Study On The Compatibility Between Butyl Rubber Closures And Ceftriaxone Sodium

Pharmaceutical packaging is very important for the stability of drug, and it can directly influence the quality of the pharmaceutical preparation for human use. The components of unsuitable packaging material could evaporate to be adsorbed by the active ingredients in the pharmaceutical products and sometimes chemical reactions could happen between pharmaceutical products and pharmaceutical packaging after being stored, which will degrade the drug and even cause toxic adverse reactions.Based on the market information, the phenomenon that the clarity of drug solution is not complied with the requirement is evident during storage among some antibiotic powders for injection, such as ceftriaxone sodium for injection, cefazolin sodium for injection, cefotaxime sodium for injection.It is reported that the compatibility between butyl rubber closures and pharmaceutical products could influence the clarity of drug solution. Many researches have been carried out on the compatibility between them in the world. But until now there have hadn't definite conclusions to the problem in China as well as in the world.In this thesis we had conducted a series of experiments to study the compatibility between butyl rubber closures and pharmaceutical preparations to investigate the possible factors that influence the clarity of ceftriaxone sodium solution and found BHT, an antioxidant in rubber closures, could influence the solution clarity. The experiment results could give a very useful suggestion for pharmaceutical companies to select butyl rubber closures.The following experiments have been carried out in this article:1. Investigation of the possible factors to influence the clarity of ceftriaxone sodium solution.2. Analysis of butyl rubber closures using FTIR-ATR, TGA, and GC-MS with headspace method and liquid extraction method.3. In the experiments, BHT was found that it could evaporate from butyl rubber closures to the vial and be adsorbed by ceftriaxone sodium during store period to cause the clarity problem of ceftriaxone sodium. And the main inter-reaction mode between butyl rubber closures and ceftriaxone sodium was verified. By using the multiple regressions method, it showed that the volatiles in butyl rubber closures were the main factor to cause the clarity of ceftriaxone sodium.4. Study on the adsorption kinesics of BHT by ceftriaxone sodium and establish the quantitative method to measure the content of BHT in butyl rubber closures and the contents adsorbed by ceftrixaone sodium for injection.5. Analysis of two unqualified batches of cefotaxime sodium-sulbactam sodium by GC-MS and the results showed that BHT was also the main factor to cause the clarity problem of pharmaceutical products.The adsorption of BHT by some other antibiotics, such as ceftfiaxone sodium, cefazolin sodium, cefotaxime sodium, was also studied and the results showed that different antibiotics made different adsorptive extent.In conclusion, for the first time in China as well as in the world in this thesis, the qualitative and quantitative methods of BHT, the main factor to cause the clarity problem of the injectable ceftriaxone sodium, were established, which can be used by pharmaceutical companies to select suitable butyl rubber closures for their injectable products.Above all, the experiment results in the thesis gave a basis for the study on the compatibility between pharmaceutical compounds and pharmaceutical packaging.