| As a broad-spectrum antibiotic Doxycycline hyclate is widely used in the veterinary clinic. Because of its instability, oral dosage forms and injection of doxycycline usually have great intimulation.and its storage and application were limited in a certain extent. Microencapsulation could not only enhance pharmacal stability, prolonged drug's release time, but also lessen harm to stomach. Microcapsules can also further be made into other dosage forms for clinical application convenient, such as pulveres, tablet, granules, injection et al.. At present, there has no report about doxycycline hyclate microcapsules at home and abroad.,In this study, biodegradable chitosan was selected as the membrane material and doxycycline hyclate microcapsules were prepared by emulsifying crosslinking method.Characters of doxycycline hyclate-chitosan microcapsules and its pharmacokinetics in health rabbits were evaluated.An RP-HPLC method of higher specialty was used to detect the content and entrapment efficiency. The analysis was performed on a Kromasil Cig (4.6mmx 150mm, Sum) analytical column. The mobile phase was composed of a mixture of 0.05 mol/Lammonium oxalate solution-N.N-dimethyl fomamide-0.2 mol/Lammonium monohydric phosphate solution-methanol (53:33:4:10) at a flow rate of 0.8mL/min. Doxycycline hyclate was detected at 280nm and at a 35℃column temperature. The results indicated that the excipients and solvent in the microcapsule could be well separated from the drug under such a designated chromatogram condition. A good linear relationship was found between peak area and the concentration of doxycycline hyclate in the range of 10.0-120.0ug/mL. Linear regression equation was A=18503.14C-9789.27, (r=0.9997.n=7), the average recoveries were between 98.81%and 100.10%(n=5).RSD values of intra-day and inter-day were less than 2%(n=5).It had showed that this method were specific, accurate, reliable, sensitive and applicable for the content and entrapment efficiency determination of doxycycline hyclate microcapsules.Encapsulation efficiency and drug loading were used as the main index of examination, and the orthogonal design was used to optimize the prescripton of doxycycline hyclate-chitosan microcapsules on the base of single factor experiments. Under the optimal prescripton.20.60%and 85.54%were got as the mean drug loading and entrapment efficiency of doxycycline hyclate-chitosan microcapsules.In this work, surface morphology, particle size and particle size distribution, drug encapsulation efficiency, drug loading.stability, drug release kinetics in vitro of drug-loaded microparticles were investigated. SEM observation showed the drug-loaded microparticles exhibited sphere-like shape and average particle size was about l0um with narrow particle size distribution. In vitro release studies revealed that the drug-loaded microparticles substantially improved the sustained-release property. It can be seen that the free doxycycline hyclate rapidly release up to 90%in 3h, drug-loaded microparticles exhibited an accumulative release of 80%after 48h.The results indicated that microencapsulation could highlighted extend release property. And the stability study showed that microencapsulation could enhanced stability of doxycycline hyclate.Doxycycline hyclate solution (A group) and microcapsule suspension liquid (B group)were administrated on health rabbits orally to study the pharmacokinetic of doxycycline hyclate microcapsule. Using doxycycline hyclate solution as a reference, their pharmacokinetic differences were compared. Plasma drug concentration was determined by RP-HPLC. and the pharmacokinetic parameters were analyzed by DAS2.0 pharmacokinetic program. The results showed that data of A, B group was in line with a two-compartment model (weight=1). The main pharmacokinetic parameters and the fitting equation were as follows:A group:Ka was (1.256±0.708)1/h, T1/2a was (1.157±0.526)h. T1/2p was (2.189±0.377)h, AUC(0-∞) was (11.834±0.194)mg/L*h, Cmax was (1.74±0.002)mg/L, Tmax was (3±0.000)h, the fitting equation was C=13.709e-1.256t+7.876e-0.703t-21.585e-0.323t .B group:Ka was (0.204±0.11)1/h. T1/2a was (7.51±2.87)h. T1/2βwas (9.004±1.596)h, AUC(0-∞) was (35.201±0.353)mg/L*h. Cmax was (1.102±0.004)mg/L. Tmax was (12±0.000)h. the fitting equation was C=12.705e-0.204t+12.879e-0.100t-25.584e-0.078tcStudies on the preparation and pharmacokinetics of doxycycline hyclate microcapsules showed the emulsifying crosslinking method was simple and of good reproducibility. and the quality was adjustable. The characteristics of microcapsules were live up to the preparations requirements and had preferable sustained-release, stability, being in favor of prolonging the action time.improving doxycycline hyclate's stability in microcapsule, reduing the administration times. So microcapsulating the doxycycline hyclate has good development and application prospects. |
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