| Tiamulin fumarate, is a dedicated pleuromutilins animals antibiotics, is one of the world’s top ten veterinary antibiotics, It is rapidly absorbed by animals and are widely distributed in their bodies. Then,the blood concentration is high,and the residual is low. Tiamulin fumarate in recent years has been widely used to control porcine proliferative ileitis and has received better results. Enteric microcapsules make use of enteric polymer material as the capsule material for preparing microcapsules, then the stability of the drug in the stomach can be improved, so as to achieve the purpose of the intestinal targeted drug delivery, and thus intestinal enteric microcapsules treatment tract disease is important. In order to improve Tiamulin fumarate porcine proliferative ileitis the treatment of intestinal diseases. In this study, an acrylic resin II as capsule material, the use of a liquid preparation of enteric Tiamulin Fumarate dried microcapsules, and its related properties, and its pharmacokinetic characteristics of rabbits were studied. d.Since strongest ultraviolet absorption wavelength of tiamulin fumarate is 208nm. We chose HPLC to determine encapsulation efficiency, drug loading and in vitro release of enteric microcapsules which contain Tiamulin fumarate. HPLC conditions: Column:KromasilC18 column (4.6mm × 250mm,5μm), mobile phase:acetonitrile: 1% phosphoric acid=5:95(v/v), UV wavelength 208nm, flow rate:1.0mL/min, column temperature:30 ℃,injection volume:lOuL.The regression equation is: A=12023C+350002(R2=0.9995,n=7). The linear range was5-320μg/mL. The relative standard deviation ofinter-day precision was 1.3% and 1.85%, standard deviation was 0.286 and 1.853, respectively. The recovery rate was 98.81%±1.98%.The data within the requirements in the drug content determination.Preparing microcapsules by single factor experiment.The orthogonal get the best preparation of microcapsules. The optimal preparation conditions were follows: Eudragit L 1.0g, Span-80 3.0g and Glyceryl monostea rate was 1.0g and the speed of stir was 400r/min. We get the complete spherical.Tiamulin fumarate enteric microcapsule, The average particle size was 240±27μm. It have complete smooth appearance and good fluidity. The mean encapsulation and mean loading rate was 85.09%±1.99% and 20.57%±1.03%, respectively. In vitro dissolution experiments in different media showed that tiamulin fumarate enteric microcapsule scumulative release was 8.32% at pH2 artificial gastric in 2h. Cumulative release at pH7.6 artificial intestinal fluid was 82.23%, which has obvious enteric properties, and compared with tiamulin fumarate, it have stong sustained release. The stability experiments show that microencapsulated tiamulin fumarate resistance against strong light, high heat and high humidity are improved.Tiamulin fumarate enteric microcapsules and tiamulin fumarate bulk drugs for healthy rabbits. Compare pharmacokinetic trials to the pharmacokinetic characteristics of the drug and microcapsules. The HPLC concentration limit determination was 0.15μg/mL.Research the measurement resultswith DAS2.0 pharmacokinetics procedures. Determine the optimal AV model to analyze the pharmacokinetic parameters with SPSS (17.0).The results follows:group of Tiamulin fumarate:T1/2Ka:(1.3 52±0.396) h; T1/2a:(1.969±0.201) h; T1/2β. (20.911±3.874) h; Tmax:(4±0.000) h; Cmax:(9.022±2.15) mg/L; AUC(0-∞):(109.910±24.408) mg/L*h; MRT(0-∞):(24.372±9.957) h,the fitting equation: C=150,295e-0.403t+1.885e-0.028t-152.18e-0.513t。 group of Tiamulin fumarate enteric microcapsules:T1/2Ka:(1.932±0.449) h; T1/2α:(25.035±1.34) h; T1/2β: (52.659±13.275)h; Tmax:(12±0.000)h; Cmax:(7.315±0.992) mg/L; AUC(0-∞)为(177.655±44.777) mg/L*h; MRT(0-∞):(22.962±1.591) h, the fitting equatio:C=95.68e-0.138t+2.318e-0.097t-97.998e-0.359t.It is concluded that tiamulin fumarate microcapsules compared with tiamulin fumarate original drug that group of microencapsulated tiamulin fumarate could sustained release and significantly improves the bioavailability of the drug.This experiment successfully prepared tiamulin fumarate enteric microcapsules, this process is simple, controllable quality. Drug quality assessment, in vitro release experiments and pharmacokinetic experiments showed that tiamulin fumarate enteric microcapsules with targeted, slow release, increased bioavailability characteristics for tiamulin fumarate for treatment porcine proliferative ileitis foundation and provides a new way of thinking for intestinal veterinary research targeted drug delivery system. |
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