Comparison And Effects Of Dissolution And Antibacterial Activity In Vitro Of Enrofloxacin Treated In Different Ways

For insoluble drugs, poor solubility in water can result in low dissolution rate, andthus often have the problem of bioavailability. Meanwhile, the poor aqueous solubilitywill limit the development of pharmaceutical dosage forms, resulting in a singlepharmaceutical dosage form, and even affecting the practical application of drugs. Thus,enhancing their water solubility is an important issue to be considered in thepharmaceutical formulations. The oral medication is often susceptive to diseasedindividuals, but many drugs have different degrees of bitterness, and thus affect the oraladaptability. Enrofloxacin is an effective one of fluoroquinolones, showing very goodbactericidal effects on various types of bacterial infections in animals, it has beenwidely used in the veterinary clinic, but it has very poor water solubility and also abitter taste. Considering that two aspects, technologies of cyclodextrin inclusion, soliddispersion, ion exchange resin formulation and enteric coating technique wereemployed to enrofloxacin, the resulting products were characterized and evaluated bydifferent ways. In this study, the following works were included:①Preparation of different enrofloxacin-products: by appropriate selection of theconditions, the following enrofloxacin-products were prepared for the experimentalinvestigation: molar ratio1:1enrofloxacin/sulfobutylether-β-cyclodextrin inclusioncomplexes (including binary inclusion complexes and ternary inclusion complexes at30°C and75°C), enrofloxacin solid dispersions (including enrofloxacin/PEG1:9soliddispersions, enrofloxacin/PVP K301:9solid dispersions and enrofloxacin/PVP K30/of ethyl cellulose1:8:1solid dispersions), enrofloxacin resin1:1complexes andenrofloxacin enteric coated particles (coating weight was15,20,25%, respectively).②Characterization of different enrofloxacin-products: phase solubility method,DSC-TGA, X-ray powder diffraction and infrared spectroscopy were used tocharacterize different enrofloxacin-products. The results showed thatenrofloxacin/SBE7-β-CD inclusion complexes formed in a molar ratio of1:1and thusincreased the water solubility of enrofloxacin; in the solid dispersions, there was acertain interaction between enrofloxacin and PVP K30as well as EC, namely hydrogenbonds. Enrofloxacin was highly dispersed and existed in amorphous state in the PVPK30or PVP K30/EC1:8mixture, crystalline enrofloxacin still existed in PEG6000,and no significant interaction was found between them; In enrofloxacin resin1:2 complexes, enrofloxacin existed in amorphous state, highly dispersed in the resin toform a complex; crystalline enrofloxacin still existed in enteric-coated granules, but thethermal behavior changed, especially the positions of the endothermic peak andexothermic peak.③In vitro dissolution test: Paddle method in the veterinary pharmacopoeia (2010edition) was applied to measure the dissolution profiles of enrofloxacin-products andenrofloxacin. The results showed that enrofloxacin-cyclodextrin inclusion complexes,enrofloxacin solid dispersions and enrofloxacin-resin complexes all could significantlyimprove the dissolution rate and dissolution amount of enrofloxacin in pH6.8phosphatebuffer, but there was no significant difference in pH1hydrochloric acid solution.Ethylcellulose adding to the solid dispersion could retard the drug dissolution;Compared with enrofloxacin, enrofloxacin enteric-coated granules could reduce thedissolution rate both in the two dissolution mediums, but the dissolution rate anddissolution amount in pH6.8phosphate buffer were significantly greater than those inpH1hydrochloric acid solution, wherein granules with20%coating weight achieved thebest coating effect with relatively small coating weight.④Bitter taste evaluation: A single-blind method was used, the results showed thatthe enrofloxacin-cyclodextrin inclusion complexes and solid dispersions wereunable to mask the bitter taste of enrofloxacin and even enhanced their bitterness, whilethe adding of ethylcellulose suggested a taste-masking way by reducing the dissolutionof the drug; enrofloxacin resin1:2complexes and enteric-coated granules with20%coating weight showed good taste-masking effects so that tasters coudn’t feel bitterness.⑤In vitro antibacterial test: Oxford cup method was used, the results showed thatthere was no significance between the antibacterial effects of enrofloxacin bulk drugsand enrofloxacin-products. The antibacterial effects depended on the drug concentration,which was related to solubility and in vitro dissolution. In the same time, there was apositive correlation between the solubility/dissolution rate and antibacterialeffects.However, only when the solubility and dissolution amount reached a certainvalue would the antibacterial effects change.