| Ivermectin, which several kinds of its formulations were studied by otherresearchers, has been used as endectocide widely in the world.In present studies, a solvent evaporation process was applied to preparepolymers microsphere containing ivermectin, using 250ml water containing1.5% polyvinyl alcohol (PVA) as water phase, 25ml methylene chloridecontaining ivermectin/polymer (0.43:1) as oil phase. The oil phase was slowlyadded into water phase while stirring at 300~500rpm, after 6~7 hours, thestirring was stopped, the microspheres were collectted. The gelatin microspherewas prepared by emulsion-crosslinking method. The embedding rates of polymerand gelatin microspheres were more than 80% and 2.2%, respectively.The sizes, shapes and surface of microspheres were studied using lightmicroscope and electronic microscope. It was showed that, microsphere'ssurfaces were smooth with many small pores on it, the mean diameters obtainedof lactic/glycolic acid copolymer (PLGA) and polylactic acid (PLA, mw:50000)microspheres were 298, 112, 105 micrometer and 184, 124, 105 micrometer,repectively, when the stirring rate was 300, 400 and 500 rpm. The mean diameterof ethylcellulose (EC) microspheres was 36 μm.In vitro release characteristics of PLGA, PLA and EC microspheres werestudied by using a solution consisted of 95% alcohol and pH7.4 phosphate buffer(4:6) as release medium, the goodness of fit for Higuchi, first order and zeroorder equation was evaluated by the correlative index. The result showed that therelease profile fitted best to zero-order release equation, but the differencesbetween the microspheres with the same mean diameters in another parallelgroups were also observed, microspheres released ivermectin slower than rawcrystalline significantly. The time for 50% of acumulative release for ivermectinraw crystalline, PLA microspheres (184, 124, 105μm), PLGA microspheres (298,112, 105μm) and EC microsphere were 10.6, 213.9, 363.4, 263.5, 1445.7, 281.0and 216.5 hours. The microspheres with larger mean diameter released slowly,but it was not significant when the diameters differred not largely. Burst releasesfor microspheres in 12 hours were 7.41% to 52.54%.Pharmacokinetic studies were carried out in beagle dogs and goats usingHPLC with fluorescence detector for measuring plasma concentration ofivermectin. The plasma concentration versa time curves obtained after singledose S.C. injection of ivermectin in each individual animal was analysed withone or two-compartment open modal, the pharmacokinetic parameters werecalculated. That obtained after injection of microspheres was analysed withnon-compartment modal, AUC were calculated with trapezoidal rule. Theparameters for ivermecin with dose of 0.3mg/kg in dogs, t1/2ka, Tmax, Cmax, t1/2keand AUC0~∞ were 0.17d, 1.33d, 44.31ng/ml, 4.96d, and 323.26ng.d/mlrespectively, in goats, Cmax, AUC and t1/2ke were 11.31ng/ml, 70.29 ng.d/ml and8.73d. The parameters for PLGA (298μm) and PLA (184μm) microspheres withdose 3.0 mg/kg as ivermectin calculated in dogs, Tmax, Cmax, AUC0~t, AUC0~∞,were 0.83d, 56.17ng/ml, 518.18ng.d/ml, 4121.54ng.d/ml and 0.81d, 48.59ng/ml,540.77ng.d/ml, 6860.47ng.d/ml, respectively. The AUC for microspheres weresignificantly larger than that for ivermectin injection. In goats, AUC for PLA,PLGA, EC and gelatin microspheres were 275.91, 408.11, 93.45 and162.84ng.d/ml respectively.The efficacy against nematodes in goats and scabies in pig were studied.The egg reduce percent rate for PLA, PLGA, EC, gelatin microspheres andivermectin injection at the day 14 after treatment were 100%, 100%, 91.1%,42.9% and 100%, and persistent efficacy of PLA and PLGA microspheres wereabout 120 days. The efficacy of PLGA microsphere against scabies in pigs waslike as that of ivermectin injection.The present results suggested that, PLA and PLGA microspheres possessedthe sustained release potency to persist the plasma level of ivermectin above1ng/ml for about 120 days, its efficacy against nematodes was consistent withthe plasma concentration. |
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