The Research Of Levofloxacin Sustained-release Granules Used For Veterinary Drugs

Bacterial infection is a kind of disease which brings about serious damage to the growth of livestock, poultry. According to the report, the world's poultry bacterial infection rates is as high as 50% ~ 70%, and the outbreak of bacterial infections in poultry mortality reached 20% ~ 30%, leading to bacterial infection in the poultry industry in our country every year about 300 million, the number of chicken death caused direct economic losses of about 3 billion yuan, the indirect loss of about 10 billion yuan. Bacterial infection is one of the most important diseases in the intensive poultry industry. The main method of prevention and cure is the immune control and drug therapy, immune control can prevent the disease, but when the outbreak of bacterial infection mainly rely on drug treatment, according to incomplete statistics, the consumption of world's antimicrobials drug is more than $300 million. Therefore, the research of high efficiency, low toxicity, broad antimicrobial spectrum new dosage forms and new formulations is become the significant means of resistant bacterial infection drug. Enrofloxacin, difloxacin, danofloxacin, ofloxacin, and other types of anti-bacterial infections drug has been used in veterinary clinical. Among them, fluoroquinolones drugs have advantages of low toxicity, broad antimicrobial spectrum, low raw material prices,so it is very widely used in the veterinary clinicmainly for the treatment of respiratory tract caused by susceptible strains, urinary tract infections, and can promote animal growing weight, and improve feed conversion rate.Levofloxacin is ofloxacin's active isomer L- optically,it's antibacterial activity is twice of racemic form, 8 to 128 times of dextral body, It was the first successful listing fluoroquinolones which has good anti-pneumococcal active, It was respectively listing in Japan and the USA in 1993 and 1997, In clinical,this medicine have been used for the treatment of patients more than 300 million, rarely resistance. It has strong antibacterial activity against the majority of Enterobacteriaceae bacteria, it also have certain antibacterial activity against streptococcus pyogenes, streptococcus pneumoniae, staphylococcus aureus, mycoplasma pneumoniae chlamydia,therefore it has been widely applied in clinic. But levofloxacin's half-life is six hours, relatively short.In veterinary clinical, frequent administration will increase poultry's stress response and probability of adverse reaction resulting from plasma concentration fluctuation. However,sustained released formulation can solve this problem.In this paper, I take a systematic pharmaceutical research on highly efficient broad-spectrum Antibacterial drugs levofloxacin sustained-release granules, the mainly works are as follows:(1)Overviewed Levofloxacin's structure, physical and chemical properties, action mechanism, and introduced the new preparation technology of sustained-release formulation, in the hope of sustained-release preparation technology to reduce the release of levofloxacin, decrease times of taking medicine and reduce the stress reaction of poultry. On this basis, according to the physical and chemical properties of levofloxacin API and excipients, quality standard, choosing different dosage of skeleton material, fillers, adhesives and lubricants to prepare levofloxacin sustained-release, determined in 0.5, 1, 2, 4, 6, 9 and 12 h cumulative release degree of the drug, with 2, 6, 12 h cumulative release as examining index, preliminarily determine the prescription by levofloxacin, wax skeleton material stearic acid, hydrophilic matrix HPMC, starch, adhesive PVP, lubricant talcum powder filler composition, preparation method is wet legal system grain.(2) investigation by single factor and orthogonal design experimental methods examines the best prescription of levofloxacin sustained-release granules.The optimal prescription(1000g): levofloxacin: 250g; Stearic acid: 170g; HPMC: 500g; Starch: 30g; PVP: 50g; talcum powder: proper amount, by using the dissolution method,the sustained-release formulation was investigated, and the drug release mechanism was studied. Eventually, proving that Higuchi equation is the best fitting model, and the levofloxacin sutained-release particles release is the synergistic effect of diffusion and bulk erosion.(3)In order to control the quality of the product effectively, a systematic quality standard reaserch were taken to levofloxacin sustained-release granules, including shape, identification, assay and release test and so on, the results show that the preparation process is stable, good and consistent quality. The prepared quality standards(draft) could control products quality effectively.(4)The stability studies of levofloxacin sustained-release granules were investigated, the results showed that levofloxacin sustained-release granules with simulation of commercially available packaging is stability in the condition of temperature(40±2)?, relative humidity(75±5)% for six months or temperature is(25±2)?, relative humidity(60±5)% for 12 months.