Compounding of vitamin A, D3, E and K3 supplements for cystic fibrosis patients:: formulation and stability study

Background and objective: Cystic fibrosis (CF) patients suffer from malabsorption of fat-soluble vitamins (A, D, E and K). These vitamins are available as water-dispersible (A, D-3 and E) or water-soluble grades (K-3), which is favoured in CF patients as they fail to absorb oil-based products. The objective of this study was to determine stability of these raw materials after opening the original package and to develop a compounded formulation of acceptable quality, stability and taste, allowing flexible dose adaptation and being appropriate for administration to children and elderly people. Methods: The raw materials were stored after opening their original package for 8 months at 8 degrees C and room temperature (RT). Stability was assessed using a validated HPLC method after extraction of the vitamin from the cold water-soluble matrix (vitamin A acetate, D-3 and E) or using a spectrophotometrical method (vitamin K-3). These materials were mixed with an appropriate lactose grade (lactose 80 M for vitamins A and D-3; lactose 90 M for vitamin E, lactose very fine powder for vitamin K-3) and filled in hard gelatin capsules. Mass and content uniformity were determined and stability of the vitamins in the capsules was assessed after 2 months storage at 8 degrees C and RT. Results: All raw materials showed good stability during storage in the opened original package for 8 months storage at 8 degrees C as well as RT (> 95% of the initial content). The compounded formulations complied with the requirements of the European Pharmacopoeia for mass and content uniformity and can be stored for 2 months at 8 degrees C or RT while maintaining the vitamin content between 90% and 110%. Conclusions: As these fat-soluble vitamins are not commercially available on the Belgian market, compounded formulations are a valuable alternative for prophylactic administration of these vitamins to CF patients, i.e. a stable formulation, having an acceptable taste, allowing flexible dose adaptation and being appropriate for administration to children and elderly people.