Mallick Subrata, Mondal Arijit, Sannigrahi Santanu
Formulation Development and Drug Delivery Systems, Department of Pharmaceutics, College of Pharmaceutical Sciences, Berhampur, Mohuda-760002, Orissa, India.
J Pharm Pharmacol. 2008 Jul;60(7):833-41. doi: 10.1211/jpp.60.7.0004.
We have taken kinetic measurements of the hydrolytic degradation of cefixime, and have studied the effect of Captisol complexation and water-soluble polymers on that degradation. The phase solubility of cefixime in Captisol was determined. Kinetic measurements were carried out as a function of pH and temperature. High-performance liquid chromatography (HPLC) was performed to assay all the samples of phase-solubility analysis and kinetic measurements. Chromatographic separation of the degradation products was also performed by HPLC. FT-IR spectroscopy was used to investigate the presence of any interaction between cefixime and Captisol and soluble polymer. The phase-solubility study showed A(L)-type behaviour. The pH-rate profile of cefixime exhibited a U-shaped profile whilst the degradation of cefixime alone was markedly accelerated with elevated temperature. A strong stabilizing influence of the cefixime-Captisol complexation and hypromellose was observed against aqueous mediated degradation, as compared with povidone and macrogol. The unfavourable effect of povidone and macrogol may have been due to the steric hindrance, which prevented the guest molecule from entering the cyclodextrin cavity, whereas hypromellose did not produce any steric hindrance.
我们已对头孢克肟的水解降解进行了动力学测量，并研究了Captisol络合和水溶性聚合物对该降解的影响。测定了头孢克肟在Captisol中的相溶解度。动力学测量是作为pH和温度的函数进行的。采用高效液相色谱（HPLC）对所有相溶解度分析和动力学测量的样品进行测定。降解产物的色谱分离也通过HPLC进行。利用傅里叶变换红外光谱（FT-IR）研究头孢克肟与Captisol和可溶性聚合物之间是否存在相互作用。相溶解度研究显示为A（L）型行为。头孢克肟的pH-速率曲线呈U形，而单独的头孢克肟降解随温度升高而显著加速。与聚维酮和聚乙二醇相比，观察到头孢克肟-Captisol络合和羟丙甲纤维素对水介导的降解具有很强的稳定作用。聚维酮和聚乙二醇的不利影响可能是由于空间位阻，这阻止了客体分子进入环糊精腔，而羟丙甲纤维素没有产生任何空间位阻。
