Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin.
Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of beta-cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with beta- cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 microg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 microg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with beta-cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.
Bhargava
S
S
Department of Pharmaceutical Sciences, Dr. H.S. Gour University Sagar (M.P.) 470003, India.
Agrawal
G P
GP
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015169:Colony Count, Microbial; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D010403:Penicillin Resistance; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*; D000097627:Cefpodoxime Proxetil
D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000097627:Cefpodoxime Proxetil; C031215:betadex