of distinct, structurally defined phases indicating that the adjuvants are not mixtures of distinct phases which differ significantly in the number of phosphorus atoms in the next-nearest-neighbor (NNN) position to aluminum.
本研究探索了使用（27）Al 魔角旋转（MAS）核磁共振（NMR）来表征羟基磷酸铝佐剂。通过两种不同方法制备佐剂：分批沉淀法和恒pH沉淀法，采用了广泛的不同条件。佐剂组成未显示出明显的化学计量限制，且随沉淀条件而变化。通过（27）Al MAS NMR发现，所有羟基磷酸铝佐剂均含有四面体配位铝和八面体配位铝。八面体形式始终占主导。与八面体铝对应的化学位移值介于氢氧化铝（9 ppm）和含磷铝矿物（如磷铝石，-9 ppm）的化学位移值之间，并随佐剂的磷酸盐含量而变化。即使对于在pH 6以上沉淀的佐剂也是如此，这表明磷酸盐与文献中的预测相反，被掺入到块状固相之中。除了存在四面体铝和八面体铝之外，在任何佐剂中均未发现存在明确的、结构确定的相的证据，这表明佐剂并非是在与铝的次近邻（NNN）位置的磷原子数量上有显著差异的不同相的混合物。
