Ruiz Llamil, Reyes Nuria, Sotolongo Jorge, Aroche Kethia, Aldana Raymersy, Báez Reynier, Hardy Eugenio
Department of Development and Formulations, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana, Cuba.
PDA J Pharm Sci Technol. 2006 Jan-Feb;60(1):72-8.
In this work, we evaluate the stability of a new freeze-dried and albumin-free formulation of recombinant human IFN alpha 2b (rhIFN-alpha2b) to be used in humans. The freeze-dried, albumin-free formulation was stored at the recommended temperature of 4 degrees C, and under accelerated storage conditions (28 degrees C). The stability of this product was also compared with the stability of a liquid albumin-free formulation of this cytokine. Finally, the stability of the freeze-dried albumin-free formulation was examined after reconstitution and storage at 4 degrees C and room temperature (28 degrees C) for 30 days. Samples were periodically subjected to biological activity assay (antiviral titration), reversed phase high-performance liquid chromatography (RP-HPLC), pyrogens, sterility and enzyme-linked immunosorbent assay (ELISA) testing, abnormal toxicity screening, organoleptic evaluation, and measurement of residual moisture and pH. Accelerated storage (28 degrees C) data for the freeze-dried albumin-free formulation showed biochemical stability of the active ingredient throughout the 6-month study, showing activity between 85 and 125% of its nominal value. RP-HPLC-determined purity showed that rhIFN-alpha2b remained above 95%. Additionally, the formulation was non-pyrogenic, non-toxic, sterile, and organoleptically acceptable. The real-time storage data confirmed the good biochemical long-term (30 months) stability of the freeze-dried formulation of this cytokine. Comparison with the liquid rhIFN-alpha2b albumin-free preparation showed that the freeze-dried albumin-free formulation maintained the stability of the active ingredient better than the liquid preparation. The formulation was also stable after reconstitution and storage at 4 degrees C and 28 degrees C, for 30 days.
在本研究中，我们评估了一种用于人类的新型重组人干扰素α2b（rhIFN-α2b）冻干无白蛋白制剂的稳定性。该冻干无白蛋白制剂在推荐温度4℃以及加速储存条件（28℃）下保存。还将该产品的稳定性与该细胞因子的液体无白蛋白制剂的稳定性进行了比较。最后，对冻干无白蛋白制剂复溶后在4℃和室温（28℃）下储存30天的稳定性进行了检测。定期对样品进行生物活性测定（抗病毒滴定）、反相高效液相色谱（RP-HPLC）、热原、无菌和酶联免疫吸附测定（ELISA）检测、异常毒性筛查、感官评价以及残留水分和pH值的测量。冻干无白蛋白制剂在加速储存（28℃）条件下6个月的研究数据表明，活性成分在整个研究期间具有生化稳定性，活性在其标称值的85%至125%之间。RP-HPLC测定的纯度表明rhIFN-α2b保持在95%以上。此外，该制剂无热原、无毒、无菌且感官上可接受。实时储存数据证实了该细胞因子冻干制剂具有良好的生化长期（30个月）稳定性。与液体rhIFN-α2b无白蛋白制剂相比，冻干无白蛋白制剂比液体制剂能更好地保持活性成分的稳定性。该制剂在复溶后于4℃和28℃下储存30天也具有稳定性。
