It is notoriously difficult to maintain a reliable cold chain for goods travelling to, or being stored in, rural communities in developing countries. This has serious implications for the distribution of medicines, vaccines, testing reagents and other substances, often with significant implications for healthcare.
One such substance are antivenoms. Whilst not something the Western world is greatly attuned to, snakebite envenomings are a highly relevant public health problem in areas of Asia, Latin America and Sub-Saharan Africa. The accepted treatment for snakebite envenomings is the parenteral administration of animal-derived liquid formulation antivenoms.
February’s ‘Paper of the Month’ from Herrera et al. uses the FDCS196 freeze-drying stage to investigate the viability of freeze-drying snake antivenoms. Freeze-drying is used to improve the long term stability of many pharmaceutical proteins, and eliminate the need for a continual temperature control. Proteins are stabilised through formulation with sugars and polyols, but until now the use of these compounds in the development of freeze-dried antivenoms has not been documented.
In this paper, whole immunoglobulin G antivenom from equine plasma was formulated with varying concentrations of sorbitol, sucrose or mannitol, and stored for 6 months at 40°C.
The authors said, “The thermal characterization of anti-venoms using freeze-drying microscopy and differential scanning calorimetry is crucial for the development of the freeze-drying process. The Linkam Instrumentation allowed us to know the collapse temperature of different formulations of snake antivenoms and determine which of them were suitable for freeze-drying in term of stability, cost and productivity”.
The formulations were tested for stability and the neutralisation of the lethal effect of Bothrops asper venom. All formulations except antivenoms freeze-dried with mannitol exhibited the same potency, and the 5% sucrose formulation exhibited the best stability.
The results obtained provide valuable information for the production of more stable freeze-dried antivenoms in developing countries, where an adequate cold chain cannot be guaranteed. This could dramatically increase their availability in the areas they are most needed.
Herrera, M., Tattitini Jr, V., Pitombo, RNM., Gutierrez, JM., Borgognoni, C., Vega-Baudrit, J., Solera, F., Cerda, F., Cerda, M., Segura, A., Villalta, M., Vargas, M. and Leon, G. (2014). Freeze-dried snake antivenoms formulated with sorbitol, sucrose or mannitol: Comparison of their stability in an accelerated test. Toxicon 90, pp56-63.
By Frances Coles