| Tilmicosin is a kind of chemical semi-synthetic antibiotics of the macrolide family,used for the treatment of respiratory disease in poultry. This semi-synthetic drug acts asantimicrobials has a broad spectrum of antibacterial activity against gram-negativebacteria and gram-positive bacteria. But poor aqueous solubility of drug give rise todifficulties in the design of pharmaceutical formulation. In order to improve thesolubility and bioavailability, develop more formulations and promote more applicationin clinical, liposome, solid dispersion and enteric-coating techniques have been used toimprove the solubility and antibacterial of tilmicosin. Several different detections wereapplied to analyze each formulation。In this paper，the research contents and results as follows:①First of all, built standard curve of tilmicosin and measuring methods ofencapsulation efficiency of liposome with UV spectrophotometry. Different models ofglucan gels have been used to detect elution curves, recovery rates and encapsulationefficiency of liposome. Nano size and Zeta potential analyzer was used to detect sizeand Zeta potential of liposome from different recipes and preparation methods.Compare encapsulation efficiency、particle diameter and Zeta potential of liposomefrom several preparations in optimized recipe, film method shows the best thanammonium sulfate gradient method，pH gradient method and reverse evaporatingmethod. Encapsulation efficiency of film method is51.28%, while the liposome madeby ammonium sulfate gradient method，pH gradient method and reverse evaporatingmethod are30.06%,41.65%and45.83%respectively. The liposome with the particlediameter of film method, ammonium sulfate gradient method, pH gradient method andreverse evaporating method are103.7nm,78.21nm,81.66nm and248.6nm respectively.The Zeta rotentials are-31.7mV,-19.3mV,-24.1mV and-5.28mV.②Different ratios of tilmicosin solid dispersions were prepared by solventmethod and melting method. DSC-TGA, X-ray diffraction and FTIR were applied todetect these solid dispersions. The results prove that some interaction among tilmicosinand carrier, drug was totally dispersed in carrier.③Tilmicosin enteric coating granules were prepared by different recipes andcoating materials. Three batches of enteric coating granules in different coating weight ratio were prepared, the content of tilmicosin were detected with UVspectrophotometry.④Drug release experiments were applied on liposome prepared by differentmethods. The drug release was accorded with the first-order kinetic equation:ln(100Q)0.2980t4.5087(r2=0.9739) compared with other equations forliposome prepared by film method. Dissolution rate of Enteric coating granules wereapplied in gastric fluid and intestinal fluid to research granule with different coatingweight effect on accumulate dissolution of granule. In two kinds of solid dispersion,dissolution rates of tilmicosin/PEG solid dispersion in different ratios are very fast, at5min absolutely dissolve out,above98%. While the tilmicosin/PVP-EC solid dispersionshows particularly lag of dissolution, but drug dissolution rate reached85%eventually.⑤In Vitro antibacterial test were applied to research pure drug and fiveformulation samples. The results showed that inhibition zones of liposome are a littleless than pure drug, no significant difference between enteric coating granule and puredrug, just a little difference in the sensitivity of different strain. The inhibition oftilmicosin/PEG solid dispersion is the best, because it has a fast dissolution rate andreaches the minimum inhibited concentration very soon. There is a certain sustainedrelease of tilmicosin/PVP/EC solid dispersion, but in a short time tilmicosin coulddissolve out to inhibited bacteria.In Vitro drug release tests and antibacterial tests show that dissolution rates oftilmicosin disposed by three different technologies have been improved in differentdegree, the results of antibacterial test are related to the dissolution rate. |
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