Huyghebaert N, De Beer J, Vervaet C, Remon J P
Laboratory of Pharmaceutical Technology, Ghent University, Gent, Belgium.
J Clin Pharm Ther. 2007 Oct;32(5):489-96. doi: 10.1111/j.1365-2710.2007.00855.x.
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.
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.
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%.
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.
囊性纤维化（CF）患者存在脂溶性维生素（A、D、E和K）吸收不良的问题。这些维生素有水分散型（A、D3和E）或水溶性剂型（K3），由于CF患者无法吸收油基产品，所以这类剂型更受青睐。本研究的目的是确定这些原料在打开原包装后的稳定性，并开发一种质量、稳定性和口感均可接受的复方制剂，使其能够灵活调整剂量，且适合儿童和老年人服用。
原料打开原包装后，在8℃和室温（RT）下储存8个月。从冷水溶性基质（维生素A醋酸酯、D3和E）中提取维生素后，采用经过验证的高效液相色谱法评估稳定性，或采用分光光度法（维生素K3）评估稳定性。将这些原料与适当等级的乳糖混合（维生素A和D3用乳糖80m；维生素E用乳糖90m；维生素K3用乳糖极细粉），并装入硬明胶胶囊中。测定装量和含量均匀度，并在8℃和室温下储存2个月后评估胶囊中维生素的稳定性。
所有原料在打开原包装后于8℃和室温下储存8个月期间均表现出良好的稳定性（初始含量的>95%）。复方制剂符合欧洲药典对装量和含量均匀度的要求，可在8℃或室温下储存2个月，同时保持维生素含量在90%至110%之间。
由于这些脂溶性维生素在比利时市场上没有商业供应，复方制剂是向CF患者预防性给药这些维生素的一种有价值的替代方案，即一种稳定的制剂，口感可接受，允许灵活调整剂量，且适合儿童和老年人服用。
