Study On The Rifampicin And Isoniazid-Loaded Microspheres For Lung Targeting

In this thesis,rifampicin(RFP) and isoniazid(IN) were selected as model drugs and Polylactic-co-glycolic acid(PLGA) were used as carriers to prepare biodegradable and biocompatible microspheres(MS) for lung targeting and reducing the adverse effects. Furthermore, the formulas and conditions of preparation , the drug release in vitro and tissue distribution of microspheres were also studied.Ultraviolet-visible spectrophotomatry method was established for determination of the drug loading , encapsulation efficiency of RFP-MS and IN-MS, apparent solubility and the oil/water partition coefficient ; High-performance liquid chromatography(HPLC) method with UV detector was applied to detect drug release in vitro. Dialysis method was employed to examine RFP release in vitro in pH7.4 phosphate buffer solution (PBS)(includingl%Na₂SO₃ ) as the medium and IN release in vitro in pH7.4 PBS as the medium.Analysis methods above were proved to be sensitive, stable, precise and reliable.The apparent solubilities in different media and the partition coefficient in n-octanol/water system at 37℃ were investigated before formulation design. The stability of RFP in pH7.4 PBS(includingl%Na₂SO₃) and IN in pH7.4 PBS was good within 24 hours.RFP-MS and IN-MS with PLGA as carriers were prapared by emulsification-solvent evaporation method and double emulsification-solvent evaporation method,respectively.The influence of formulation and manufacture was studied with particle size, drug loading and encapsulation efficiency as evaluating criterias. Based on the results of single factor experiments, the optimal formulations were verified by orthogonal design.The characteristics of RFP-MS and IN-MS prepared with optimal formulation were investigated and evaluated. The results showed that RFP-MS and IN-MS had good appearance with average particle sizes of 9.76μm and10.24μm,drug loadings of 27.76% and 10.27% , encapsulation efficiencies of 71.61% and 61.53%, respectively.Results of the stability experiments indicated that...