Kinetic measurements of the hydrolytic degradation of cefixime: effect of Captisol complexation and water-soluble polymers.
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.
Mallick
Subrata
S
Formulation Development and Drug Delivery Systems, Department of Pharmaceutics, College of Pharmaceutical Sciences, Berhampur, Mohuda-760002, Orissa, India. smallickin@yahoo.co.in
Mondal
Arijit
A
Sannigrahi
Santanu
S
D020682:Cefixime / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D011108:Polymers; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D020682:Cefixime