Thyagarajapuram Nagarajan, Olsen David, Middaugh C Russell
Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, KS 66049, USA.
J Pharm Sci. 2007 Dec;96(12):3363-78. doi: 10.1002/jps.21022.
Gelatin prepared from animal sources is widely used as a stabilizer in vaccine formulations. The disadvantages associated with their use such as heterogeneity and allerginicity, have led to the development of recombinant human gelatins (rhGs) as a substitute. This study focuses on characterizing the structure and monitoring the physical stability of four molecular weights ( approximately 8.5, 25, 50, and 100 kDa) of rhGs as a function of temperature and pH. The information supplied should be useful in predicting the behavior of rhGs under formulation conditions. A number of spectroscopic techniques were employed in this study. Experimental results indicated that the solution properties of all four rhGs were unpredictable with micro-aggregation observed at various pH values. The 8.5 kDa rhG was found to be in a micro-aggregated state at pH 5 while the 25 kDa rhG was found to be more aggregated at pHs 5, 7, and 8. The properties of these aggregates have been analyzed as a function of temperature. The rhGs were also found to complex with the polyanion heparin through electrostatic and nonelectrostatic interactions. The stability of these complexes has been studied as a function of temperature and pH.
从动物源制备的明胶被广泛用作疫苗制剂中的稳定剂。与其使用相关的缺点，如异质性和过敏性，促使人们开发重组人明胶（rhG）作为替代品。本研究着重于表征四种分子量（约8.5、25、50和100 kDa）的rhG的结构，并监测其随温度和pH值变化的物理稳定性。所提供的信息应有助于预测rhG在制剂条件下的行为。本研究采用了多种光谱技术。实验结果表明，所有四种rhG的溶液性质都不可预测，在不同pH值下均观察到微聚集现象。发现8.5 kDa的rhG在pH 5时处于微聚集状态，而25 kDa的rhG在pH 5、7和8时聚集程度更高。已分析了这些聚集体的性质随温度的变化情况。还发现rhG通过静电和非静电相互作用与多阴离子肝素形成复合物。已研究了这些复合物的稳定性随温度和pH值的变化情况。
