Studies On Sustainded-Release Pellets Of Ofloxacin

Ofloxacin,the third generation Fluoquinolone antimicrobial agent , has showed excellent antibacterial activity against gram negative and gram negative bacteria in vitro and in vivo.It is well absorbed when given orally,and moreover, it has a wide ditribution as well as a high absolute bioavailability.But along with the widely using in clinic practice,many side effect occurrence were reported frequently ,hence,a safer and more effective agent are indispensable to suferer . It was reported that Ofloxacin exhibits minimal inhibitory concentrations (MIC's) of <1mg/Ml,which suggest the possibility of preparation the sustained-released pellets. The purpose of the present study was designed to develop a kind of Ofloxacin sustained -release pellets which would decrease adverse effects and focus on urinary tract infection and which would be more convenient for urinary tract infection patients to use.HPLC method was utilized to determine the ofloxacin content in pellets, UV method for assaying release of ofloxacin sustained- release capsules. HPLC and UV methods were developed to analyze the intestinal absorption of ofloxacin in rats. The HPLC method was established to monitor the plasma and urine level in vivo.The preformulation results showed that ofloxacin's solubility in self-made gastric juice is 40.7mg/ml and sparingly soluble in various physiological pH fluids(>4.5)and the octanol/water partition coefficients increase with pH rising in various physiological pH fluids exhibiting pH-dependent characteristicThe absorption sites and the absorption kinetics were studied from various intestinal segments ligation using in situ perfusion method in rats. The research demonstrated that ofloxacin was poorly absorbed in intestine in general and mostly absorbed in the upper and middle small intestine. When the concentration was raised from 2.0 to 10.0μg·mL^-1, the uptake of ofloxacin increased and no saturation phenomenon occurred, whereas the absorption rate constant kept at a same level. The absorption of ofloxacin was influenced by pH value between pH 5.5 and pH 7.4. There were significant differences among the absorption rate constants in the varied intestinal segments. The absorption rate constants (h^-1) of duodenum, jejunum and ileum per 10cm were 0.0544 h^-1, 0.0368 h^-1,...