Melt granulation for Enhanced Dissolution Rate and Antimicrobial activity of Cefpodoxime Proxetil

Abstract

The aim of this work was to improve dissolution rate and antibacterial activity of cefpodoxime proxetil (CP) by Pluronic PE 6800 (Poloxamer 188) as eutectic forming hydrophilic polymer. CP was incorporated in the polymer by melt granulation technique. CP was mixed with melted polymer before addition of Avicel, in absence and presence of HPMC E6, with mixing to provide flowable particles. The formulations were characterized using thermal analysis and Fourier transform infrared spectroscopy (FTIR) in addition to dissolution studies. The antibacterial activity of CP against Proteus mirabilis was also explored. FTIR suggested possible hydrogen bonding between CP and polymers. All formulations improved CP dissolution compared to unprocessed CP. This could be attributed to the formation of eutectic species, as reflected by thermal analysis as new endothermic peak at Tm value of 40°C was detected in thermograms of all tested formulations. Microbiological investigations indicated that the optimized formulation offered advantages over pure CP with reduced minimum inhibitory concentration. Additionally, formulated CP decreased the biofilm formation ability among the tested P. mirabilis clinical isolates relative to unprocessed CP. The study introduced melt granulation of CP with poloxamer 188 as a promising tool for enhanced dissolution and augmented activity against Proteus mirabilis with capacity to minimize the biofilm formation.