Department of Pharmacy - Drug Sciences, Università degli Studi di Bari Aldo Moro, Bari 70125, Italy.
Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, Bari 70124, Italy.
J Pharm Sci. 2021 Jan;110(1):543-547. doi: 10.1016/j.xphs.2020.10.012. Epub 2020 Oct 13.
The solubility of bortezomib, a boronic acid, in water and normal saline is often misquoted in the literature. Here we confirm that bortezomib equilibrium solubility in water and normal saline is 0.59 ± 0.07 and 0.52 ± 0.11 mg/mL, respectively. The aqueous solubility is significantly enhanced, 1.92 ± 0.14 and 3.40 ± 0.21 mg/mL, respectively, in the presence of 55 mM and 137 mM D-mannitol in normal saline, as in the commercial formulation, Velcade®, after reconstitution. This is due to reversible ester formation between bortezomib and D-mannitol. Based on the pH-solubility profile curve for bortezomib in the absence of added D-mannitol, bortezomib's pKa value is estimated to be 8.8 ± 0.2. Boric acid, glycine and a combination of the two, used in an alternative formulation to that of Velcade® do not enhance the equilibrium aqueous solubility of bortezomib.
硼替佐米（一种硼酸）在水中和生理盐水中的溶解度在文献中常被错误引用。在此，我们证实硼替佐米在水中和生理盐水中的平衡溶解度分别为 0.59 ± 0.07 和 0.52 ± 0.11mg/mL。硼替佐米在生理盐水中的溶解度显著提高，分别为 1.92 ± 0.14 和 3.40 ± 0.21mg/mL，在存在 55mM 和 137mM D-甘露醇的情况下，与商业制剂 Velcade®（硼替佐米复溶后）中的情况相同。这是由于硼替佐米和 D-甘露醇之间形成了可逆的酯。根据硼替佐米在无添加 D-甘露醇的情况下的 pH-溶解度曲线，硼替佐米的 pKa 值估计为 8.8 ± 0.2。硼酸、甘氨酸以及两者的组合，用于替代 Velcade®的制剂并不能提高硼替佐米的平衡水溶解度。
