Preparation of composite HRZ/PLGA slow-release microspheres and its drug release characteristics in vitro

English Keywords:Anti-TB drug  Isoniazid  Rifampicin  Pyrazinamide  PLGA  Microsphere  Slow-release

English Abstract:

  【Abstract】 Objectives: To prepare the compound isoniazid(H), rifampicin(R) and pyrazinamide(Z)/polylactic acid-glycolic acid(PLGA)(HRZ/PLGA) sustained release microspheres, and to investigate the physical and chemical properties and slow-release characteristics in vitro. Methods: By using PLGA as the carrier, the HRZ/PLGA microspheres were prepared by emulsifying-solvent evaporation technique under dark conditions, H(40mg), R(60mg), Z(125mg), PLGA(450mg). The characteristics of HRZ/PLGA microspheres were observed under scanning electron microscopy(SEM). The drug-loading and encapsulation rate was evaluated by High performance liquid chromatography(HPLC) in simulated body fluid. The H, R, Z drugs concentration were detected by stripping and HPLC at 3h, 6h, 12h, 1d, 2d, 3d, 6d, 10d, 12d, 15d, 20d, 25d, 30d, 40d, 50d, respectively, in simulated body fluid in vitro and whether greater than minimal inhibitory concentrations(MIC) of 10 times or not was also observed, the average daily release rate and cumulative release rate were calculated by fitted mathematical equations in vitro. Results: HRZ/PLGA microspheres presented as round ball under the SEM, the average particle size was 10.3±4.7μm, drug loading of H, R, Z was (18.02±0.36)%, (22.46±0.24)%, (21.68±0.37)% respectively, encapsulation rate was (54.79±1.13)%, (72.35±0.39)%, (67.21±0.68)% respectively. In vitro the HRZ/PLGA microspheres of cumulative sustained release of three drugs were more than 50% before 12d, the average daily release rate was 5.05%, 4.89%, 6.86%. And at the first 12d, the three drugs of release were basically stable, the average daily release rate was 0.17%, 0.26%, 0.16% respectively. Three drugs concentrations were ten times greater than the MIC even at 50 days. Conclusions: With perfect drug loading and slow release effect, HRZ/PLGA microsphere is an ideal anti-TB drug slow-release complex.