| Florfenicol, which belongs to chloramphenicol, is a kind of veterinary antibacterial drug. Florfenicol is outstanding because of its specialities such as excellent safety and absorption performance, distributing ability in vivo, wide antimicrobial spectrum and high efficiency. However its poor solubility, long time of reaching the blood plasma concentration peak and low bioavailability reduces the treatment effect. In our study, on the basis of pharmaceutics and hot-melt extrusion technology, FF solid dispersion was prepared using inexpensive and efficient materials. Then new-shaped FF powder with high efficiency, quick release, improved biological utilization, reduced production costs was obtained.We established two methods of determining the concentration of FF, using the UV and HPLC to determine the content of drugs in vitro and vivo respectively, and both of them showed the excellent repeatability and stability. In the two methods, accessories showed no interference oe the determination, resulting in accurate and reliable determination of the FF content. We studied the melting point of the material and accessories of FF, active pharmaceutical ingredients, melting point, solubility and dissolution. We tested the effect of high temperature, high humidity as well as strong illumination on the stability of the active pharmaceutical ingredients.According to the preliminary survey of single factor experiment, we confirmed the orthogonal test factors and levels, with the cumulative dissolution in 10 min as the evaluation index, we carried out the orthogonal test using the hot melt extrusion technology. We studied the influence of Temperature, rotational speed, the proportion of PEG6000 /SE-6 on the SD dissolution. The results showed that the proportion of PEG6000 /SE-6 is the main influence factors of SD, as long as the temperature is higher than the melting point of PEG6000, and speed showed little influence. Finally the optimal prescription and optimum process is determined.The nature of the FF solid dispersion prepared through optimal prescription, optimum technological preparation was characterized by DSC and IR, SD. The results showed that the characteristic peak of FF didn’t appear in the SD, indicating the forming of SD. The experiment which determines the content of FF of the SD showed that the FF was uniformly dispersed, with stable content value. The results of solubility experiment showed that the solubility of FF increased by about 1.5 times, and the bulk drug dissolution of SD was 6 times higher. The experiments of influence factors show that high temperature and high humidity had larger influence on SD, so it should be kept at low temperature in dry environment.By the preliminary preparation of FF powder, we found that the starch interfered the efficiency of drug dissolution, so the adding of magnesium stearate as dispersant and lubricant was considered.Through the test results of different levels of magnesium stearate, we found that FF with 0.9% magnesium stearate showed good dissolution and release performance. According to the result of the experiments we carried out to examine the uniformity, dry weightlessness, content uniformity, angle of repose and bulk density of FF powder, the requirement was met. The experiments of influence factors showed that high temperature and high humidity had larger influence on powder, so it should be kept at low temperature in dry environment.Through the way of lavage, the pharmacokinetics in vivo of rats of API suspension liquid and powder mixed suspension were analyzed using DAS2.0 software.The experimental results showed that the test time of FF powder is shorter on T(max), quick release effect of the new powder is observed, the AUC of FF powder increased by 11.88 % comparing to the bulk drug.In summary, we prepared a kind of new, efficient, safe and inexpensive FF powder,helping to maximize the benefits of veterinary drug manufacturers and farmers. |
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