title: Formulation of a liquid ovine Fab-based antivenom for the treatment of envenomation by the Nigerian carpet viper (Echis ocellatus).
abstract: Most antivenoms are required for use in tropical or sub-tropical countries where temperatures may be high and refrigerated storage unavailable or unreliable. Although freeze-dried products can be expected to have maximal storage stability, many antivenoms are manufactured in liquid form to lower their cost and ease their use. We developed a liquid formulation of an existing freeze-dried antivenom against the carpet viper (Echis ocellatus) for use in Nigeria. When Fab fragments, prepared from antisera raised in sheep, were exposed to pH between 3.0 and 8.0, time and temperature dependent precipitation of some populations of the Fab product occurred over the range 4.5-7.0. Formulation of the Fab fragments in acetate buffer (20 mM) at pH 4.0 provided a clear, colourless, particle-free and stable product which retained neutralising potency for at least one year at 4 degrees C and room temperature. An accelerated study indicated stability for at least 4 weeks at 37 degrees C which may be considered equivalent to four years at 4 degrees C. The presence of sugars (sorbitol at 20 g/l or mannitol at 50 g/l) or sodium chloride (153 mM) had no effect in stabilising Fab at high temperature (37 degrees C) and, in agreement with the prediction of these accelerated studies, no beneficial effect of mannitol was found in real-time studies after one year.
mesh_terms: D000818:Animals; D000997:Antivenins / Q000008:administration & dosage / Q000737:chemistry*; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000627:therapeutic use; D008353:Mannitol / Q000737:chemistry; D051379:Mice; D011310:Preservatives, Pharmaceutical / Q000737:chemistry; D012756:Sheep; D012909:Snake Bites / Q000628:therapy*; D013012:Sorbitol / Q000737:chemistry; D014757:Viper Venoms / Q000037:antagonists & inhibitors*; D017819:Viperidae
chemical_list: D000997:Antivenins; D002021:Buffers; D007140:Immunoglobulin Fab Fragments; D011310:Preservatives, Pharmaceutical; D014757:Viper Venoms; D008353:Mannitol; D013012:Sorbitol