Pharmaceutical Technology, Sanofi Pasteur, USA.
Eur J Pharm Biopharm. 2013 Oct;85(2):272-8. doi: 10.1016/j.ejpb.2013.04.016. Epub 2013 May 11.
Formaldehyde has been used in the inactivation of a number of viral and bacterial toxins used in vaccines. In some cases, a small amount of formaldehyde may be necessary in order to prevent reversion back to the toxic state during storage. When a lyophilized preparation is required, care must be taken to ensure that formaldehyde is not lost during the process in order to ensure safety of the product. A design of experiments (DOEs) approach was taken to devise a stable, lyophilized, vaccine formulation. A formaldehyde-inactivated bacterial toxin was used as a model antigen. Entrapment of formaldehyde in an amorphous matrix and/or interactions with amorphous components was found to be required for complete recovery of formaldehyde during lyophilization. In formulations consisting of sucrose and citrate, formaldehyde could be recovered across a wide range of excipient concentrations. Stability of the antigen was dependent on formaldehyde concentration, with antigen stability decreasing with increasing formaldehyde concentration. This is in contrast to the risk of reversion which increases with decreasing concentrations of formaldehyde. Finally, variations in temperatures during annealing, primary drying, and secondary drying had no impact on formaldehyde recovery.
甲醛已被用于灭活疫苗中使用的多种病毒和细菌毒素。在某些情况下，为了防止储存过程中回复到有毒状态，可能需要少量的甲醛。当需要冻干制剂时，必须小心确保在该过程中不会损失甲醛，以确保产品的安全性。采用实验设计（DOE）方法来设计稳定的冻干疫苗制剂。甲醛灭活的细菌毒素被用作模型抗原。发现甲醛被包埋在无定形基质中和/或与无定形成分相互作用对于在冻干过程中完全回收甲醛是必需的。在由蔗糖和柠檬酸盐组成的制剂中，可以在广泛的赋形剂浓度范围内回收甲醛。抗原的稳定性取决于甲醛浓度，随着甲醛浓度的增加，抗原稳定性降低。这与随着甲醛浓度降低而增加的回复风险形成对比。最后，退火、一次干燥和二次干燥过程中温度的变化对甲醛的回收没有影响。
