PP-003 Production and stability of a ready-to-use hydroxocobalamin solution for paediatric parenteral use

Abstract

Background A paediatric patient in our hospital suffers from a rare, hereditary transcobalamin II deficiency resulting in an intracellular vitamin B12 deficiency. Treatment consists of massive parenteral intake of vitamin B12. Parenteral vitamin B12 solution, suitable for children under 3 years of age, is not commercially available in our country. Purpose The aim was to produce a preservative-free, sterile hydroxocobalamin (vitamin B12) solution at a concentration of 10 mg/2 ml for intramuscular use and to develop an analytical method of indicating the stability in order to determine the shelf life of the solution. Material and methods The entire manufacturing process took place under aseptic conditions. Hydroxocobalamin hydrochloride was dissolved in NaCl 0.9% to give a concentration of 10 mg/2ml. The pH value was adjusted to 4.3–4.5 using hydrochloric acid. The solution was 0.2 µm filtered and finally, 2.4 ml of solution was aseptically filled into sterilised brown glass vials. The filter integrity was tested using the bubble point method. The vials were kept in the refrigerator. Alternatively, the solution was autoclaved at 121°C for 15 min and assessed by high performance liquid chromatography (HPLC) for degradation products. Results The autoclaved solution contained degradation products and the hydroxocobalamin content had decreased by 20%. In contrast, the sterile filtered solution showed no degradation products and no loss in the hydroxocobalamin content was observed after storage for 24 months at 2–8°C. The solution was stable when stored for one month at room temperature and even exposure to 56°C for 2 days did not cause the product to degrade. Conclusion We produced a hydroxocobalamin solution for intramuscular use with a shelf life of at least 24 months if refrigerated. The treatment of our patient with this solution, administered as an intramuscular injection once a week, has been extremely successful for more than 3 years. References and/or acknowledgements No conflict of interest.